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Browse Health
Internist, Nephrologist (kidney)
23 years of experience
Accepting new patients

Credentials

Education ?

Medical School Score Rankings
Harvard University (1989)
  •  
Top 25%

Awards & Distinctions ?

Awards  
One of America's Leading Experts on:
Cardiovascular Diseases
Kidney Diseases
Castle Connolly's Top Doctors™ (2013)
Patients' Choice Award (2015)
On-Time Doctor Award (2015)
Appointments
University of California, San Francisco School of Medicine
Clinical Professor
Stanford Hospital & Clinics
Associations
American Board of Internal Medicine

Affiliations ?

Dr. Chertow is affiliated with 9 hospitals.

Hospital Affiliations

Score

Rankings

  • UCSF Medical Center / Moffitt-Long Hospitals
    521 Parnassus Ave, San Francisco, CA 94143
    •  
    Top 25%
  • Stanford Hospital and Clinics
    300 Pasteur Dr, Stanford, CA 94305
    •  
    Top 25%
  • Mills-Peninsula Health Services
    1783 El Camino Real, Burlingame, CA 94010
    •  
    Top 25%
  • El Camino Hospital
    2500 Grant Rd, Mountain View, CA 94040
    •  
    Top 25%
  • Lucile Salter Packard Children's Hospital @ Stanford
    725 Welch Rd, Palo Alto, CA 94304
    •  
    Top 50%
  • Community Hospital of Los Gatos
    815 Pollard Rd, Los Gatos, CA 95032
    •  
  • Mills Hospital
    100 S San Mateo Dr, San Mateo, CA 94401
  • Stanford University Hospital
  • California Pacific Medical Center- Davies Campus
    45 Castro St, San Francisco, CA 94114
  • Publications & Research

    Dr. Chertow has contributed to 283 publications.
    Title Incidence, Correlates, and Consequences of Acute Kidney Injury in Patients with Pulmonary Arterial Hypertension Hospitalized with Acute Right-side Heart Failure.
    Date May 2012
    Journal Journal of Cardiac Failure
    Excerpt

    Though much is known about the prognostic influence of acute kidney injury (AKI) in left-side heart failure, much less is known about AKI in patients with pulmonary arterial hypertension (PAH).

    Title The Effects of Frequent Nocturnal Home Hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.
    Date February 2012
    Journal Kidney International
    Excerpt

    Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

    Title Association of Self-reported Physical Activity with Laboratory Markers of Nutrition and Inflammation: the Comprehensive Dialysis Study.
    Date February 2012
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    Patients on dialysis maintain extremely low levels of physical activity. Prior studies have demonstrated a direct correlation between nutrition and physical activity but provide conflicting data on the link between inflammation and physical activity. Using a cohort of patients new to dialysis from the Comprehensive Dialysis Study (CDS), we examined associations of self-reported physical activity with laboratory markers of nutrition and inflammation.

    Title Burden on Caregivers As Perceived by Hemodialysis Patients in the Frequent Hemodialysis Network (fhn) Trials.
    Date October 2011
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    Patients with end-stage renal disease often rely on unpaid caregivers to assist them with their daily living and medical needs. We characterized the degree to which patients enrolled in the Frequent Hemodialysis Network (FHN) trials perceived burden on their unpaid caregivers.

    Title Chronic Kidney Disease and Cardiovascular Therapeutics: Time to Close the Evidence Gaps.
    Date October 2011
    Journal Journal of the American College of Cardiology
    Title Intradialytic Hypotension and Vascular Access Thrombosis.
    Date September 2011
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.

    Title Modeled Urea Distribution Volume and Mortality in the Hemo Study.
    Date August 2011
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/V(urea) were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (V(m)), the denominator of equilibrated Kt/V(urea).

    Title The 2011 Esrd Prospective Payment System: an Uncontrolled Experiment.
    Date June 2011
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title Low Level of Self-reported Physical Activity in Ambulatory Patients New to Dialysis.
    Date February 2011
    Journal Kidney International
    Excerpt

    Physical inactivity contributes to the frailty and the decline in function that develops over time among patients with end-stage renal disease. We assessed physical activity among 1547 ambulatory patients new to dialysis in the United States Renal Data System Comprehensive Dialysis Study. We used a self-reporting Human Activity Profile that included Maximal and Adjusted Activity Scores and compared results to established norms by age and gender. Physical activity was found to be extremely low with scores for all age and gender categories below the 5th percentile of healthy individuals and 95% of patients had scores consonant with low fitness. Older age, female gender, diabetes, atherosclerotic disease, and a low level of education were associated with lower activity scores assessed by univariate and multivariable linear regression analysis. Higher serum albumin, creatinine, and lower body mass index, but not hemoglobin levels, were associated with greater physical activity. By multivariable analysis, patients on hemodialysis using a catheter reported lower levels of physical activity compared to those on peritoneal dialysis, hemodialysis using an arteriovenous fistula, or with a graft. Lower Maximal and Adjusted Activity Scores were associated with poor physical function and mental health. Hence, physical activity is distressingly low among patients new to dialysis. Thus, strategies to enhance activity in these patients should be explored.

    Title Updated Comorbidity Assessments and Outcomes in Prevalent Hemodialysis Patients.
    Date February 2011
    Journal Hemodialysis International. International Symposium on Home Hemodialysis
    Excerpt

    When evaluating clinical characteristics and outcomes in patients on hemodialysis, the prevalence and severity of comorbidity may change over time. Knowing whether updated assessments of comorbidity enhance predictive power will assist the design of future studies. We conducted a secondary data analysis of 1846 prevalent hemodialysis patients from 15 US clinical centers enrolled in the HEMO study. Our primary explanatory variable was the Index of Coexistent Diseases score, which aggregates comorbidities, as a time-constant and time-varying covariate. Our outcomes of interest were all-cause mortality, time to first hospitalization, and total hospitalizations. We used Cox proportional hazards regression. Accounting for an updated comorbidity assessment over time yielded a more robust association with mortality than accounting for baseline comorbidity alone. The variation explained by time-varying comorbidity assessments on time to death was greater than age, baseline serum albumin, diabetes, or any other covariates. There was a less pronounced advantage of updated comorbidity assessments on determining time to hospitalization. Updated assessments of comorbidity significantly strengthen the ability to predict death in patients on hemodialysis. Future studies in dialysis should invest the necessary resources to include repeated assessments of comorbidity.

    Title Baseline Characteristics of Participants in the Frequent Hemodialysis Network (fhn) Daily and Nocturnal Trials.
    Date January 2011
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    The annual mortality rate for maintenance hemodialysis patients in the United States is unacceptably high at 15%-20%. In 2004, we initiated the Frequent Hemodialysis Network (FHN) clinical trials. This report presents baseline characteristics of FHN Trial participants and compares them with hemodialysis patients tracked in US Renal Data System (USRDS) data.

    Title Baseline Physical Performance, Health, and Functioning of Participants in the Frequent Hemodialysis Network (fhn) Trial.
    Date January 2011
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Self-reported physical health and functioning and direct measures of physical performance are decreased in hemodialysis patients and are associated with mortality and hospitalization.

    Title Determinants of Cardiac Autonomic Dysfunction in Esrd.
    Date January 2011
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Cardiovascular events are common in patients with ESRD. Whether sympathetic overactivity or vagal withdrawal contribute to cardiovascular events is unclear. We determined the general prevalence and clinical correlates of heart rate variability in patients on hemodialysis.

    Title Can Rescaling Dose of Dialysis to Body Surface Area in the Hemo Study Explain the Different Responses to Dose in Women Versus Men?
    Date January 2011
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    In the Hemodialysis (HEMO) Study, the lower death rate in women but not in men assigned to the higher dose (Kt/V) could have resulted from use of "V" as the normalizing factor, since women have a lower anthropometric V per unit of surface area (V/SA) than men.

    Title Choroidopathy and Kidney Disease: a Case Report and Review of the Literature.
    Date January 2011
    Journal Cases Journal
    Excerpt

    The patient was a 41 year-old Mexican American women who presented with a decrease in visual acuity along with periorbital and peripheral edema. She was diagnosed with bilateral serous retinal detachment and diffuse proliferative lupus nephritis. She improved considerably in hospital after treatment with corticosteroids.

    Title Fluid Accumulation, Recognition and Staging of Acute Kidney Injury in Critically-ill Patients.
    Date January 2011
    Journal Critical Care (london, England)
    Excerpt

    Serum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.

    Title Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury: Penny Wise or Pound Foolish?: Comment on "renal Ultrasonography in the Evaluation of Acute Kidney Injury".
    Date December 2010
    Journal Archives of Internal Medicine
    Title In-center Hemodialysis Six Times Per Week Versus Three Times Per Week.
    Date December 2010
    Journal The New England Journal of Medicine
    Excerpt

    In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.

    Title Blood Pressure Control in Type 2 Diabetes Mellitus.
    Date December 2010
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title Prevalence and Correlates of Cognitive Impairment in Hemodialysis Patients: the Frequent Hemodialysis Network Trials.
    Date November 2010
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Cognitive impairment is common among persons with ESRD, but the underlying mechanisms are unknown. This study evaluated the prevalence of cognitive impairment and association with modifiable ESRD- and dialysis-associated factors in a large group of hemodialysis patients.

    Title Off-label Use of Phosphate Binders in Non-dialysis-dependent Ckd.
    Date November 2010
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title On the Relative Safety of Intravenous Iron Formulations: New Answers, New Questions.
    Date September 2010
    Journal American Journal of Hematology
    Title Infection-related Hospitalizations in Older Patients with Esrd.
    Date September 2010
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Infection is an important cause of hospitalization and death in patients receiving dialysis. Few studies have examined the full range of infections experienced by dialysis patients. The purpose of this study is to examine types, rates, and risk factors for infection in older persons starting dialysis therapy.

    Title Study Design and Subject Baseline Characteristics in the Advance Study: Effects of Cinacalcet on Vascular Calcification in Haemodialysis Patients.
    Date September 2010
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    The ADVANCE (A Randomized Study to Evaluate the Effects of Cinacalcet plus Low-Dose Vitamin D on Vascular Calcification in Subjects with Chronic Kidney Disease Receiving Haemodialysis) Study objective is to assess the effect of cinacalcet plus low-dose active vitamin D versus flexible dosing of active vitamin D on progression of coronary artery calcification (CAC) in haemodialysis patients. We report the ADVANCE Study design and baseline subject characteristics.

    Title The Elderly Patients on Hemodialysis.
    Date August 2010
    Journal Minerva Urologica E Nefrologica = The Italian Journal of Urology and Nephrology
    Excerpt

    Nephrologists care for an increasing number of elderly patients on hemodialysis. As such, an understanding of the overlap among complications of hemodialysis and geriatric syndromes is crucial. This article reviews hemodialysis management issues including vascular access, hypertension, anemia and bone and mineral disorders with an attention towards the distinct medical needs of the elderly. Key concepts of geriatrics frailty, dementia and palliative care are also discussed, as nephrologists frequently participate in decision-making directed toward balancing longevity, functional status and the burden of therapy.

    Title Chronic Kidney Disease in the Urban Poor.
    Date August 2010
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    In the United States, relatively little is known about clinical outcomes of chronic kidney disease (CKD) in vulnerable populations utilizing public health systems. The primary study objectives were to describe patient characteristics, incident ESRD, and mortality in adults with nondialysis-dependent CKD receiving care in the health care safety net.

    Title Vitamin D Deficiency and Frailty in Older Americans.
    Date August 2010
    Journal Journal of Internal Medicine
    Excerpt

    To explore the relation between 25-hydroxyvitamin D deficiency and frailty. Frailty is a multidimensional phenotype that describes declining physical function and a vulnerability to adverse outcomes in the setting of physical stress such as illness or hospitalization. Low serum concentrations of 25-hydroxyvitamin D are known to be associated with multiple chronic diseases such as cardiovascular disease and diabetes, in addition to all cause mortality.

    Title Effects of Reduced Intradialytic Urea Generation Rate and Residual Renal Clearance on Modeled Urea Distribution Volume and Kt/v in Conventional, Daily, and Nocturnal Dialysis.
    Date July 2010
    Journal Seminars in Dialysis
    Excerpt

    Classic urea modeling assumes that both urea generation rate (G) and residual renal urea clearance (Kru) are constant throughout the week, but this may not be true. Reductions in intradialysis G could be caused by lower plasma amino acid levels due to predialysis/intradialysis fasting and also to losses of amino acids into the dialysate. Intradialytic reductions in Kru could be due to lower intravascular volume, blood pressure, or osmotic load. To determine the possible effects of reduced G or Kru during dialysis on the calculation of the volume of distribution (V) and Kt/Vurea, we modeled 3 and 6/week nocturnal, 6/week short daily, and 3/week conventional hemodialysis. A modified 2-pool mathematical model of urea mass balance with a constant time-averaged G was used, but the model was altered to allow adjustment of the ratio of dialytic/interdialytic G (Gd/Gid) and dialytic/total Kru (Krud/Kru) to vary from 1.0 down to near zero. In patients dialyzed six times per week for 400 minutes per session, when Gd/Gid was decreased from 1.0 to 0.05, the predicted urea reduction ratio (URR) increased from 68.9% to 80.2%. To achieve an increased URR of this magnitude under conditions of constant G (Gd/Gid=1.0) required a decrease in modeled urea volume (V) of 36%. At Gd/Gid ratios of 0.8 or 0.6 (corresponding to 20% or 40% reductions in intradialysis G), the modeled URR was increased to 71.0% or 73.3%, causing a 7% or 15% factitious decrease in V. The error was intermediate for the 3/week nocturnal schedule, and was much less pronounced for the 6/week daily and 3/week conventional treatments. Reductions in intradialytic Kru had the opposite effect, lowering the predicted URR and increasing the apparent V, but here the errors were of much lesser amplitude. The results suggest that, particularly for nocturnal dialysis, the standard "constant G" urea kinetic model may need to be modified.

    Title Reexploring Differences Among For-profit and Nonprofit Dialysis Providers.
    Date July 2010
    Journal Health Services Research
    Excerpt

    To determine whether profit status is associated with differences in hospital days per patient, an outcome that may also be influenced by provider financial goals.

    Title Weekend Hospital Admission, Acute Kidney Injury, and Mortality.
    Date June 2010
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Admission to the hospital on weekends is associated with increased mortality for several acute illnesses. We investigated whether patients admitted on a weekend with acute kidney injury (AKI) were more likely to die than those admitted on a weekday. Using the Nationwide Inpatient Sample, a large database of admissions to acute care, nonfederal hospitals in the United States, we identified 963,730 admissions with a diagnosis of AKI between 2003 and 2006. Of these, 214,962 admissions (22%) designated AKI as the primary reason for admission (45,203 on a weekend and 169,759 on a weekday). We used logistic regression models to examine the adjusted odds of in-hospital mortality associated with weekend versus weekday admission. Compared with admission on a weekday, patients admitted with a primary diagnosis of AKI on a weekend had a higher odds of death [adjusted odds ratio (OR) 1.07, 95% confidence interval (CI) 1.02 to 1.12]. The risk for death with admission on a weekend for AKI was more pronounced in smaller hospitals (adjusted OR 1.17, 95% CI 1.03 to 1.33) compared with larger hospitals (adjusted OR 1.07, 95% CI 1.01 to 1.13). Increased mortality was also associated with weekend admission among patients with AKI as a secondary diagnosis across a spectrum of co-existing medical diagnoses. In conclusion, among patients hospitalized with AKI, weekend admission is associated with a higher risk for death compared with admission on a weekday.

    Title Kidney Disease, Hospitalized Hypertension, and Cardiovascular Events: Cause or Consequence?
    Date June 2010
    Journal Circulation
    Title Gfr Estimating Equations, Ckd Prevalence and the Public Health.
    Date June 2010
    Journal Journal of Internal Medicine
    Title Shorter Dialysis Times Are Associated with Higher Mortality Among Incident Hemodialysis Patients.
    Date June 2010
    Journal Kidney International
    Excerpt

    There is an association between hemodialysis session length and mortality independent of the effects of session duration on urea clearance. However, previous studies did not consider changes in session length over time nor did they control for the influence of time-dependent confounding. Using data from a national cohort of 8552 incident patients on thrice-weekly, in-center hemodialysis, we applied marginal structural analysis to determine the association between session length and mortality. Exposure was based on prescribed session length with the outcome being death from any cause. On the 31st day after initiating dialysis, the patients were considered at-risk and remained so until death, censoring, or completion of 1 year on dialysis. On primary marginal structural analysis, session lengths <4 h were associated with a 42% increase in mortality. Sensitivity analyses showed a dose-response relationship between session duration and mortality, and a consistency of findings across prespecified subgroups. Our study suggests that shorter hemodialysis sessions are associated with higher mortality when marginal structural analysis was used to adjust for time-dependent confounding. Further studies are needed to confirm these findings and determine causality.

    Title Standard Kt/vurea: a Method of Calculation That Includes Effects of Fluid Removal and Residual Kidney Clearance.
    Date June 2010
    Journal Kidney International
    Excerpt

    Standard Kt/V(urea) (stdKt/V) is a hypothetical continuous clearance in patients treated with intermittent hemodialysis based on the generation rate of urea nitrogen and the average predialysis urea nitrogen. Previous equations to estimate stdKt/V were derived using a fixed-volume model. To determine the impact of fluid removal as well as residual urea clearance on stdKt/V, we modeled 245 hemodialysis sessions (including conventional 3/week, in-center 6/week, and at-home nocturnal 6/week) in 210 patients enrolled in the Frequent Hemodialysis Network Daily and Nocturnal clinical trials. To examine the role of fluid removal, modeled stdKt/V was compared to stdKt/V estimated from a previously published simplified equation. In a subgroup of 45 sessions with residual urea clearance over 1.5 ml/min, the contribution of residual urea clearance to stdKt/V was measured. For all dialysis schedules, the fixed-volume equation predicted stdKt/V well when both fluid removal and residual urea clearance were set to zero. When fluid removal was included, modeled stdKt/V was slightly underestimated for all three modes of hemodialysis. The shortfall correlated directly with weekly fluid removal and inversely with modeled urea volume. Modeled stdKt/V compressed residual urea clearance to about 70% of its measured value and the fractional downsizing significantly correlated inversely with treatment Kt/V. Our new equation predicted modeled stdKt/V with a high level of accuracy, even when substantial fluid removal and residual urea clearance were present.

    Title Characteristics of Uninsured Americans with Chronic Kidney Disease.
    Date March 2010
    Journal Journal of General Internal Medicine
    Excerpt

    In the United States, public health insurance is available for nearly all persons with end-stage renal disease (ESRD). Little is known about the extent of health insurance coverage for persons with non-dialysis dependent chronic kidney disease (CKD).

    Title Comparison of Methods for Estimating Glomerular Filtration Rate in Critically Ill Patients with Acute Kidney Injury.
    Date March 2010
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    In critically ill patients with acute kidney injury, estimates of kidney function are used to modify drug dosing, adjust nutritional therapy and provide dialytic support. However, estimating glomerular filtration rate is challenging due to fluctuations in kidney function, creatinine production and fluid balance. We hypothesized that commonly used glomerular filtration rate prediction equations overestimate kidney function in patients with acute kidney injury and that improved estimates could be obtained by methods incorporating changes in creatinine generation and fluid balance.

    Title Increased Fluid Intake Does Not Augment Capacity to Lay Down New Collagen in Nursing Home Residents at Risk for Pressure Ulcers: a Randomized, Controlled Clinical Trial.
    Date March 2010
    Journal Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
    Excerpt

    Prevention of pressure ulcers is fundamental to safe care of nursing home residents yet the role of hydration in pressure ulcer prevention has not been systematically examined. This randomized clinical trial was undertaken to determine whether administration of supplemental fluid to nursing home residents at risk for pressure ulcers would enhance collagen deposition, increase estimated total body water, augment subcutaneous tissue oxygenation, and was safe. After a baseline period, 64 subjects were randomized to receive the fluid volume prescribed or additional fluid (prescribed plus 10 mL/kg) for 5 days. Participants' potential to heal as measured with hydroxyproline was low at baseline and did not increase significantly during treatment when additional fluid was systematically provided. Fluid intake increased significantly during treatment. Estimates of total body water and subcutaneous oxygen did not increase, indicating hydration was not improved. Supplemental fluid did not result in overhydration as measured by clinical parameters. Further work is needed to examine the relationship between fluid intake and hydration in nursing home residents as well as the role of hydration in pressure ulcer prevention.

    Title Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease.
    Date March 2010
    Journal The New England Journal of Medicine
    Excerpt

    The U.S. diet is high in salt, with the majority coming from processed foods. Reducing dietary salt is a potentially important target for the improvement of public health.

    Title Preexisting Chronic Kidney Disease: a Potential for Improved Outcomes from Acute Kidney Injury.
    Date February 2010
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear.

    Title The Relationship Between Laboratory-based Outcome Measures and Mortality in End-stage Renal Disease: a Systematic Review.
    Date February 2010
    Journal Hemodialysis International. International Symposium on Home Hemodialysis
    Excerpt

    Despite data that traditional laboratory-based outcome measures in dialysis are improving over time, population-based data indicate that mortality rates are not improving in parallel. With increased focus on performance measures based on laboratory-based outcomes (e.g., hematocrit, albumin, and parathyroid hormone), less emphasis has been placed on other markers, some of which may be stronger predictors of mortality. We performed a systematic review to interpret the predictive value of laboratory-based outcome measures in dialysis. We identified studies with data regarding the predictive value of laboratory-based outcomes for mortality in dialysis. We calculated the sample size-weighted pooled relative risk of death with dichotomized "high" vs. "low" levels of each measure. We rank-ordered predictors by scaling the pooled relative risk of each measure by its pooled standard deviation. There were 5171 titles, of which 128 (representing 44 laboratory-based outcomes) were selected. Nine were significantly associated with mortality, in order of decreasing scaled effect size: (1) tumor necrosis factor-alpha, (2) hematocrit, (3) interleukin-6, (4) troponin T, (5) Kt/V(urea), (6) prealbumin, (7) urea reduction ratio, (8) serum albumin, and (9) C-reactive protein. Other oft-cited measures such as calcium phosphate product and parathyroid hormone were not significantly associated with mortality in pooled analysis. Quality improvement efforts to improve traditional laboratory-based outcomes in end-stage renal disease are necessary, but likely insufficient, to improve overall mortality in dialysis. Renewed consideration of cardiovascular, inflammatory, and nutritional markers that are especially strong predictors of mortality may have important implications for risk stratification and targeted therapeutic interventions.

    Title A Randomized Double-blind Pilot Study of Serum Phosphorus Normalization in Chronic Kidney Disease: a New Paradigm for Clinical Outcomes Studies in Nephrology.
    Date February 2010
    Journal Hemodialysis International. International Symposium on Home Hemodialysis
    Title Medication Errors in Chronic Kidney Disease: One Piece in the Patient Safety Puzzle.
    Date February 2010
    Journal Kidney International
    Excerpt

    Patients with chronic kidney disease (CKD) are at increased risk of harm as a consequence of errors in medical care. Hug and colleagues highlight the significance of adverse drug events in hospitalized patients with CKD. Their findings demonstrate the role adverse drug events play in the safety of patients with CKD and underscore the importance of novel strategies intended to reduce such medical errors.

    Title Intensity of Renal Replacement Therapy in Acute Kidney Injury: Perspective from Within the Acute Renal Failure Trial Network Study.
    Date January 2010
    Journal Critical Care (london, England)
    Excerpt

    Determination of the optimal dose of renal replacement therapy in critically ill patients with acute kidney injury has been controversial. Questions have recently been raised regarding the design and execution of the US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) Study, which demonstrated no improvement in 60-day all-cause mortality with more intensive management of renal replacement therapy. In the present article we present our rationale for these aspects of the design and conduct of the study, including our use of both intermittent and continuous modalities of renal support, our approach to initiation of study therapy and the volume management during study therapy. In addition, the article presents data on hypotension during therapy and recovery of kidney function in the perspective of other studies of renal support in acute kidney injury. Finally, we address the implications of the ATN Study results for clinical practice from the perspective of the study investigators.

    Title Fetuin-a and Change in Body Composition in Older Persons.
    Date January 2010
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    Fetuin-A inhibits the insulin receptor in vitro. Higher serum fetuin-A concentrations are associated with type 2 diabetes longitudinally and greater adiposity in cross-sectional analyses. Whether higher fetuin-A concentrations are associated with accumulation of adiposity over time is unknown.

    Title The Decline in Residual Renal Function in Hemodialysis is Slow and Age Dependent.
    Date December 2009
    Journal Hemodialysis International. International Symposium on Home Hemodialysis
    Excerpt

    Persons on peritoneal dialysis and hemodialysis with preserved residual renal function experience lower mortality rates than those without. Previous studies have shown slower rates of decline of residual renal function for peritoneal dialysis (PD)(2 to 3% decrease/month), compared with hemodialysis (HD)(6 to 7% decrease/month). However, our clinical observations suggested a lower rate of decline in hemodialysis patients.

    Title Coronary and Aortic Calcifications in Patients New to Dialysis.
    Date December 2009
    Journal Hemodialysis International. International Symposium on Home Hemodialysis
    Excerpt

    Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end-stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis.

    Title Dialysis-requiring Acute Renal Failure Increases the Risk of Progressive Chronic Kidney Disease.
    Date December 2009
    Journal Kidney International
    Excerpt

    To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days following hospital discharge. The study encompassed 556,090 adult members of Kaiser Permanente of Northern California hospitalized over an 8 year period, who had pre-admission estimated glomerular filtration rates (eGFR) equivalent to or greater than 45 ml/min/1.73 m(2) and who survived hospitalization. After controlling for potential confounders such as baseline level of eGFR and diabetes status, dialysis-requiring ARF was independently associated with a 28-fold increase in the risk of developing stage 4 or 5 CKD and more than a twofold increased risk of death. Our study shows that in a large, community-based cohort of patients with pre-existing normal or near normal kidney function, an episode of dialysis-requiring ARF was a strong independent risk factor for a long-term risk of progressive CKD and mortality.

    Title Fluid Accumulation, Survival and Recovery of Kidney Function in Critically Ill Patients with Acute Kidney Injury.
    Date November 2009
    Journal Kidney International
    Excerpt

    Fluid accumulation is associated with adverse outcomes in critically ill patients. Here, we sought to determine if fluid accumulation is associated with mortality and non-recovery of kidney function in critically ill adults with acute kidney injury. Fluid overload was defined as more than a 10% increase in body weight relative to baseline, measured in 618 patients enrolled in a prospective multicenter observational study. Patients with fluid overload experienced significantly higher mortality within 60 days of enrollment. Among dialyzed patients, survivors had significantly lower fluid accumulation when dialysis was initiated compared to non-survivors after adjustments for dialysis modality and severity score. The adjusted odds ratio for death associated with fluid overload at dialysis initiation was 2.07. In non-dialyzed patients, survivors had significantly less fluid accumulation at the peak of their serum creatinine. Fluid overload at the time of diagnosis of acute kidney injury was not associated with recovery of kidney function. However, patients with fluid overload when their serum creatinine reached its peak were significantly less likely to recover kidney function. Our study shows that in patients with acute kidney injury, fluid overload was independently associated with mortality. Whether the fluid overload was the result of a more severe renal failure or it contributed to its cause will require clinical trials in which the role of fluid administration to such patients is directly tested.

    Title An Empiric Estimate of the Value of Life: Updating the Renal Dialysis Cost-effectiveness Standard.
    Date November 2009
    Journal Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research
    Excerpt

    Proposals to make decisions about coverage of new technology by comparing the technology's incremental cost-effectiveness with the traditional benchmark of dialysis imply that the incremental cost-effectiveness ratio of dialysis is seen a proxy for the value of a statistical year of life. The frequently used ratio for dialysis has, however, not been updated to reflect more recently available data on dialysis.

    Title Functional Status of Elderly Adults Before and After Initiation of Dialysis.
    Date October 2009
    Journal The New England Journal of Medicine
    Excerpt

    It is unclear whether functional status before dialysis is maintained after the initiation of this therapy in elderly patients with end-stage renal disease (ESRD).

    Title Dialysis: Phosphorus Binders and Survival: Need for Randomized Trials.
    Date September 2009
    Journal Nature Reviews. Nephrology
    Excerpt

    An observational study suggests that administration of phosphorus binders dramatically improves survival rates in patients on incident hemodialysis-even in those without hyperphosphatemia. Randomized clinical trials should drive changes in the relevant clinical practice.

    Title Lost Without Directions: Lessons from the Anemia Debate and the Drive Study.
    Date August 2009
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Growing concerns related to the potential hazards of erythropoiesis stimulating agents have led to downward adjustment in hemoglobin targets for patients with chronic kidney disease, including patients with ESRD on dialysis. These concerns, coupled with economic pressures and shifting cost structures in dialysis funding, have prompted new strategies directed toward the optimal management of anemia, including the call for more liberal use of intravenous iron (1). This article highlights the limited evidence base in support of alternative anemia management strategies and cautions against the injudicious use of iron in this patient population in the absence of sufficient data on long-term safety.

    Title Nonrecovery of Kidney Function and Death After Acute on Chronic Renal Failure.
    Date August 2009
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Relatively little is known about clinical outcomes, especially long-term outcomes, among patients who have chronic kidney disease (CKD) and experience superimposed acute renal failure (ARF; acute on chronic renal failure).

    Title Frailty and Chronic Kidney Disease: the Third National Health and Nutrition Evaluation Survey.
    Date July 2009
    Journal The American Journal of Medicine
    Excerpt

    Frailty is common in the elderly and in persons with chronic diseases. Few studies have examined the association of frailty with chronic kidney disease.

    Title Melamine Nephrotoxicity: an Emerging Epidemic in an Era of Globalization.
    Date July 2009
    Journal Kidney International
    Excerpt

    Recent outbreaks of nephrolithiasis and acute kidney injury among children in China have been linked to ingestion of milk-based infant formula contaminated with melamine. These cases provide evidence in humans for the nephrotoxicity of melamine, which previously had been described only in animals. The consequences of this outbreak are already severe and will likely continue to worsen. Herein we summarize the global impact of the melamine milk contamination, the reemergence of melamine-tainted animal feed, and potential mechanisms of melamine nephrotoxicity. Large-scale epidemiologic studies are necessary to further characterize this disease and to assess its potential long-term sequelae. This epidemic of environmental kidney disease highlights the morbidity associated with adulterated food products available in today's global marketplace and reminds us of the unique vulnerability of the kidney to environmental insults. Melamine is the latest in a growing list of diverse potentially toxic compounds about which nephrologists and other health-care providers responsible for the diagnosis and management of kidney disease must now be aware.

    Title Cum Hoc, Ergo Propter Hoc: Health Disparities Real and Imagined.
    Date June 2009
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Title Is There "cherry Picking" in the Esrd Program? Perceptions from a Dialysis Provider Survey.
    Date June 2009
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Changes in ESRD reimbursement policy, including proposed bundled payment, have raised concern that dialysis facilities may use "cherry picking" practices to attract a healthier, better insured, or more adherent patient population.

    Title The Nexus of Acute Kidney Injury, Chronic Kidney Disease, and World Kidney Day 2009.
    Date June 2009
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Title The Comprehensive Dialysis Study (cds): a Usrds Special Study.
    Date June 2009
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    The Comprehensive Dialysis Study (CDS) aimed to understand factors contributing to physical, functional, and nutritional health status among patients starting dialysis.

    Title Cautious Optimism Concerning Long-term Safety of Kidney Donation.
    Date February 2009
    Journal The New England Journal of Medicine
    Title Cost-effectiveness of Frequent In-center Hemodialysis.
    Date October 2008
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Published evidence suggests that frequent hemodialysis (more than three times per week) for patients with ESRD may improve health-related quality of life and has the potential to increase longevity and reduce hospitalization and other complications. Here, a Monte Carlo simulation model was used to compare varying combinations of in-center hemodialysis frequency (three to six treatments per week) and session length (2 to 4.5 h per session) with regard to unadjusted and quality-adjusted life-years and total lifetime costs for a cohort of 200,000 patients, representing the prevalent ESRD population. The incremental cost-effectiveness ratio was calculated for the various regimens relative to a conventional hemodialysis regimen (three treatments per week, 3.5 h per session). Using conservative assumptions of the potential effects of more frequent hemodialysis on outcomes, most strategies achieved a cost-effectiveness ratio of <$125,000, although all had a cost-effectiveness ratio of >$75,000. The cost-effectiveness ratio increased with the frequency of hemodialysis. More frequent in-center hemodialysis strategies could become cost-neutral if the cost per hemodialysis session could be reduced by 32 to 43%. No other change in model assumptions achieved cost neutrality. In conclusion, given the extraordinarily high costs of the ESRD program, the viability of more frequent hemodialysis strategies depends on significant improvements in the economic model underlying the delivery of hemodialysis.

    Title Management of Acute Kidney Injury in the Intensive Care Unit: a Cost-effectiveness Analysis of Daily Vs Alternate-day Hemodialysis.
    Date October 2008
    Journal Archives of Internal Medicine
    Excerpt

    BACKGROUND: Although evidence suggests that a higher hemodialysis dose and/or frequency may be associated with improved outcomes, the cost-effectiveness of a daily hemodialysis strategy for critically ill patients with acute kidney injury (AKI) is unknown. METHODS: We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of daily hemodialysis, compared with alternate-day hemodialysis, for patients with AKI in the intensive care unit (ICU). We employed a societal perspective with a lifetime analytic time horizon. We modeled the efficacy of daily hemodialysis as a reduction in the relative risk of death on the basis of data reported in the 2004 clinical trial published by Schiffl et al. We performed 1- and 2-way sensitivity analyses across cost, efficacy, and utility input variables. The main outcome measure was cost per quality-adjusted life-year (QALY). RESULTS: In the base case for a 60-year-old man, daily hemodialysis was projected to add 2.14 QALYs and $10,924 in cost. We found that the cost-effectiveness of daily hemodialysis compared with alternate-day hemodialysis was $5084 per QALY gained. The incremental cost-effectiveness ratio became less favorable (>$50,000 per QALY gained) when the maintenance hemodialysis rate of the daily hemodialysis group was varied to more than 27% and when the difference in 14-day postdischarge mortality between the alternatives was varied to less than 0.5%. CONCLUSION: Daily hemodialysis is a cost-effective strategy compared with alternate-day hemodialysis for patients with severe AKI in the ICU.

    Title Combined Therapy with Cinacalcet and Low Doses of Vitamin D Sterols in Patients with Moderate to Severe Secondary Hyperparathyroidism.
    Date September 2008
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Adequate control of all four KDOQI biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca x P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca x P among haemodialysis patients with secondary hyperparathyroidism (sHPT). METHODS: This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160-430 pg/mL) (approximately iPTH 300-800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30-180 mg/day) during an 8-week dose-titration phase to achieve biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L) and efficacy was assessed over 8 weeks. At week 2 of the study, subjects receiving vitamin D sterols had doses reduced to the equivalent of 2 mcg of paricalcitol three times a week or 6 mcg/week. Among the efficacy endpoints were the proportion of subjects with mean biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L), with mean Ca x P <or=55 mg(2)/dL(2) (4.4 mmol(2)/L(2)) and with both simultaneously during the assessment phase. RESULTS: The majority of subjects (n = 375) reached the assessment phase of the study and were included in efficacy analyses; 39 subjects withdrew due to adverse events. Sixty-two percent of subjects achieved the biPTH target, 83% achieved the Ca x P target and 54% reached both targets. Treatment reduced biPTH by 35% (P < 0.0001), calcium by 11% (P < 0.0001), phosphorus by 7% (P < 0.0001) and Ca x P by 17% (P < 0.0001). The proportion of subjects with values for biPTH, for Ca x P and for both biPTH and Ca x P within the target range during the assessment phase did not differ between subjects who received cinacalcet together with vitamin D sterols, and those who received cinacalcet alone. CONCLUSION: Among subjects with moderate to severe sHPT undergoing haemodialysis, combined therapy with cinacalcet and low doses of vitamin D sterols improved achievement of the biochemical targets for CKD-MBD recommended by the KDOQI guidelines.

    Title Trends and Outcomes Associated with Serum Albumin Concentration Among Incident Dialysis Patients in the United States.
    Date September 2008
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    OBJECTIVE AND METHODS: Serum albumin concentrations are associated with mortality, and respond to nutritional and inflammatory states. To explore whether changing demographics and practice patterns in dialysis have influenced serum albumin concentrations, we analyzed trends in serum albumin among incident patients on dialysis from 1995 through 2004. RESULTS: Mean serum albumin concentrations declined significantly over time, even after accounting for changes in age, diabetes, body size, and other factors. Although laboratory assays were not uniform within or across years, serum albumin declined over time, regardless of the reported laboratory lower limit of normal. Moreover, serum albumin retained its potent association with mortality over time. Lower serum albumin was especially hazardous among younger patients and blacks, and was less hazardous among persons with diabetes as a primary cause of kidney disease. CONCLUSIONS: Despite higher body weights and the initiation of dialysis earlier in the course of progressive chronic kidney disease, hypoalbuminemia remains common and hazardous to persons starting dialysis.

    Title Lessons for Successful Study Enrollment from the Veterans Affairs/national Institutes of Health Acute Renal Failure Trial Network Study.
    Date August 2008
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    BACKGROUND AND OBJECTIVES: Design elements of clinical trials can introduce recruitment bias and reduce study efficiency. Trials involving the critically ill may be particularly prone to design-related inefficiencies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Enrollment into the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was systematically monitored. Reasons for nonenrollment into this study comparing strategies of renal replacement therapy in critically ill patients with acute kidney injury were categorized as modifiable or nonmodifiable. RESULTS: 4339 patients were screened; 2744 fulfilled inclusion criteria. Of these, 1034 were ineligible by exclusion criteria. Of the remaining 1710 patients, 1124 (65.7%) enrolled. Impediments to informed consent excluded 21.4% of potentially eligible patients. Delayed identification of potential patients, physician refusal, and involvement in competing trials accounted for 4.4, 2.7, and 2.3% of exclusions. Comfort measures only status, chronic illness, chronic kidney disease, and obesity excluded 11.8, 7.8, 7.6, and 5.9% of potential patients. Modification of an enrollment window reduced the loss of patients from 6.6 to 2.3%. CONCLUSIONS: The Acute Renal Failure Trial Network Study's enrollment efficiency compared favorably with previous intensive care unit intervention trials and supports the representativeness of its enrolled population. Impediments to informed consent highlight the need for nontraditional acquisition methods. Restrictive enrollment windows may hamper recruitment but can be effectively modified. The low rate of physician refusal acknowledges clinical equipoise in the study design. Underlying comorbidities are important design considerations for future trials that involve the critically ill with acute kidney injury.

    Title Higher Serum Creatinine Concentrations in Black Patients with Chronic Kidney Disease: Beyond Nutritional Status and Body Composition.
    Date August 2008
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    BACKGROUND AND OBJECTIVES: Serum creatinine concentrations tend to be higher in black than white individuals and people of other races or ethnicities. These differences have been assumed to be largely related to race-related differences in body composition, especially muscle mass. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a diverse population of hemodialysis patients, we compared mean serum creatinine concentrations in black versus nonblack patients, adjusting for case mix (age, gender, diabetes, and dialysis vintage), body size (height, weight), laboratory parameters of nutritional status (albumin, predialysis blood urea nitrogen, transferrin, phosphorus, glucose), dialysis dosage (urea reduction ratio), and parameters of bioelectrical impedance (resistance and reactance), proxies for body composition. RESULTS: Adjusted mean serum creatinine concentrations were significantly higher in black versus nonblack patients (11.7 versus 10.0 mg/dl; P < 0.0001). Black patients were roughly four-fold more likely to have a serum creatinine concentration >10 mg/dl and six-fold more likely to have a serum creatinine concentration >15 mg/dl. Higher serum creatinine concentrations were associated with a lower relative risk for death (0.93; 95% confidence interval 0.88 to 0.98 per mg/dl); the association was slightly more pronounced among nonblack patients. CONCLUSIONS: Serum creatinine concentrations are significantly higher in black compared with nonblack hemodialysis patients; these differences are not readily explained by differences in nutritional status or body composition.

    Title The Risk of Acute Renal Failure in Patients with Chronic Kidney Disease.
    Date July 2008
    Journal Kidney International
    Excerpt

    Few studies have defined how the risk of hospital-acquired acute renal failure varies with the level of estimated glomerular filtration rate (GFR). It is also not clear whether common factors such as diabetes mellitus, hypertension and proteinuria increase the risk of nosocomial acute renal failure independent of GFR. To determine this we compared 1,746 hospitalized adult members of Kaiser Permanente Northern California who developed dialysis-requiring acute renal failure with 600,820 hospitalized members who did not. Patient GFR was estimated from the most recent outpatient serum creatinine measurement prior to admission. The adjusted odds ratios were significantly and progressively elevated from 1.95 to 40.07 for stage 3 through stage 5 patients (not yet on maintenance dialysis) compared to patients with estimated GFR in the stage 1 and 2 range. Similar associations were seen after controlling for inpatient risk factors. Pre-admission baseline diabetes mellitus, diagnosed hypertension and known proteinuria were also independent risk factors for acute kidney failure. Our study shows that the propensity to develop in-hospital acute kidney failure is another complication of chronic kidney disease whose risk markedly increases even in the upper half of stage 3 estimated GFR. Several common risk factors for chronic kidney disease also increase the peril of nosocomial acute kidney failure.

    Title Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury.
    Date July 2008
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND: The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS: We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS: Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS: Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

    Title Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury.
    Date June 2008
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.

    Title High-molecular Weight Iron Dextran: a Wolf in Sheep's Clothing?
    Date May 2008
    Journal Journal of the American Society of Nephrology : Jasn
    Title Toward the Promise of Renal Replacement Therapy.
    Date May 2008
    Journal Journal of the American Society of Nephrology : Jasn
    Title Race and Mortality After Acute Renal Failure.
    Date February 2008
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Black patients receiving dialysis for end-stage renal disease in the United States have lower mortality rates than white patients. Whether racial differences exist in mortality after acute renal failure is not known. We studied acute renal failure in patients hospitalized between 2000 and 2003 using the Nationwide Inpatient Sample and found that black patients had an 18% (95% confidence interval [CI] 16 to 21%) lower odds of death than white patients after adjusting for age, sex, comorbidity, and the need for mechanical ventilation. Similarly, among those with acute renal failure requiring dialysis, black patients had a 16% (95% CI 10 to 22%) lower odds of death than white patients. In stratified analyses of patients with acute renal failure, black patients had significantly lower adjusted odds of death than white patients in settings of coronary artery bypass grafting, cardiac catheterization, acute myocardial infarction, congestive heart failure, pneumonia, sepsis, and gastrointestinal hemorrhage. Black patients were more likely than white patients to be treated in hospitals that care for a larger number of patients with acute renal failure, and black patients had lower in-hospital mortality than white patients in all four quartiles of hospital volume. In conclusion, in-hospital mortality is lower for black patients with acute renal failure than white patients. Future studies should assess the reasons for this difference.

    Title Kidney Dysfunction and Fatal Cardiovascular Disease--an Association Independent of Atherosclerotic Events: Results from the Health, Aging, and Body Composition (health Abc) Study.
    Date January 2008
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Impaired kidney function has been associated with increased risk for death, myocardial infarction, stroke, and heart failure in high-risk populations. We evaluated whether impaired kidney function predicted risk of fatal cardiovascular disease independent of prevalent and incident cardiovascular events. METHODS: The Health, Aging, and Body Composition study is a cohort of well-functioning, elderly participants aged 70 to 79 years at entry. We measured serum cystatin C and creatinine from baseline plasma samples of 3044 participants and followed them over 6 years, examining the associations among kidney function, cardiovascular death, and incident cardiovascular events. Cystatin C was categorized as low (< 0.84 mg/L), medium (0.84-1.18 mg/L), or high (> or = 1.19 mg/L); serum creatinine (cutoff value of > or = 1.3 in women and > or = 1.5 in men) and estimated glomerular filtration rate (eGFR; greater and less than 60 mL/min per 1.73 m2) were dichotomized. RESULTS: During follow-up, 242 cardiovascular deaths occurred, of which 69 were in participants without prior cardiovascular events; 294 incident cardiovascular events occurred including 135 myocardial infarctions and 163 strokes. Higher cystatin C concentrations were significantly associated with cardiovascular death (adjusted hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.05-2.76 for the medium cystatin C group; and HR 2.24, 95% CI 1.30-3.86 for the high cystatin C group, relative to the low cystatin C group). The point estimate was of greater magnitude in the analysis that excluded prevalent cardiovascular disease (adjusted HR 2.68, 95% CI 0.94-7.70 for the medium cystatin C group; and HR 4.91, 95% CI, 1.55-15.54 for the high cystatin C group). Elevated creatinine levels (adjusted HR 1.54, 95% CI 1.02-2.33, and HR 2.28, 95% CI 1.10-4.73 among participants without a history of cardiovascular disease) were also associated with cardiovascular death. No significant association was found between low eGFR and cardiovascular death. In addition, cystatin C, low eGFR, or elevated creatinine levels were not associated with other cardiovascular events. CONCLUSION: Impaired kidney function is a strong predictor of cardiovascular death, particularly among participants without prior history of cardiovascular disease.

    Title Predictive and Pathogenetic Value of Plasma Biomarkers for Acute Kidney Injury in Patients with Acute Lung Injury.
    Date December 2007
    Journal Critical Care Medicine
    Excerpt

    OBJECTIVE: To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury. DESIGN: Secondary data analysis from a multicenter, randomized clinical trial. SETTING: Intensive care units in ten university medical centers. PATIENTS: A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial. INTERVENTIONS: Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design. MEASUREMENTS AND MAIN RESULTS: We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003). CONCLUSIONS: Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury.

    Title Significance of Frailty Among Dialysis Patients.
    Date December 2007
    Journal Journal of the American Society of Nephrology : Jasn
    Title Chronic Kidney Disease Mineral Bone Disorder and Health-related Quality of Life Among Incident End-stage Renal-disease Patients.
    Date October 2007
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    OBJECTIVE: Our objective was to determine the extent to which chronic kidney disease mineral bone disorder (CKD-MBD) is associated with health-related quality of life among incident dialysis patients. DESIGN: This study's design was a cross-sectional analysis. SETTING: This was part of the United States Renal Data System Dialysis Morbidity and Mortality Study (DMMS), Wave 2. PATIENTS: The patients comprised 2590 adult participants in DMMS Wave 2, for whom quality of life and laboratory data were available. METHODS: We stratified patients according to their serum concentrations of phosphorus, calcium, and parathyroid hormone (PTH), and compared health-related quality of life as a function of these indicators in analyses adjusted for demographic, clinical, and other laboratory variables. MAIN OUTCOME MEASURES: Main outcome measures included Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and the Symptom score of the Kidney Disease Quality of Life. RESULTS: Both high and low serum phosphorus concentrations were associated with lower PCS scores (-1.25 to -1.48 points compared with the reference category), as was low PTH (-1.49 points). Low serum phosphorus was associated with more severe symptoms of kidney disease (-3.88 points), but there were no associations between high phosphorus or either extreme of PTH and the Symptom score. Serum calcium concentration and the calcium x phosphorus product were unassociated with PCS or Symptom scores. There were no associations among phosphorus, calcium, or PTH and MCS. Analyses simultaneously controlling for serum phosphorus, calcium, and PTH showed similar results. CONCLUSION: High and low serum phosphorus and low PTH are associated with slightly poorer self-reported physical functioning. Clinical trials will be necessary to determine whether and to what extent improvement in health status may occur with the correction of selected disorders of mineral metabolism.

    Title Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (evolve): Rationale and Design Overview.
    Date September 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    BACKGROUND AND OBJECTIVES: The dramatically high rates of mortality and cardiovascular morbidity observed among dialysis patients highlights the importance of identifying and implementing strategies to lower cardiovascular risk in this population. Results from clinical trials undertaken thus far, including trials on lipid reduction, normalization of hematocrit, and increased dialysis dosage, have been unsuccessful. Available data indicate that abnormalities in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism alone or the therapeutic measures used to manage secondary hyperparathyroidism, are associated with an increased risk for death and cardiovascular events. However, no prospective trials have evaluated whether interventions that modify these laboratory parameters result in a reduction in adverse cardiovascular outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events is a global, phase 3, double-blind, randomized, placebo-controlled trial evaluating the effects of cinacalcet on mortality and cardiovascular events in hemodialysis patients with secondary hyperparathyroidism. Approximately 3800 patients from 22 countries will be randomly assigned to cinacalcet or placebo. Flexible use of traditional therapies will be permitted. The primary end point is the composite of time to all-cause mortality or first nonfatal cardiovascular event (myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular disease, including lower extremity revascularization and nontraumatic amputation). RESULTS: The study will be event driven (terminated at 1882 events) with an anticipated duration of approximately 4 yr. CONCLUSIONS: Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events will determine whether management of secondary hyperparathyroidism with cinacalcet reduces the risk for mortality and cardiovascular events in hemodialysis patients.

    Title Rise of Pay for Performance: Implications for Care of People with Chronic Kidney Disease.
    Date September 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Many health care providers and policy makers believe that health care financing systems fail to reward high-quality care. In recent years, federal and private payers have begun to promote pay for performance, or value-based purchasing, initiatives to raise the quality of care. This report describes conceptual issues in the design and implementation of pay for performance for chronic kidney disease and ESRD care. It also considers the implications of recent ESRD payment policy changes on the broader goals of pay for performance. Congressionally mandated bundle payment demonstration for dialysis, newly implemented case-mix adjustment of the composite rate, and G codes for the monthly capitation payment are important opportunities to understand facility and provider behavior with particular attention to patient selection and treatment practices. Well-designed payment systems will reward quality care for patients while maintaining appropriate accountability and fairness for health care providers.

    Title Community-based Incidence of Acute Renal Failure.
    Date September 2007
    Journal Kidney International
    Excerpt

    There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and confounded by variations in threshold and the rate of hospitalization. Earlier studies relied on diagnostic codes to identify non-dialysis requiring ARF. These underestimated disease incidence since the codes have low sensitivity. Here we quantified the incidence of non-dialysis and dialysis-requiring ARF among members of a large integrated health care delivery system - Kaiser Permanente of Northern California. Non-dialysis requiring ARF was identified using changes in inpatient serum creatinine values. Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from 322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5 per 100,000 person-years. ARF was more common in men and among the elderly, although those aged 80 years or more were less likely to receive acute dialysis treatment. We conclude that the use of serum creatinine measurements to identify cases of non-dialysis requiring ARF resulted in much higher estimates of disease incidence compared with previous studies. Both dialysis-requiring and non-dialysis requiring ARFs are becoming more common. Our data underscore the public health importance of ARF.

    Title The Case Against Calcium-based Phosphate Binders.
    Date September 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Disturbances of mineral metabolism are associated with significant morbidity and mortality in patients with chronic kidney disease. Unfortunately, some of the treatments for these disturbances also have been found to be associated with morbidity. More recently, there is increasing evidence in the form of prospective, randomized trials that the use of calcium-based phosphate binders contributes to progressive coronary artery and aorta calcification compared with the non-calcium-containing binder sevelamer. Moreover, there is compelling biologic plausibility that hyperphosphatemia and excess exogenous calcium administration can accelerate vascular calcification. Unfortunately, there is no bedside test that can determine whether there is a dose of calcium salts (either as maintenance or as cumulative dose) that can be administered safely, and, unfortunately, the serum calcium concentration does not reflect calcium balance. Therefore, calcium-based phosphate binders should be avoided in many, if not most, patients who are undergoing dialysis.

    Title Evolving Practices in Critical Care and Potential Implications for Management of Acute Kidney Injury.
    Date September 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Title Cinacalcet Hydrochloride (sensipar) in Hemodialysis Patients on Active Vitamin D Derivatives with Controlled Pth and Elevated Calcium X Phosphate.
    Date August 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Active vitamin D derivatives attenuate the severity of secondary hyperparathyroidism but often increase serum calcium (Ca) and phosphorus (P) as a result of enhanced intestinal absorption. The calcimimetic cinacalcet HCl lowers parathyroid hormone (PTH) and tends to decrease Ca x P. A 16-wk, open-label clinical trial was conducted in adult hemodialysis patients who had controlled PTH (biointact PTH [biPTH] 80 to 160 pg/ml) and elevated Ca x P (> 55 mg2/dl2) and were receiving paricalcitol > 6 microg/wk (or an equipotent dose of an alternative active vitamin D derivative). At the start of the study, active vitamin D derivatives were decreased to a mean equivalent dose of paricalcitol 6 microg/wk, and cinacalcet was titrated from 30 mg/d to a maximum possible dose of 180 mg/d. Of the 72 study patients, 53 (74%) completed 8 wk of dose titration with cinacalcet. In response to cinacalcet, the following mean percentage changes were observed: biPTH, -1.8%; Ca, -9.7% (P < 0.0001), phosphorus, -11.1% (P < 0.0001), and Ca x P, -20.1% (P < 0.0001). At the end of the study, approximate Kidney Disease Outcomes Quality Initiative targets for biPTH (< or = 160 pg/ml) were achieved in 85% (45 of 53) of patients and for Ca x P (< or = 55 mg2/dl2) in 72% (38 of 53) of patients. Concurrent achievement of both targets occurred in 47% (25 of 53) of patients. In this open-label clinical trial, hemodialysis patients who had controlled PTH but elevated Ca x P and were taking moderate- to high-dose active vitamin D derivatives achieved improved control of mineral metabolism with a combination of low-dose active vitamin D derivatives and cinacalcet. The long-term effects of this treatment regimen on clinical outcomes should be tested prospectively.

    Title Strategies for Successful Patient Oriented Research: Why Did I (not) Get Funded?
    Date August 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Writing grants that are subsequently funded is an integral part of the process of patient-oriented research. A catalogue of common deficiencies that are identified in the grant review process can yield valuable insights into the process of grant writing. This article provides the authors' opinion on the common pitfalls in the current patient-oriented research applications that if identified before submission can lead to a stronger application. The authors participated in the review of clinical research grants to the National Kidney Foundation and catalogued the weaknesses of the grants that were reviewed and discussed. The top five reasons identified with grants were problems with study design (76%); statistical issues (34%); general issues such as ownership of the work, mentor, and environment (29%); weak hypothesis (24%); and problems with the research question, such as novelty or lack of creation of new data (24%). Patient-oriented research grants that have strong mentoring, are hypothesis driven, and have a strong study design that addresses sample size, analysis, and confounding factors have an increased chance of yielding high-quality research and, therefore, successful funding.

    Title Timing of Initiation of Dialysis in Critically Ill Patients with Acute Kidney Injury.
    Date August 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Among critically ill patients, acute kidney injury (AKI) is a relatively common complication that is associated with an increased risk for death and other complications. To date, no treatment has been developed to prevent or attenuate established AKI. Dialysis often is required, but the optimal timing of initiation of dialysis is unknown. Data from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter observational study of AKI, were analyzed. Among 243 patients who did not have chronic kidney disease and who required dialysis for severe AKI, we examined the risk for death within 60 d from the diagnosis of AKI by the blood urea nitrogen (BUN) concentration at the start of dialysis (BUN < or = 76 mg/dl in the low degree of azotemia group [n = 122] versus BUN > 76 mg/dl in the high degree of azotemia group [n = 121]). Standard Kaplan-Meier product limit estimates, proportional hazards (Cox) regression methods, and a propensity score approach were used to account for selection effects. Crude survival rates were slightly lower for patients who started dialysis at higher BUN concentrations, despite a lesser burden of organ system failure. Adjusted for age, hepatic failure, sepsis, thrombocytopenia, and serum creatinine and stratified by site and initial dialysis modality, the relative risk for death that was associated with initiation of dialysis at a higher BUN was 1.85 (95% confidence interval 1.16 to 2.96). Further adjustment for the propensity score did not materially alter the association (relative risk 1.97; 95% confidence interval 1.21 to 3.20). Among critically ill patients with AKI, initiation of dialysis at higher BUN concentrations was associated with an increased risk for death. Although the results could reflect residual confounding by severity of illness, they provide a rationale for prospective testing of alternative dialysis initiation strategies in critically ill patients with severe AKI.

    Title Studying the Prevention of Acute Kidney Injury: Lessons from an 18th-century Mathematician.
    Date August 2007
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Title The Incidence and Prognostic Significance of Acute Kidney Injury.
    Date June 2007
    Journal Current Opinion in Nephrology and Hypertension
    Excerpt

    PURPOSE OF REVIEW: Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. This review summarizes the major epidemiologic studies that have informed our understanding of the incidence and prognostic significance of acute kidney injury. RECENT FINDINGS: Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury, including the incidence, prognostic significance and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g. following exposure to intravenous contrast, sepsis and major surgery) have provided further details into this heterogeneous syndrome. SUMMARY: In light of the increasing incidence and prognostic significance of acute kidney injury, new strategies for prevention and treatment are desperately needed.

    Title Association of Fetuin-a with Mitral Annular Calcification and Aortic Stenosis Among Persons with Coronary Heart Disease: Data from the Heart and Soul Study.
    Date June 2007
    Journal Circulation
    Excerpt

    BACKGROUND: Fetuin-A is a multifunctional hepatic secretory protein that inhibits dystrophic vascular and valvular calcification. Lower serum fetuin-A concentrations are associated with valvular calcification in persons with end-stage renal disease. Whether fetuin-A is associated with valvular calcification in other patient populations is unknown. METHODS AND RESULTS: We evaluated the associations among serum fetuin-A concentrations, mitral annular calcification, and aortic stenosis in 970 ambulatory persons with coronary heart disease and without severe kidney disease. The presence or absence of mitral annular calcification and aortic stenosis was determined by transthoracic echocardiography. The subjects' mean age was 66 years; 81% were men; 189 (20%) had mitral annular calcification; and 79 (8%) had aortic stenosis. Participants were categorized by tertiles of fetuin-A concentrations. Those within the highest fetuin-A tertile had significantly lower odds of mitral annular calcification compared with the lowest tertile (adjusted odds ratio, 0.47; 95% confidence interval, 0.29 to 0.77; P=0.002); this association was similar regardless of diabetes status (P for interaction=0.34). In contrast, the association of fetuin-A with aortic stenosis was modified by the presence or absence of diabetes mellitus (P for interaction=0.03). Among participants without diabetes, the highest fetuin-A tertile had a significantly lower odds of aortic stenosis compared with the lowest tertile (adjusted odds ratio, 0.37; 95% confidence interval, 0.15 to 0.92; P=0.03), whereas among participants with diabetes, no statistically significant association was observed between fetuin-A and aortic stenosis (adjusted odds ratio, 1.49; 95% confidence interval, 0.48 to 4.63; P=0.49). CONCLUSIONS: Among persons with coronary heart disease, we observed an inverse association of fetuin-A and mitral annular calcification. An inverse association also was observed between fetuin-A and aortic stenosis among participants without diabetes mellitus. Fetuin-A may represent an important inhibitor of dystrophic calcification in persons with coronary heart disease.

    Title Survival by Dialysis Modality in Critically Ill Patients with Acute Kidney Injury.
    Date June 2007
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Among critically ill patients, acute kidney injury (AKI) requiring dialysis is associated with mortality rates generally in excess of 50%. Continuous renal replacement therapies (CRRT) often are recommended and widely used, although data to support its superiority over intermittent hemodialysis (IHD) are lacking. Data from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter observational study of AKI, were analyzed. Among 398 patients who required dialysis, the risk for death within 60 d was examined by assigned initial dialysis modality (CRRT [n = 206] versus IHD [n = 192]) using standard Kaplan-Meier product limit estimates, proportional hazards ("Cox") regression methods, and a propensity score approach to account for selection effects. Crude survival rates were lower for patients who were treated with CRRT than IHD (survival at 30 d 45 versus 58%; P = 0.006). Adjusted for age, hepatic failure, sepsis, thrombocytopenia, blood urea nitrogen, and serum creatinine and stratified by site, the relative risk for death associated with CRRT was 1.82 (95% confidence interval 1.26 to 2.62). Further adjustment for the propensity score did not materially alter the association (relative risk 1.92; 95% confidence interval 1.28 to 2.89). Among critically ill patients with AKI, CRRT was associated with increased mortality. Although the results could reflect residual confounding by severity of illness, these data provide no evidence for a survival benefit afforded by CRRT. Larger, prospective, randomized clinical trials to compare CRRT and IHD in severe AKI are needed.

    Title End Stage Renal Disease.
    Date May 2007
    Journal Clinical Evidence
    Title Fetuin-a and Kidney Function in Persons with Coronary Artery Disease--data from the Heart and Soul Study.
    Date April 2007
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Fetuin-A is a serum protein that inhibits ectopic vascular calcification and is present in lower concentrations in end-stage renal disease than in healthy controls. Whether fetuin-A concentrations are also lower in the setting of mild-to-moderate chronic kidney disease (CKD) is unknown. METHODS: We evaluated the associations of several parameters of kidney function including measured 24 h urinary creatinine clearance (CrCl), estimated glomerular filtration rate (GFR) by the Mayo Clinic quadratic GFR equation (qGFR), serum cystatin-C concentrations, and urinary albumin-to-creatinine ratio with serum fetuin-A concentrations in 970 outpatients with coronary artery disease. We used general linear models to determine the adjusted mean fetuin-A concentrations within each kidney function category. RESULTS: The mean age of the study sample was 67 years, 82% were male, 71% had hypertension and 26% had diabetes mellitus. In adjusted analysis, we observed no significant differences in mean fetuin-A concentrations across groups defined by CrCl, qGFR, or albumin-to-creatinine ratio groups. For example, adjusted mean fetuin-A concentrations were 0.66 g/l in participants with CrCl > 90, 60-90 and 45-60 ml/min/1.73 m(2), and 0.65 g/l in participants with CrCl < 45 ml/min/1.73 m(2). Higher serum cystatin-C (indicating worse kidney function) was associated with higher adjusted mean serum fetuin-A concentrations (lowest quartile 0.62 g/l, highest quartile 0.68 g/l; P for trend <0.001). CONCLUSIONS: Among ambulatory patients with coronary artery disease, there is no evidence that mild-to-moderate CKD is associated with lower concentrations of serum fetuin-A compared with persons with normal renal function. The mechanisms explaining the association between CKD and vascular calcification remain elusive.

    Title Frequent Hemodialysis Network (fhn) Randomized Trials: Study Design.
    Date March 2007
    Journal Kidney International
    Excerpt

    Observational studies suggest improvements with frequent hemodialysis (HD), but its true efficacy and safety remain uncertain. The Frequent Hemodialysis Network Trials Group is conducting two multicenter randomized trials of 250 subjects each, comparing conventional three times weekly HD with (1) in-center daily HD and (2) home nocturnal HD. Daily HD will be delivered for 1.5-2.75 h, 6 days/week, with target eK(t)/V(n) > or = 0.9/session, whereas nocturnal HD will be delivered for > or = 6 h, 6 nights/week, with target stdK(t)/V of > or = 4.0/week. Subjects will be followed for 1 year. The composite of mortality with the 12-month change in (i) left ventricular mass index (LVMI) by magnetic resonance imaging, and (ii) SF-36 RAND Physical Health Composite (PHC) are specified as co-primary outcomes. The seven main secondary outcomes are between group comparisons of: change in LVMI, change in PHC, change in Beck Depression Inventory score, change in Trail Making Test B score, change in pre-HD serum albumin, change in pre-HD serum phosphorus, and rates of non-access hospitalization or death. Changes in blood pressure and erythropoiesis will also be assessed. Safety outcomes will focus on vascular access complications and burden of treatment. Data will be obtained on the cost of delivering frequent HD compared to conventional HD. Efforts will be made to reduce bias, including blinding assessment of subjective outcomes. Because no large-scale randomized trials of frequent HD have been previously conducted, the first year has been designated a Vanguard Phase, during which feasibility of randomization, ability to deliver the interventions, and adherence will be evaluated.

    Title Phosphorus Balance and Mineral Metabolism with 3 H Daily Hemodialysis.
    Date March 2007
    Journal Kidney International
    Excerpt

    Poor control of mineral metabolism is independently associated with mortality in patients receiving hemodialysis. We analyzed data from a 12-month, prospective, non-randomized, controlled study of daily hemodialysis (DHD) (six sessions/week 3 h each) (n=26) vs conventional hemodialysis (CHD) (three sessions/week 4 h each) (n=51) for achievement of mineral metabolism goals and we performed a substudy of weekly dialytic phosphorus removal in DHD vs CHD. Phosphorus control was superior in the DHD group (% change from baseline to end-of-study -27+/-30% vs +7%+/-35% in the CHD group, P=0.0001). Percentage of patients using phosphate binders decreased from 77 to 40% among subjects on DHD, whereas these parameters did not change (76 vs 77%) in the CHD group (P=0.03 by Breslow-Day test for homogeneity of the odds ratios). Weekly mean phosphorus removal was higher in the DHD group (2452+/-720 mg/week vs 1572+/-366 mg/week, P=0.04). Mean normalized protein catabolic rate increased (0.90+/-0.43-1.22+/-0.26 g/kg/day, P=0.0013). DHD was also associated with an increase in the percent of subjects achieving three or more mineral metabolism goals (for phosphorus, calcium x phosphorus and parathyroid hormone) (15 vs 46%, P=0.046). In conclusion, DHD improves phosphorus control by increasing dialytic phosphorus removal while maintaining nutritional status and reducing the use of phosphate binders. The net effect allows for improved achievement of mineral metabolism goals.

    Title Octogenarians and Nonagenarians Starting Dialysis in the United States.
    Date February 2007
    Journal Annals of Internal Medicine
    Excerpt

    BACKGROUND: The elderly constitute the fastest-growing segment of the end-stage renal disease (ESRD) population, but the epidemiology and outcomes of dialysis among the very elderly, that is, those 80 years of age and older, have not been previously examined at a national level. OBJECTIVE: To describe recent trends in the incidence and outcomes of octogenarians and nonagenarians starting dialysis. DESIGN: Observational study. SETTING: U.S. Renal Data System, a comprehensive, national registry of patients with ESRD. PARTICIPANTS: Octogenarians and nonagenarians initiating dialysis between 1996 and 2003. MEASUREMENTS: Rates of dialysis initiation and survival. RESULTS: The number of octogenarians and nonagenarians starting dialysis increased from 7054 persons in 1996 to 13,577 persons in 2003, corresponding to an average annual increase in dialysis initiation of 9.8%. After we accounted for population growth, the rate of dialysis initiation increased by 57% (rate ratio, 1.57 [95% CI, 1.53 to 1.62]) between 1996 and 2003. One-year mortality for octogenarians and nonagenarians after dialysis initiation was 46%. Compared with octogenarians and nonagenarians initiating dialysis in 1996, those starting dialysis in 2003 had a higher glomerular filtration rate and less morbidity related to chronic kidney disease but no difference in 1-year survival. Clinical characteristics strongly associated with death were older age, nonambulatory status, and more comorbid conditions. LIMITATIONS: Survival of patients with incident ESRD who did not begin dialysis could not be assessed. CONCLUSIONS: The number of octogenarians and nonagenarians initiating dialysis has increased considerably over the past decade, while overall survival for patients on dialysis remains modest. Estimates of prognosis based on patient characteristics, when considered in conjunction with individual values and preferences, may aid in dialysis decision making for the very elderly.

    Title Association of Cystatin C with Mortality, Cardiovascular Events, and Incident Heart Failure Among Persons with Coronary Heart Disease: Data from the Heart and Soul Study.
    Date February 2007
    Journal Circulation
    Excerpt

    BACKGROUND: Serum creatinine and related estimating equations predict cardiovascular events and mortality among persons with coronary heart disease (CHD). Cystatin C is a novel and sensitive endogenous marker of kidney function. Whether cystatin C concentrations are associated with adverse events among ambulatory persons with CHD is unknown. METHODS AND RESULTS: Nine hundred ninety ambulatory persons with CHD were categorized into quartiles of serum cystatin C at inception, with < or = 0.91 mg/L constituting the lowest quartile (I) and > or = 1.30 mg/L constituting the highest (IV). Cox proportional hazards models evaluated time to all-cause mortality, cardiovascular events (composite of CHD death, myocardial infarction, and stroke), and incident heart failure. After a median follow-up of 37 months, 132 participants (13%) died, 101 (10%) had cardiovascular events, and 57 (7%) had incident heart failure. Compared with participants in the lowest cystatin C quartile, those in the highest quartile were at increased risk of all-cause mortality (hazard ratio, 3.6; 95% CI, 1.8 to 7.0), cardiovascular events (hazard ratio, 2.0; 95% CI, 1.0 to 3.8), and incident heart failure (hazard ratio, 2.6; 95% CI, 1.0 to 6.9) in analyses adjusted for traditional cardiovascular risk factors. Cystatin C in the highest quartile predicted similar risk for these outcomes among participants with lower (< or = 60 mL/min per 1.73 m2) or higher estimated glomerular filtration rate and among participants with or without microalbuminuria. CONCLUSIONS: High cystatin C concentrations predict substantial increased risks of all-cause mortality, cardiovascular events, and incident heart failure among ambulatory persons with CHD. This risk is not completely captured by measures of kidney function routinely used in clinical practice.

    Title Less-than-subtotal Parathyroidectomy Increases the Risk of Persistent/recurrent Hyperparathyroidism After Parathyroidectomy in Tertiary Hyperparathyroidism After Renal Transplantation.
    Date January 2007
    Journal Surgery
    Excerpt

    BACKGROUND: The optimal surgical approach for tertiary hyperparathyroidism (HPT) after kidney transplantation is unknown. Existing studies are limited by small sample size, lack of adjustment for kidney function, and no long-term follow-up. METHODS: We retrospectively analyzed 74 patients with tertiary HPT who underwent parathyroidectomy at two centers since 1978. Persistent HPT was defined as parathyroid hormone (PTH) concentrations in excess of the K/DOQI target range for the corresponding estimated creatinine clearance (eCrCl). RESULTS: Seventy-four patients had 83 operations (72 subtotal and 11 less-than-subtotal parathyroidectomies). Mean follow-up time was 5.4 +/- 4.7 years. Calcium concentrations decreased significantly after parathyroidectomy (2.83 vs 2.28 mmol/L, P < 0.001), as did eCrCl (54.5 vs 44.9 mL/min, P < 0.001) and PTH (382 vs 132 pg/mL, P < 0.001). In the multivariable regression analysis, only the type of operation and postoperative eCrCl were significantly correlated with PTH at follow-up. A limited parathyroidectomy was associated with a fivefold increase in risk of persistent or recurrent hyperparathyroidism. CONCLUSIONS: The use of limited parathyroidectomy for tertiary HPT after kidney transplantation has a higher risk of persistent/recurrent HPT. Subtotal parathyroidectomy is recommended for patients with tertiary HPT.

    Title Risks for End-stage Renal Disease, Cardiovascular Events, and Death in Hispanic Versus Non-hispanic White Adults with Chronic Kidney Disease.
    Date January 2007
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Rates of ESRD are rising faster in Hispanic than non-Hispanic white individuals, but reasons for this are unclear. Whether rates of cardiovascular events and mortality differ among Hispanic and non-Hispanic white patients with chronic kidney disease (CKD) also is not well understood. Therefore, this study examined the associations between Hispanic ethnicity and risks for ESRD, cardiovascular events, and death in patients with CKD. A total of 39,550 patients with stages 3 to 4 CKD from Kaiser Permanente of Northern California were included. Hispanic ethnicity was obtained from self-report supplemented by surname matching. GFR was estimated from the abbreviated Modification of Diet in Renal Disease equation, and clinical outcomes, patient characteristics, and longitudinal medication use were ascertained from health plan databases and state mortality files. After adjustment for sociodemographic characteristics, Hispanic ethnicity was associated with an increased risk for ESRD (hazard ratio [HR] 1.93; 95% confidence interval [CI] 1.72 to 2.17) when compared with non-Hispanic white patients, which was attenuated after controlling for diabetes and insulin use (HR 1.50; 95% CI 1.33 to 1.69). After further adjustment for potential confounders, Hispanic ethnicity remained independently associated with an increased risk for ESRD (HR 1.33; 95% CI 1.17 to 1.52) as well as a lower risk for cardiovascular events (HR 0.82; 95% CI 0.76 to 0.88) and death (HR 0.72; 95% CI 0.66 to 0.79). Among a large cohort of patients with CKD, Hispanic ethnicity was associated with lower rates of death and cardiovascular events and a higher rate of progression to ESRD. The higher prevalence of diabetes among Hispanic patients only partially explained the increased risk for ESRD. Further studies are required to elucidate the cause(s) of ethnic disparities in CKD-associated outcomes.

    Title Cystatin C and Measures of Physical Function in Elderly Adults: the Health, Aging, and Body Composition (habc) Study.
    Date January 2007
    Journal American Journal of Epidemiology
    Excerpt

    Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function.

    Title Validity of International Classification of Diseases, Ninth Revision, Clinical Modification Codes for Acute Renal Failure.
    Date January 2007
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Administrative and claims databases may be useful for the study of acute renal failure (ARF) and ARF that requires dialysis (ARF-D), but the validity of the corresponding diagnosis and procedure codes is unknown. The performance characteristics of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for ARF were assessed against serum creatinine-based definitions of ARF in 97,705 adult discharges from three Boston hospitals in 2004. For ARF-D, ICD-9-CM codes were compared with review of medical records in 150 patients with ARF-D and 150 control patients. As compared with a diagnostic standard of a 100% change in serum creatinine, ICD-9-CM codes for ARF had a sensitivity of 35.4%, specificity of 97.7%, positive predictive value of 47.9%, and negative predictive value of 96.1%. As compared with review of medical records, ICD-9-CM codes for ARF-D had positive predictive value of 94.0% and negative predictive value of 90.0%. It is concluded that administrative databases may be a powerful tool for the study of ARF, although the low sensitivity of ARF codes is an important caveat. The excellent performance characteristics of ICD-9-CM codes for ARF-D suggest that administrative data sets may be particularly well suited for research endeavors that involve patients with ARF-D.

    Title The Enlarging Body of Evidence: Obesity and Chronic Kidney Disease.
    Date January 2007
    Journal Journal of the American Society of Nephrology : Jasn
    Title A Simulation Model to Estimate the Cost and Effectiveness of Alternative Dialysis Initiation Strategies.
    Date December 2006
    Journal Medical Decision Making : an International Journal of the Society for Medical Decision Making
    Excerpt

    BACKGROUND: Patients with end-stage renal disease (ESRD) require dialysis to maintain survival. The optimal timing of dialysis initiation in terms of cost-effectiveness has not been established. METHODS: We developed a simulation model of individuals progressing towards ESRD and requiring dialysis. It can be used to analyze dialysis strategies and scenarios. It was embedded in an optimization frame worked to derive improved strategies. RESULTS: Actual (historical) and simulated survival curves and hospitalization rates were virtually indistinguishable. The model overestimated transplantation costs (10%) but it was related to confounding by Medicare coverage. To assess the model's robustness, we examined several dialysis strategies while input parameters were perturbed. Under all 38 scenarios, relative rankings remained unchanged. An improved policy for a hypothetical patient was derived using an optimization algorithm. CONCLUSION: The model produces reliable results and is robust. It enables the cost-effectiveness analysis of dialysis strategies.

    Title The Metabolic Syndrome and Chronic Kidney Disease.
    Date November 2006
    Journal Current Opinion in Nephrology and Hypertension
    Excerpt

    PURPOSE OF REVIEW: The metabolic syndrome is a constellation of physical and laboratory abnormalities including hypertension, hyperglycemia, hyperlipidemia and abdominal obesity. Over the past decade, the metabolic syndrome has emerged as a critically important risk factor for cardiovascular disease. RECENT FINDINGS: A large population-based cross-sectional analysis (the National Health and Nutrition Evaluation Survey III) found that the presence of the metabolic syndrome was associated with chronic kidney disease, defined as an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m and was also associated with proteinuria. More recently, a prospective cohort study found that the presence of the metabolic syndrome was associated with incident chronic kidney disease by the same definition, even when excluding individuals with diabetes mellitus and hypertension. More studies are required to determine whether the relationship between the metabolic syndrome and chronic kidney disease is mainly mediated by hyperglycemia (with insulin resistance) and hypertension, or other metabolic or hemodynamic factors. SUMMARY: The metabolic syndrome is associated with chronic kidney disease. Efforts aimed at determining the mechanisms underlying this association and strategies for the prevention of chronic kidney disease (or slowing the progression of chronic kidney disease) in affected patients should be research priorities in the future.

    Title Cystatin C, Left Ventricular Hypertrophy, and Diastolic Dysfunction: Data from the Heart and Soul Study.
    Date November 2006
    Journal Journal of Cardiac Failure
    Excerpt

    BACKGROUND: Impaired kidney function, as measured by serum cystatin C, is associated with risk of incident heart failure. Whether cystatin C is associated with preclinical cardiac structural abnormalities is unknown. We evaluate whether cystatin C is associated with left ventricular hypertrophy, diastolic dysfunction, and systolic dysfunction among 818 outpatients with coronary artery disease who were free of clinical heart failure. METHODS AND RESULTS: The 818 study participants were categorized into quartiles based on serum cystatin C concentrations, with < or =0.91 mg/L constituting the lowest quartile (I) and > or =1.28 mg/L constituting the highest (IV). Left ventricular hypertrophy (left ventricular mass index >90 g/m(2) by truncated ellipsoid method), diastolic dysfunction (impaired relaxation, pseudo-normal, or restrictive filling patterns) and systolic dysfunction (left ventricular ejection fraction < or =50%) were determined by echocardiography. Left ventricular hypertrophy was present in 68% of participants in quartile IV, compared with 44% of those in quartile I (adjusted odds ratio [OR] 2.17; 95% confidence interval [CI] 1.34 to 3.52; P = .002). Diastolic dysfunction was present in 52% of participants in quartile IV, compared with 24% of those in quartile I (adjusted OR 1.79; 95% CI 1.04 to 3.11; P = .04). Systolic dysfunction was present in 12% of those in quartile IV, compared with 6% of those in quartile I (adjusted OR 1.83; 95% CI 0.75 to 4.46; P = .15). CONCLUSION: Higher cystatin C concentrations are strongly associated with left ventricular hypertrophy and diastolic dysfunction in outpatients with coronary artery disease and without heart failure.

    Title Mortality After Acute Renal Failure: Models for Prognostic Stratification and Risk Adjustment.
    Date October 2006
    Journal Kidney International
    Excerpt

    To adjust adequately for comorbidity and severity of illness in quality improvement efforts and prospective clinical trials, predictors of death after acute renal failure (ARF) must be accurately identified. Most epidemiological studies of ARF in the critically ill have been based at single centers, or have examined exposures at single time points using discrete outcomes (e.g., in-hospital mortality). We analyzed data from the Program to Improve Care in Acute Renal Disease (PICARD), a multi-center observational study of ARF. We determined correlates of mortality in 618 patients with ARF in intensive care units using three distinct analytic approaches. The predictive power of models using information obtained on the day of ARF diagnosis was extremely low. At the time of consultation, advanced age, oliguria, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality. Upon initiation of dialysis for ARF, advanced age, hepatic failure, respiratory failure, sepsis, and thrombocytopenia were associated with mortality; higher blood urea nitrogen and lower serum creatinine were also associated with mortality in logistic regression models. Models incorporating time-varying covariates enhanced predictive power by reducing misclassification and incorporating day-to-day changes in extra-renal organ system failure and the provision of dialysis during the course of ARF. Using data from the PICARD multi-center cohort study of ARF in critically ill patients, we developed several predictive models for prognostic stratification and risk-adjustment. By incorporating exposures over time, the discriminatory power of predictive models in ARF can be significantly improved.

    Title Tesio Catheter Access for Long-term Maintenance Hemodialysis.
    Date October 2006
    Journal Radiology
    Excerpt

    PURPOSE: To retrospectively determine the long-term outcome (>6 months) of placement of tunneled hemodialysis catheters. MATERIALS AND METHODS: The HIPAA-compliant study protocol was approved by the Committee on Human Research, which waived the requirement for informed consent. The records of patients who underwent hemodialysis with the Tesio system (Medcomp, Harleysville, Pa) at a single outpatient dialysis unit between March 1994 and March 2004 were reviewed. The length of catheter access and the requirements for percutaneous revision were recorded, and unassisted- and assisted-access survival times were computed by using the Kaplan-Meier method. RESULTS: Three hundred three primary Tesio accesses were created in 200 patients (mean age, 62.3 years +/- 16.3 [standard deviation]; 102 women [51.0%]). Fifty-nine of 303 accesses (19.5%) were percutaneously revised with catheter exchange. During follow-up, 200 of 303 accesses (66.0%) were terminated (117 because they were no longer needed and 83 because of catheter malfunction), and 103 (34.0%) accesses were functioning at the time of last follow-up. The mean duration of catheter access was 247 days (range, 3-2016 days). One hundred twenty-six (41.6%) accesses remained in use for more than 6 months; 50 (16.5%), for more than 1 year; 20 (6.6%), for more than 2 years; 14 (4.6%), for more than 3 years; and five (1.7%), for more than 4 years. Assisted-access survival was 78.1%, 60.0%, 51.5%, 51.5%, and 46.8% at 6 months and 1, 2, 3, and 4 years, respectively. CONCLUSION: Tesio catheters frequently function for periods longer than 6 months and, when necessary, they can function for many years.

    Title Correlates and Outcomes of Dementia Among Dialysis Patients: the Dialysis Outcomes and Practice Patterns Study.
    Date October 2006
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Recent studies suggest a high prevalence of cognitive impairment and dementia in persons with end-stage renal disease (ESRD), yet risk factors for dementia and its prognostic significance in persons with ESRD remain unclear. The goals of this study were to determine the prevalence, correlates and dialysis-related outcomes of dementia in an international sample of haemodialysis patients. METHODS: We analysed data collected from a cohort of 16 694 patients in the Dialysis Outcomes and Practice Patterns Study. Dementia was defined as a diagnosis of dementia documented in the medical record. We used logistic regression to determine the baseline correlates of dementia and Cox proportional hazards models to determine the relative risk (RR) of death and dialysis withdrawal for patients with dementia, while adjusting for a number of confounding factors. RESULTS: Overall, 4% of the cohort had a recorded diagnosis of dementia. In the cross-sectional analyses, risk factors for dementia in the general population including age, black race, low educational attainment, cerebrovascular disease and diabetes, as well as modifiable uraemia-related factors, including markers of malnutrition and anaemia, were independently associated with dementia. After adjustment for a number of confounding factors, dementia was associated with an increased risk of death [RR 1.48, 95% confidence interval (CI) 1.32-1.66] and dialysis withdrawal (RR 2.01, 95% CI 1.57-2.57). CONCLUSIONS: Dementia is associated with adverse outcomes among ESRD patients. Dialysis providers should consider instituting routine screening for cognitive impairment among elderly patients in order to identify those at risk for associated adverse outcomes.

    Title Declining Mortality in Patients with Acute Renal Failure, 1988 to 2002.
    Date September 2006
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Despite improvements in intensive care and dialysis, some experts have concluded that outcomes associated with acute renal failure (ARF) have not improved significantly over time. ARF was studied in hospitalized patients between 1988 and 2002 using the Nationwide Inpatient Sample, a nationally representative sample of discharges from acute-care, nonfederal hospitals. During a 15-yr period, 5,563,381 discharges with ARF and 598,768 with ARF that required dialysis (ARF-D) were identified. Between 1988 and 2002, the incidence of ARF rose from 61 to 288 per 100,000 population; the incidence of ARF-D increased from 4 to 27 per 100,000 population. Between 1988 and 2002, in-hospital mortality declined steadily in patients with ARF (40.4 to 20.3%; P < 0.001) and in those with ARF-D (41.3 to 28.1%; P < 0.001). Compared with 1988 to 1992, the multivariable-adjusted odds ratio (OR) of death was lower in 1993 to 1997 (ARF: OR 0.62, 95% confidence interval [CI] 0.61 to 0.64; ARF-D: OR 0.63, 95% CI 0.59 to 0.66) and 1998 to 2002 (ARF: OR 0.40, 95% CI 0.39 to 0.41; ARF-D: OR 0.47, 95% CI 0.45 to 0.50). The percentage of patients who had ARF with a Deyo-Charlson comorbidity index of 3 or more increased from 16.4% in 1988 to 26.6% in 2002 (P < 0.001). This study provides evidence from an administrative database that the incidence of ARF and ARF-D is rising. Despite an increase in the degree of comorbidity, in-hospital mortality has declined.

    Title Guidelines for Disorders of Mineral Metabolism and Secondary Hyperparathyroidism Should Not Yet Be Modified.
    Date September 2006
    Journal Nature Clinical Practice. Nephrology
    Excerpt

    This brief article is a response to the article by Monge et al. on page 326 entitled Reappraisal of 2003 NKF-K/DOQI guidelines for management of hyperparathyroidism in chronic kidney disease patients. We contend that there is insufficient evidence to support the changes to clinical practice and clinical practice guidelines proposed by Monge and colleagues. We recommend that clinical trials be conducted to resolve these points of contention and other critical issues in the management of disorders of mineral metabolism in chronic kidney disease, including secondary hyperparathyroidism. The focus should be on evaluating the effects of alternative strategies on survival, as well as clinical manifestations of cardiovascular and bone disease.

    Title Self-assessed Sleep Quality in Chronic Kidney Disease.
    Date September 2006
    Journal International Urology and Nephrology
    Excerpt

    BACKGROUND: Although sleep complaints are commonly reported in persons with end stage renal disease (ESRD), little is known about the prevalence of sleep complaints in chronic kidney disease (CKD), and the relation of sleep quality to the severity of kidney disease. METHODS: We administered the Kidney Disease Quality of Life (KDQOL) sleep scale to 156 subjects, 78 with ESRD and 78 with CKD. Glomerular filtration rate (GFR) was estimated using the six variable Modification of Diet in Renal Disease (MDRD) equation and used to stratify subjects with CKD as mild-moderate (GFR >25 ml/min/1.73 m(2)) and advanced (GFR <25 ml/min/1.73 m(2)). We used multivariable linear regression to determine independent predictors of KDQOL sleep scale scores. Higher scores indicate higher self-reported quality of sleep. RESULTS: Median scores on the KDQOL sleep scale were 59 (interquartile range 40-80) in subjects with ESRD and 69 (interquartile range 53-80) in subjects with CKD (P=0.04). Thirty-four percent of subjects with ESRD, 27% of subjects with advanced CKD, and 14% of subjects with mild to moderate CKD had sleep maintenance disturbances (P=0.05). Thirteen percent of subjects with ESRD, 11% of subjects with advanced CKD, and no subjects with mild-moderate CKD had complaints of daytime somnolence (P=0.03). There was no significant difference in the prevalence of sleep adequacy complaints in persons with ESRD versus CKD. In multivariable analyses, only age and ESRD status (vs. CKD) were significant predictors of lower KDQOL sleep scores. Among subjects with CKD, there was a significant direct association between estimated GFR and scores on the KDQOL sleep scale in non-African American subjects (P=0.01). CONCLUSIONS: Sleep complaints are common in persons with CKD and ESRD and may be associated with the severity of kidney disease.

    Title Lessons for Medicare Part D in the Hemodialysis Community.
    Date September 2006
    Journal Bmc Nephrology
    Excerpt

    BACKGROUND: Medicare beneficiaries without prescription drug coverage consistently fill fewer prescriptions than beneficiaries with some form of drug coverage due to cost. ESRD patients, who are disproportionately poor and typically use multiple oral medications, would likely benefit substantially from any form of prescription drug coverage. Because most hemodialysis patients are Medicare-eligible, they as well as their providers would be expected to be well informed of changes in Medicare prescription drug coverage. By examining the level of understanding and use of the temporary Medicare Prescription Drug Discount Card Program in the hemodialysis population, we can gain a better understanding of the potential long-term utilization for Medicare Part D. METHODS: We surveyed English-speaking adult hemodialysis patients with Medicare coverage from two urban hemodialysis centers affiliated with the University of California San Francisco (UCSF) during July and August 2005 (n = 70). We also surveyed University- and community-based nephrologists and non-physician dialysis health care professionals over the same time frame (n = 70). RESULTS: Fifty-nine percent of patients received prescription drug coverage through Medi-Cal, 20% through another insurance program, and 21% had no prescription drug coverage. Forty percent of patients with no prescription drug coverage reported "sometimes" or "rarely" being able to obtain medications vs. 22% of patients with some form of drug coverage. None of the patients surveyed actually had a Medicare-approved prescription drug card, and of those who intended to apply, only 10% reported knowing how to do so. Only 11% health care professionals knew the eligibility requirements of the drug discount cards. CONCLUSION: Despite a significant need, hemodialysis patients and providers were poorly educated about the Medicare Prescription Drug Discount Cards. This has broad implications for the dissemination of information about Medicare Part D.

    Title Renal Function and Heart Failure Risk in Older Black and White Individuals: the Health, Aging, and Body Composition Study.
    Date August 2006
    Journal Archives of Internal Medicine
    Excerpt

    BACKGROUND: Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites. METHODS: The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure. RESULTS: Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence). CONCLUSION: The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.

    Title The Tortoise and Hare on Hemodialysis: Does Slow and Steady Win the Race?
    Date August 2006
    Journal Kidney International
    Excerpt

    The importance of hemodialysis session length relative to small solute (e.g., urea) clearance has been debated for many years. Longer session length augments clearance of larger molecules and may facilitate ultrafiltration; however, the independent effects of session length on survival and other outcomes are unknown. In this report, we review two recently published observational studies examining the association between hemodialysis session length and survival. Prospective clinical trials will be required to resolve the debate.

    Title Update on Adverse Drug Events Associated with Parenteral Iron.
    Date July 2006
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex. METHODS: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars. CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.

    Title Chronic Kidney Disease and Functional Limitation in Older People: Health, Aging and Body Composition Study.
    Date June 2006
    Journal Journal of the American Geriatrics Society
    Excerpt

    OBJECTIVES: To assess whether chronic kidney disease (CKD) is independently associated with incident physical-function limitation. DESIGN: Prospective cohort study. SETTING: Two sites: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand one hundred thirty-five men and women aged 70 to 79 without functional limitation at baseline from the Health, Aging and Body Composition Study. MEASUREMENTS: Functional limitation was defined as difficulty in walking one-quarter of a mile or climbing 10 steps on two consecutive reports 6 months apart (in the same function). Kidney function was measured using serum cystatin C. Estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula (<60 versus > or =60 mL/min per 1.73 m(2)), was a secondary predictor. Muscle strength, lean body mass according to dual energy x-ray absorptiometry, comorbidity, medication use, and inflammatory markers were evaluated as covariates. RESULTS: Persons in the highest (> or =1.13 mg/L) quartile of cystatin C experienced a significantly higher risk of developing functional limitation than those in the lowest (<0.86 mg/L) quartile (hazard ratio (HR)=1.70, 95% confidence interval (CI)=1.40-2.07). The association between the fourth cystatin C quartile and functional limitation remained after adjustment for demographics, lean body mass, comorbidity, muscle strength, and gait speed (HR=1.41, 95% CI=1.13-1.75), although the association was attenuated after adjustment for markers of inflammation (HR=1.15, 95% CI=0.90-1.46). Similar results were found for eGFR less than 60 mL/min per 1.73 m(2), although the association with functional limitation remained after adjustment for inflammatory markers (HR=1.30, 95% CI=1.08-1.56). CONCLUSION: CKD is associated with the development of functional impairment independent of comorbidity, body composition, and tests of strength and physical performance. The mechanism may be related to a heightened inflammatory state in CKD.

    Title Cystatin C and Mortality Risk in the Elderly: the Health, Aging, and Body Composition Study.
    Date June 2006
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-alpha), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, -1.0 (referent); quintile 2, -1.74 (1.21 to 2.50); quintile 3, -1.51 (1.05 to 2.18); quintile 4, -1.49 (1.04 to 2.13); and quintile 5, -2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.

    Title Bone Disease and Bottle Caps.
    Date May 2006
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Title Differential Mortality and Transplantation Rates Among Asians and Pacific Islanders with Esrd.
    Date April 2006
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Few studies in patients with ESRD have examined outcomes in Asian or Pacific Islander subgroups compared with white individuals. The objective of this study was to assess ethnic disparities in mortality and kidney transplantation among a multiethnic cohort of incident dialysis patients. A total of 24,963 patients who initiated dialysis within the TransPacific Renal Network (Network 17) between April 1, 1995, and September 30, 2001, were studied to ascertain death and kidney transplantation through September 30, 2002. Overall, 12,902 deaths and 2258 kidney transplantations were observed during 59,075 person-years of follow-up. Mortality on dialysis among Asians and Pacific Islanders (except Chamorros) was lower than that of white individuals after controlling for differences in sociodemographic characteristics, comorbid conditions, and other risk factors for death (adjusted hazard ratio [95% confidence interval] versus white individuals: Japanese 0.64 [0.57 to 0.72], Chinese 0.64 [0.52 to 0.78], Filipino 0.64 [0.57 to 0.72], Native Hawaiian 0.84 [0.72 to 0.96], Samoan 0.62 [0.48 to 0.82], and Chamorro 0.96 [0.84 to 1.20]). In contrast, Asians and Pacific Islanders were much less likely to undergo kidney transplantation (adjusted rate ratio [95% confidence interval] versus white individuals: Japanese 0.34 [0.24 to 0.46], Chinese 0.54 [0.30 to 0.88], Filipino 0.32 [0.26 to 0.47], Native Hawaiian 0.17 [0.10 to 0.30], Samoan 0.17 [0.07 to 0.38], and Chamorro 0.04 [0.01 to 0.14]). Despite wide variations in primary cause of ESRD, clinical characteristics, and body size at dialysis initiation, Asians and Pacific Islanders experience better survival but substantially lower transplantation rates compared with white individuals. Strategies that are aimed at improving access to transplantation in Asian and Pacific Islander communities may further enhance survival among Asians and Pacific Islanders with ESRD.

    Title Association of Body Size with Health Status in Patients Beginning Dialysis.
    Date April 2006
    Journal The American Journal of Clinical Nutrition
    Excerpt

    BACKGROUND: Greater weight-for-height has been associated with prolonged survival in patients with end-stage renal disease (ESRD) but not in the general population. The association between body size and health status has not been carefully evaluated. OBJECTIVES: We compared the self-reported health status of 2467 participants in the Dialysis Morbidity and Mortality Study Wave 2 by using body mass index (BMI; in kg/m2) to approximate body size and composition. DESIGN: BMI was categorized into 4 groups (<19, 19 to <25, 25 to <30, and > or = 30) corresponding to World Health Organization criteria for underweight, normal-weight, overweight, and obese status. We adjusted for demographic, clinical, and laboratory factors that may have confounded the association between body size and health status. RESULTS: Scores on the physical component summary and the physical functioning scale were significantly lower for obese subjects than for those with normal weight or moderately high BMI after adjustment for demographic factors, comorbidity, and laboratory markers of nutritional status. Mental component summary and symptom scores were unrelated to BMI. The underweight group scored lower on many Medical Outcomes Study 36-Item Short Form scales than did the normal-weight group. CONCLUSIONS: Whereas higher BMI has consistently been associated with enhanced dialysis-related survival, health status-particularly physical function-may be impaired by obesity. Additional longitudinal studies of body weight and composition are needed for a better understanding of the complex effects of obesity and undernutrition in persons with ESRD and advanced chronic kidney disease.

    Title Acute Renal Failure After Endovascular Vs Open Repair of Abdominal Aortic Aneurysm.
    Date April 2006
    Journal Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter
    Excerpt

    OBJECTIVE: Endovascular aneurysm repair (EVAR) is an increasingly used alternative to open surgical repair of unruptured abdominal aortic aneurysms (AAAs). The effect of EVAR on postprocedure acute renal failure has not been determined. We hypothesized that EVAR would be associated with a lower risk of acute renal failure and acute renal failure requiring hemodialysis. METHODS: A retrospective cohort study was conducted of the 2002 Nationwide Inpatient Sample, the largest all-payer inpatient care database in the United States, reflecting discharges from a representative sample of United States hospitals. We identified 6614 discharges with a primary diagnosis of unruptured AAA and a primary procedure code for open AAA repair or EVAR. We excluded 56 patients with end-stage renal disease and 42 patients who underwent concomitant aortorenal bypass. We compared EVAR vs open repair in this cohort. The main outcome measures were acute renal failure and acute renal failure requiring dialysis. RESULTS: A total of 6516 patient discharges met the inclusion criteria for the study, and postprocedure acute renal failure developed in 439 (6.7%). EVAR was associated with lower odds of acute renal failure (adjusted odds ratio, 0.42; 95% confidence interval, 0.33 to 0.53) and acute renal failure requiring dialysis (adjusted odds ratio, 0.30, 95% confidence interval, 0.15 to 0.63). Results were similar when EVAR and open AAA repair were compared within quintiles of the propensity score for the receipt of EVAR. CONCLUSIONS: Compared with open AAA repair, EVAR is associated with a lower risk of postprocedure acute renal failure.

    Title Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients.
    Date March 2006
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    The marginal effects of acute kidney injury on in-hospital mortality, length of stay (LOS), and costs have not been well described. A consecutive sample of 19,982 adults who were admitted to an urban academic medical center, including 9210 who had two or more serum creatinine (SCr) determinations, was evaluated. The presence and degree of acute kidney injury were assessed using absolute and relative increases from baseline to peak SCr concentration during hospitalization. Large increases in SCr concentration were relatively rare (e.g., >or=2.0 mg/dl in 105 [1%] patients), whereas more modest increases in SCr were common (e.g., >or=0.5 mg/dl in 1237 [13%] patients). Modest changes in SCr were significantly associated with mortality, LOS, and costs, even after adjustment for age, gender, admission International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis, severity of illness (diagnosis-related group weight), and chronic kidney disease. For example, an increase in SCr >or=0.5 mg/dl was associated with a 6.5-fold (95% confidence interval 5.0 to 8.5) increase in the odds of death, a 3.5-d increase in LOS, and nearly 7500 dollars in excess hospital costs. Acute kidney injury is associated with significantly increased mortality, LOS, and costs across a broad spectrum of conditions. Moreover, outcomes are related directly to the severity of acute kidney injury, whether characterized by nominal or percentage changes in serum creatinine.

    Title Self-reported Appetite, Hospitalization and Death in Haemodialysis Patients: Findings from the Hemodialysis (hemo) Study.
    Date February 2006
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Anorexia is an important cause of protein-energy malnutrition (PEM) in haemodialysis patients. We investigated whether self-reported appetite was associated with death and hospitalization in subjects enrolled in the Hemodialysis (HEMO) Study. METHODS: The HEMO Study was a 7-year, multicentre, randomized trial (N = 1846), which examined the effects of dialysis dose and membrane flux on mortality and morbidity. Three questions from the Appetite and Diet Assessment Tool (ADAT) were used to determine whether appetite had changed over time in the randomized treatment groups. The relations among ADAT scores, dietary protein and energy intakes, biochemical and anthropometric measures, and quality of life were assessed. We used Cox proportional hazards models to evaluate the relative risks of death and hospitalization associated with static and dynamic ADAT scores, adjusted for demographic factors, dose and flux assignments, and co-morbidity. RESULTS: The average length of follow-up was 2.84 years. After adjusting for demographic factors and randomized treatment assignments, there was a significant association between poorer self-reported appetite and death (RR 1.52, 95% CI 1.16-1.98); however, the association became non-significant with further adjustment for co-morbidity (RR 1.23, 95% CI 0.94-1.62). Poorer appetite was unequivocally associated with increased hospitalization rates (multivariable RR 1.35, 95% CI 1.13-1.61). The longitudinal effect of worsening appetite from baseline to 1 year was not associated with mortality or hospitalization rate after adjusting for co-morbidity. CONCLUSIONS: The association between appetite and death was confounded by co-morbidity. Self-reported appetite was associated with hospitalization rate in haemodialysis patients and, thus, it may be a useful screening tool for this outcome. Patients who report poor or very poor appetites should be monitored, and they should receive more comprehensive nutritional assessments.

    Title Pth and the Risks for Hip, Vertebral, and Pelvic Fractures Among Patients on Dialysis.
    Date February 2006
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    BACKGROUND: Few investigations have described fracture risk and its relation to disorders in calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) metabolism in the end-stage renal disease population. METHODS: Laboratory values for Ca, P, and PTH were obtained from Dialysis Morbidity and Mortality Study (DMMS) Waves 1 to 4. Additional data available from the US Renal Data System were used to determine the incidence and associated costs of hip, vertebral, and pelvic fractures in 9,007 patients with nonmissing laboratory values and Medicare as primary payor. Cox proportional hazards and Poisson models were used to analyze time to first fracture and numbers of fractures, respectively. RESULTS: There was no association between Ca or P values and risk for fracture; risks for vertebral and hip fractures and PTH concentrations were U shaped and weakly significant using Poisson regression (P = 0.03). The age- and sex-adjusted mortality rate after fracture was 2.7 times greater (580/1,000 person-years) than for general dialysis patients from the DMMS (217/1,000 person-years). Mean total episodic costs of hip, vertebral, and pelvic fractures were 20,810 dollars +/- 16,743 dollars (SD), 17,063 dollars +/- 26,201 dollars, and 14,475 dollars +/- 19,209 dollars, respectively. CONCLUSION: Using data from the DMMS, there were no associations between Ca and P concentrations and risk for fracture. Risks for hip and vertebral fracture were associated weakly with PTH concentration, with the lowest risk observed around a PTH concentration of 300 pg/mL (ng/L). Fractures were associated with high subsequent mortality and costs. Prospective studies are needed to determine whether therapies that maintain PTH concentrations within or near the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative range will result in fewer complications of disordered mineral metabolism.

    Title Challenging the Validity of the Epo Index.
    Date February 2006
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    BACKGROUND: With use of recombinant erythropoietin (EPO) and intravenous iron, the majority of hemodialysis patients can achieve target hemoglobin concentrations. EPO resistance arises as a consequence of inflammation and other processes that can adversely affect survival. We hypothesized that the EPO dose-hematocrit (EPO/Hct) ratio, also known as the EPO index, may be a surrogate for inflammation and that greater EPO/Hct ratios would be associated with decreased survival. METHODS: We used proportional hazards regression models and time-varying logistic models to analyze the association between EPO index and survival in US hemodialysis patients initiating hemodialysis therapy between January 1, 1999, and December 31, 2000, and followed up for up to 3 years until December 31, 2001. RESULTS: We found an unexpected and consistent association between greater EPO index and survival in all models. The associations of EPO/Hct ratio were most prominent at intermediate Hct values and with longer dialysis vintage. Iron administration was associated with a lower risk for death independent of Hct. Conversely, greater average prior EPO dose was associated with a greater risk for death. CONCLUSION: EPO resistance may be reflected better by total cumulative EPO dose than the EPO/Hct ratio. The mechanism(s) responsible for the association between a greater EPO/Hct ratio and survival remains to be established, but may be a result of nonerythrogenic effects of EPO.

    Title Prealbumin, Mortality, and Cause-specific Hospitalization in Hemodialysis Patients.
    Date January 2006
    Journal Kidney International
    Excerpt

    BACKGROUND: Prealbumin (transthyretin) is a hepatic secretory protein thought to be important in the evaluation of nutritional deficiency and nutrition support. Prior studies have suggested that the serum prealbumin concentration is independently associated with mortality in hemodialysis patients, even with adjustment for serum albumin and other nutritional parameters. METHODS: To determine whether prealbumin was independently associated with mortality and morbidity (cause-specific hospitalization) in hemodialysis patients, we analyzed data on 7815 hemodialysis patients with at least one determination of serum prealbumin during the last three months of 1997. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum prealbumin using proportional hazards regression. We also determined whether the prealbumin concentration was associated with all-cause, cardiovascular, infection-related, and vascular access-related hospitalization. RESULTS: The relative risk (RR) of death was inversely related to the serum prealbumin concentration. Relative to prealbumin > or =40 mg/dL, the adjusted RRs of death were 2.41, 1.85, 1.49, and 1.23 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. The adjusted RRs of hospitalization due to infection were 2.97, 1.95, 1.81, and 1.61 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. The adjusted RRs of vascular access-related hospitalization were 0.48, 0.52, 0.58, and 0.71 for prealbumin <15, 15-20, 20-25, and 25-30 mg/dL, respectively. While serum albumin was strongly associated with mortality and all-cause hospitalization, it was not associated with hospitalization due to infection, and lower levels were associated with higher rather than lower rates of vascular access-related hospitalization. CONCLUSION: In hemodialysis patients, lower prealbumin concentrations were associated with mortality and hospitalization due to infection, independent of serum albumin and other clinical characteristics. Higher prealbumin concentrations were associated with vascular access-related hospitalization. In light of these findings, more intensive study into the determinants and biological actions of prealbumin (transthyretin) in end-stage renal disease is warranted.

    Title Health-related Quality of Life and Estimates of Utility in Chronic Kidney Disease.
    Date January 2006
    Journal Kidney International
    Excerpt

    BACKGROUND: Health-related quality of life and estimates of utility have been carefully evaluated in persons with end-stage renal disease. Fewer studies have examined these parameters in persons with chronic kidney disease (CKD). METHODS: To determine the relations among kidney function, health-related quality of life, and estimates of utility, we administered the Kidney Disease Quality of Life Short Form 36 (KDQOL-36), Health Utilities Index (HUI)-3, and Time Trade-off (TTO) questionnaires to 205 persons with CKD. Persons with CKD stages 4 and 5 (estimated GFR <30 mL/min/1.73 m2, N= 115) were tested two to eight times over the subsequent two years. The relations among estimated glomerular filtration rate (eGFR), and changes in health-related quality of life and utility over time were estimated using mixed effect regression models. Models were adjusted for age, sex, race, and diabetes. RESULTS: Mean scores on the KDQOL-36 generic components, HUI-3, and TTO suggested considerable loss of function and well-being in CKD relative to population norms. On cross-sectional analysis, lower levels of kidney function were associated with significantly lower scores on the SF-12 Physical Health Composite (P= 0.002), the Burden of Kidney Disease subscale (P < 0.0001), and the Effects of Kidney Disease subscale (P < 0.0001) of the KDQOL-36trade mark. Kidney function was significantly associated with the TTO (P= 0.008) and global HUI-3 utility (P= 0.016) although these associations were attenuated after adjustment for diabetes. A decline in eGFR was associated with a significant increase in the reported Burden of Kidney Disease (5.0 point change per year per mL/min/1.73 m2 decline in eGFR) and with marginally significant changes in the Dexterity and Pain attributes of the HUI-3. Mean HUI-3 scores for persons with CKD stages 4 and 5, absent dialysis, were in the range previously reported for persons with stroke and severe peripheral vascular disease. CONCLUSION: Health-related quality of life and estimates of utility are distressingly low in persons with CKD. Self-reported outcomes should be considered when evaluating health policy decisions that affect this population.

    Title Are Nutritional Status Indicators Associated with Mortality in the Hemodialysis (hemo) Study?
    Date December 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: The purpose of this study was to determine if indicators of nutritional status were associated with subsequent mortality in hemodialysis patients. METHODS: Twelve selected nutrition indicators were measured prior to randomization in the Mortality and Morbidity in Hemodialysis (HEMO) Study. Relative risks (RR) of mortality were assessed at <6 months and >6 months of follow-up using Cox regression after controlling for case mix, comorbidity, and treatment assignment (high vs. standard Kt/V and high vs. low membrane flux). RESULTS: Low values of most nutritional status indicators were associated with increased RR of mortality. RRs were greatest over the short term (<6 months) and diminished with increasing follow-up (>6 months). Increases in body mass index (BMI) at lower levels (e.g., < or =25 kg/m(2)) and increases in serum albumin at any level were associated with reduced short-term RR, even after adjusting for case mix, treatment assignment, and for the joint effects of equilibrated normalized protein catabolic rate, total cholesterol, and serum creatinine. For >6 months' follow-up, increases in values among those with lower levels of BMI and serum albumin (< or =3.635 g/dL) and increases in all serum creatinine levels were associated with lower RR. CONCLUSION: Nutrition indicators are associated with subsequent mortality in a time-dependent manner, with greatest effects at <6 months of follow-up. The RR for these indicators may also vary within different ranges of values.

    Title Effects of the Calcimimetic Cinacalcet Hcl on Cardiovascular Disease, Fracture, and Health-related Quality of Life in Secondary Hyperparathyroidism.
    Date December 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: Secondary hyperparathyroidism (HPT) and abnormal mineral metabolism are thought to play an important role in bone and cardiovascular disease in patients with chronic kidney disease. Cinacalcet, a calcimimetic that modulates the calcium-sensing receptor, reduces parathyroid hormone (PTH) secretion and lowers serum calcium and phosphorus concentrations in patients with end-stage renal disease (ESRD) and secondary HPT. METHODS: We undertook a combined analysis of safety data (parathyroidectomy, fracture, hospitalizations, and mortality) from 4 similarly designed randomized, double-blind, placebo-controlled clinical trials enrolling 1184 subjects (697 cinacalcet, 487 control) with ESRD and uncontrolled secondary HPT (intact PTH > or =300 pg/mL). Cinacalcet or placebo was administered to subjects receiving standard care for hyperphosphatemia and secondary HPT (phosphate binders and vitamin D). Relative risks (RR) and 95% CI were calculated using proportional hazards regression with follow-up times from 6 to 12 months. Health-related quality-of-life (HRQOL) data were obtained from the Medical Outcomes Study Short Form-36 (SF-36), and the Cognitive Functioning scale from the Kidney Disease Quality of Life instrument (KDQOL-CF). RESULTS: Randomization to cinacalcet resulted in significant reductions in the risk of parathyroidectomy (RR 0.07, 95% CI 0.01-0.55), fracture (RR 0.46, 95% CI 0.22-0.95), and cardiovascular hospitalization (RR 0.61, 95% CI 0.43-0.86) compared with placebo. Changes in HRQOL favored cinacalcet, with significant changes observed for the SF-36 Physical Component Summary score and the specific domains of Bodily Pain and General Health Perception. CONCLUSION: Combining results from 4 clinical trials, randomization to cinacalcet led to significant reductions in the risk of parathyroidectomy, fracture, and cardiovascular hospitalization, along with improvements in self-reported physical function and diminished pain. These data suggest that, in addition to its effects on PTH and mineral metabolism, cinacalcet had favorable effects on important clinical outcomes.

    Title Potential Antiatherogenic and Anti-inflammatory Properties of Sevelamer in Maintenance Hemodialysis Patients.
    Date December 2005
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Patients affected by end-stage renal disease (ESRD) demonstrate a very high cardiovascular risk mediated by traditional cardiovascular risk factors as well as abnormal mineral metabolism and a state of chronic inflammation. Sevelamer is a nonabsorbable non-calcium-based hydrogel with potential antiatherosclerotic properties. METHOD AND RESULTS: One hundred eight patients undergoing maintenance hemodialysis were randomized to sevelamer or calcium acetate as treatment for hyperphosphatemia. A coronary artery calcium score, as a measure of plaque burden, was calculated at baseline and 1 year, along with serial measurements of serum lipoproteins, beta2-microglobulin, and high-sensitivity C-reactive protein (hs-CRP). At 1 year, coronary artery calcium score progressed significantly from baseline in calcium acetate-treated subjects ( P < .001) but not in sevelamer-treated patients (P = NS). Total cholesterol (P < .0001), low-density lipoprotein cholesterol (P < .0001), apolipoprotein B (P < .0001), beta2-microglobulin (P = .018), and hs-CRP (P < .002) decreased, and high-density lipoprotein increased significantly (P = .036) from baseline in the sevelamer-treated subjects but not in subjects treated with calcium acetate despite the more frequent use of statins in the latter group (46% vs 22%, P < .05). The changes in total and low-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP were significantly different between treatment groups (all P < .01). CONCLUSIONS: Sevelamer leads to favorable changes in lipids and inflammatory markers with potentially useful antiatherogenic effects in hemodialysis patients.

    Title Angiotensin Receptor Blockade and Arterial Compliance in Chronic Kidney Disease: a Pilot Study.
    Date November 2005
    Journal American Journal of Nephrology
    Excerpt

    BACKGROUND: Almost 20 million people in the US have chronic kidney disease (CKD). Cardiovascular disease and arterial wall abnormalities are common in this population. Because angiotensin II may have adverse effects on the arterial wall, we hypothesized that an angiotensin receptor blocker (ARB) would improve arterial compliance as compared with placebo in subjects with CKD. METHODS: We performed a double-blinded, placebo-controlled pilot study in which 25 subjects with stages 2 or 3 CKD and proteinuria <1 g were randomized to either the ARB, eprosartan, or placebo and titrated to achieve a goal blood pressure (BP) <130/85 mm Hg. Arterial compliance was measured at baseline and at 8 weeks. RESULTS: Baseline characteristics were similar between the groups and included mean estimated glomerular filtration rate 63 +/- 14 ml/min/1.73 m(2), heart rate 76 +/- 10 beats/min, BP 142 +/- 12/81 +/- 8 mm Hg, 64% diabetic, 44% male, and 40% white, though subjects in the eprosartan group were younger (60 +/- 12 vs. 70 +/- 6 years, p = 0.01). There were no significant differences between the groups in large or small artery compliance measurements either at baseline or at 8 weeks, but there was a statistically significant improvement from baseline in small artery compliance in the eprosartan group (from median 2.5 ml/mm Hg x 100 [90% CI (1.1, 4.7)] to 4.0 ml/mm Hg x 100 [90% CI (1.9, 6.7)] (p = 0.01)) not seen in the placebo group. CONCLUSION: Use of an ARB to achieve recommended BP is associated with improved small artery compliance in people with CKD, though larger studies are needed to confirm these findings.

    Title Control of Hypertension in Adults with Chronic Kidney Disease in the United States.
    Date November 2005
    Journal Hypertension
    Excerpt

    Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2 or presence of albuminuria (albumin:creatinine ratio >30 microg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.

    Title Chronic Kidney Disease and Cognitive Impairment in the Elderly: the Health, Aging, and Body Composition Study.
    Date November 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment. Whether the longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score <80 or a decline in 3MS >5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores > or =80. Participants with CKD, defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2, were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [CI] 1.03 to 1.69) and OR 2.43 (95% CI, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m2 and <45 ml/min per 1.73 m2, respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted.

    Title Metabolic Syndrome and the Risk for Chronic Kidney Disease Among Nondiabetic Adults.
    Date November 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    The metabolic syndrome is a risk factor for the development of diabetes and cardiovascular disease; however, no prospective studies have examined the metabolic syndrome as a risk factor for chronic kidney disease (CKD). A total of 10,096 nondiabetic participants who were in the Atherosclerosis Risk in Communities study and had normal baseline kidney function composed the study cohort. The metabolic syndrome was defined according to recent guidelines from the National Cholesterol Education Program. Incident CKD was defined as an estimated GFR (eGFR) <60 ml/min per 1.73 m2 at study year 9 among those with an eGFR > or =60 ml/min per 1.73 m2 at baseline. After 9 yr of follow-up, 691 (7%) participants developed CKD. The multivariable adjusted odds ratio (OR) of developing CKD in participants with the metabolic syndrome was 1.43 (95% confidence interval [CI], 1.18 to 1.73). Compared with participants with no traits of the metabolic syndrome, those with one, two, three, four, or five traits of the metabolic syndrome had OR of CKD of 1.13 (95% CI, 0.89 to 1.45), 1.53 (95% CI, 1.18 to 1.98), 1.75 (95% CI, 1.32 to 2.33), 1.84 (95% CI, 1.27 to 2.67), and 2.45 (95% CI, 1.32 to 4.54), respectively. After adjusting for the subsequent development of diabetes and hypertension during the 9 yr of follow-up, the OR of incident CKD among participants with the metabolic syndrome was 1.24 (95% CI, 1.01 to 1.51). The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults.

    Title Beyond Framingham: Cardiovascular Risk Profiling in Esrd.
    Date October 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Title Dialysis Session Length ("t") As a Determinant of the Adequacy of Dialysis.
    Date September 2005
    Journal Seminars in Nephrology
    Excerpt

    Several studies have shown an association between the hemodialysis session length (the t of Kt or Kt/V) and favorable outcomes for patients on maintenance hemodialysis. In a single randomized controlled trial that systematically varied hemodialysis session length, shorter session length was associated with an increased risk for morbidity and mortality, independent of the time-averaged concentration of urea. Observational studies of dialysis session length have yielded conflicting results, although virtually all studies have confounded hemodialysis session length with hemodialysis efficiency or dose. Limited observational data from nocturnal hemodialysis programs more strongly suggest an independent beneficial effect of longer session length. In aggregate, data on the effects of hemodialysis session length are inconclusive. Future studies should evaluate hemodialysis session length independent of efficiency, and should consider the evaluation of dose by using other clearance parameters and the adequacy of ultrafiltration in addition to solute kinetics.

    Title Chronic Kidney Disease and Cognitive Impairment in Menopausal Women.
    Date September 2005
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    BACKGROUND: Although end-stage renal disease has been associated with cognitive impairment, the relation between lesser degrees of chronic kidney disease (CKD) and cognitive impairment is less well understood. METHODS: Data for 1,015 women enrolled at 10 of the 20 Heart Estrogen/Progestin Replacement Study clinical sites were analyzed. All participants were younger than 80 years and had established coronary artery disease at study entry. Participants underwent 6 standard tests of cognitive function evaluating various domains. Unadjusted, residual age- and race-adjusted, and multivariable-adjusted linear and logistic regression models were used. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFRs, CKD was categorized as mild (estimated GFR [eGFR], 45 to 60 mL/min/1.73 m2), moderate (eGFR, 30 to 44 mL/min/1.73 m2), and severe (eGFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines. RESULTS: Mean eGFR was 57 +/- 14 mL/min/1.73 m2. In multivariable analyses, eGFR was associated significantly with impairment in global cognition, executive function, language, and memory (approximately 15% to 25% increase in risk for dysfunction/10-mL/min/1.73 m2 decrement in eGFR). Associations among eGFR and cognitive function were independent of residual effects of age and race (2 key determinants of GFR) and the contributions of education, lifestyle factors, stroke, diabetes, and other laboratory variables. CONCLUSION: CKD is associated with cognitive impairment in menopausal women with coronary artery disease.

    Title Medicare Esrd Prospective Payment System: Weighing the Evidence.
    Date August 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Title Decrease in Thoracic Vertebral Bone Attenuation with Calcium-based Phosphate Binders in Hemodialysis.
    Date August 2005
    Journal Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
    Excerpt

    We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. Subjects randomized to calcium salts experienced a significant reduction in trabecular bone attenuation and a trend toward reduction in cortical bone attenuation, in association with higher concentrations of serum calcium, lower concentrations of PTH, and reduced total and bone-specific alkaline phosphatase. INTRODUCTION: In patients with chronic kidney disease, hyperphosphatemia is associated with osteodystrophy, vascular and soft tissue calcification, and mortality. Calcium-based phosphate binders are commonly prescribed to reduce intestinal phosphate absorption and to attenuate secondary hyperparathyroidism. Clinicians and investigators have presumed that, in hemodialysis patients, calcium exerts beneficial effects on bone. MATERIALS AND METHODS: We performed a post hoc analysis of a 52-week randomized trial conducted in adult hemodialysis patients that compared the effects of calcium-based phosphate binders and sevelamer, a nonabsorbable polymer, on parameters of mineral metabolism and vascular calcification by electron beam tomography. In this analysis, we evaluated the relative effects of calcium and sevelamer on thoracic vertebral attenuation by CT and markers of bone turnover. RESULTS AND CONCLUSIONS: The average serum phosphorus and calcium x phosphorus products were similar for both groups, although the average serum calcium concentration was significantly higher in the calcium-treated group. Compared with sevelamer-treated subjects, calcium-treated subjects showed a decrease in thoracic vertebral trabecular bone attenuation (p = 0.01) and a trend toward decreased cortical bone attenuation. More than 30% of calcium-treated subjects experienced a 10% or more decrease in trabecular and cortical bone attenuation. On study, sevelamer-treated subjects had higher concentrations of total and bone-specific alkaline phosphatase, osteocalcin, and PTH (p < 0.001). When used to correct hyperphosphatemia, calcium salts lead to a reduction in thoracic trabecular and cortical bone attenuation. Calcium salts may paradoxically decrease BMD in hemodialysis patients.

    Title Insulin Resistance in Critically Ill Patients with Acute Renal Failure.
    Date August 2005
    Journal American Journal of Physiology. Renal Physiology
    Excerpt

    Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort (n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period (P = 0.008, adjusted P = 0.013). In the larger PICARD cohort (n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 +/- 508 vs. 234 +/- 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 +/- 30.0 vs. 11.7 +/- 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 +/- 498 vs. 1,470 +/- 581 microg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.

    Title Frequent Hemodialysis and Psychosocial Function.
    Date July 2005
    Journal Seminars in Dialysis
    Excerpt

    Studies suggest that more frequent hemodialysis (HD; short daily and long nocturnal dialysis) may be associated with a variety of clinical benefits, including improvement in blood pressure, anemia, and hyperphosphatemia, regression of left ventricular hypertrophy, and reduced rates of hospitalization. Whether these clinical benefits are paralleled by improvements in health-related quality of life (HRQOL) has been unclear. In addition, the psychosocial burden of more intensive HD schedules has not been critically evaluated. Recent reports have suggested beneficial effects of frequent HD on global HRQOL, dialysis-related and uremic symptoms, patient satisfaction, and psychosocial burden. However, the interpretation of many of these studies is restricted by limitations in study design, follow-up, and generalizability. This article reviews the current literature focusing on psychosocial and HRQOL effects of frequent HD and suggests future directions for research in this important area.

    Title Increased Prevalence of Subclinical and Clinical Hypothyroidism in Persons with Chronic Kidney Disease.
    Date June 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: Previous studies have suggested a higher prevalence of thyroid abnormalities in persons with end-stage renal disease. However, little is known regarding the epidemiology of thyroid disorders in persons with less severe kidney dysfunction. METHODS: We used data from the Third National Health and Nutrition Examination Survey to examine the prevalence of hypothyroidism (clinical and subclinical) at different levels of estimated glomerular filtration rate (GFR). We used multivariable logistic regression to evaluate the association between GFR and prevalent hypothyroidism. RESULTS: Among 14,623 adult participants with serum creatinine and thyroid function test results, the mean age was 48.7 years, and 52.6% were women. The prevalence of hypothyroidism increased with lower levels of GFR (in units of mL/min/1.73 m(2)), occurring in 5.4% of subjects with GFR >/=90, 10.9% with GFR 60-89, 20.4% with GFR 45-59, 23.0% with GFR 30-44, and 23.1% with GFR <30 (P < 0.001 for trend). Overall, 56% of hypothyroidism cases were considered subclinical. Compared with GFR >/=90 mL/min/1.73 m(2), reduced GFR was associated with an increased risk of hypothyroidism, after adjusting for age, gender, and race/ethnicity: adjusted odds ratio 1.07 (95% confidence interval: 0.86-1.32) for GFR 60-89, 1.57 (1.11-2.22) for GFR 45-59, 1.81 (1.04-3.16) for GFR 30-44, and 1.97 (0.69-5.61) for GFR <30 mL/min/1.73 m(2) (P= 0.008 for trend). CONCLUSION: Among a nationally representative sample of adults, reduced glomerular filtration rate was associated with a higher prevalence of hypothyroidism, with many subclinical cases. Future studies are needed to determine the potential adverse effects of subclinical and clinical hypothyroidism in persons with chronic kidney disease.

    Title Calcification or Classification?
    Date June 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Title Suicide in the United States End-stage Renal Disease Program.
    Date June 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Although depression and dialysis withdrawal are relatively common among individuals with ESRD, there have been few systematic studies of suicide in this population. The goals of this study were to compare the incidence of suicide with national rates and to contrast the factors associated with suicide with those associated with withdrawal in persons with ESRD. All individuals who were aged 15 yr and older and initiated dialysis between April 1, 1995, and November 30, 2000, composed the analytic cohort. Patients were censored at the time of death, transplantation, or October 31, 2001. Death as a result of suicide in the ESRD population and the general US population was ascertained from the Death Notification Form and the Centers for Disease Control and Prevention, respectively. Standardized incidence ratios for suicide among patient subgroups were computed using national data from the year 2000 as the reference population. The crude suicide rate from 1995 to 2001 was 24.2 suicides per 100,000 patient-years, and the overall standardized incidence ratio for suicide was 1.84 (95% confidence interval, 1.50 to 2.27). In multivariable models, age > or =75 yr, male gender, white or Asian race, geographic region, alcohol or drug dependence, and recent hospitalization with mental illness were significant independent predictors of death as a result of suicide. Persons with ESRD are significantly more likely to commit suicide than persons in the general population. Although relatively rare, risk assessment can be used to identify patients for whom counseling and other interventions might be beneficial.

    Title Serum Blood Urea Nitrogen As an Independent Marker of Subsequent Mortality Among Patients with Acute Coronary Syndromes and Normal to Mildly Reduced Glomerular Filtration Rates.
    Date June 2005
    Journal Journal of the American College of Cardiology
    Excerpt

    OBJECTIVES: We hypothesized that elevated blood urea nitrogen (BUN) would be associated with adverse outcomes independent of serum creatinine (sCr)-based estimates of kidney function in patients with acute coronary syndromes (ACS). BACKGROUND: Although lower glomerular filtration rates (GFR) have prognostic significance among patients with ACS, estimates of GFR based on sCr may perform less accurately among patients with milder kidney dysfunction. In this population in particular, BUN, which can reflect increased proximal tubular reabsorption in addition to decreased GFR, may have independent prognostic value. METHODS: Data were drawn from 9,420 patients with unstable coronary syndromes from Orbofiban in Patients With Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI)-16, a trial that excluded patients with sCr >1.6 mg/dl or estimated creatinine clearance <40 ml/min. RESULTS: Patients with elevated BUN were older, had a higher prevalence of comorbidities, and had higher heart rates, lower systolic blood pressures, and an abnormal Killip class more often on admission. In univariate analyses, as well as in stratified and multivariable analyses including sCr-based estimates of GFR as a covariate, a stepwise increase in mortality occurred with increasing BUN (multivariable hazard ratio with BUN 20 to 25 mg/dl 1.9, 95% confidence interval 1.3 to 2.6; with BUN >/=25 mg/dl 3.2 [95% confidence interval 2.2 to 4.7]) compared with BUN </=20 mg/dl. A higher BUN was also associated with increased mortality among strata of troponin-I, B-type natriuretic peptide, and C-reactive protein concentrations. CONCLUSIONS: Among patients with unstable coronary syndromes and predominantly normal or mildly reduced GFR, an elevated BUN is associated with increased mortality, independent of sCr-based estimates of GFR and other biomarkers.

    Title Influence of Race on Kidney Transplant Outcomes Within and Outside the Department of Veterans Affairs.
    Date June 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Inferior outcomes after kidney transplantation among African Americans are poorly understood. It was hypothesized that unequal access to medical care among transplant recipients might contribute to worse posttransplantation outcomes among African Americans and that racial disparities in kidney transplant outcomes would be less pronounced among patients who receive health care within versus outside the Department of Veterans Affairs (VA), because eligible veterans who receive care within the VA are entitled to receive universal access to care, including coverage of prescription drugs. A study cohort of 79,361 patients who were undergoing their first kidney transplant in the United States between October 1, 1991, and October 31, 2000, was assembled, with follow-up data on graft survival obtained through October 31, 2001. After multivariable proportional hazards adjustment for a wide range of recipient and donor characteristics, African-American patients were at increased risk for graft failure compared with non-African-American patients (relative risk [RR] 1.31; 95% confidence interval [CI] 1.26 to 1.36). African-American race was associated with a similarly increased risk for graft failure among patients who were VA users (RR 1.31; 95% CI 1.11 to 1.54) and non-VA users (RR 1.31; 95% CI 1.26 to 1.36). In conclusion, racial disparities in kidney transplant outcomes seem to persist even in a universal access-to-care system such as the VA. Reasons for worse outcomes among African Americans require further investigation.

    Title Achieving Nkf-k/doqi Bone Metabolism and Disease Treatment Goals with Cinacalcet Hcl.
    Date June 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQItrade mark) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipartrade mark) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca x P) was investigated in subjects on dialysis with secondary HPT. METHODS: Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180 mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca x P levels. RESULTS: Cinacalcet-treated subjects were more likely to achieve a mean iPTH </=300 pg/mL (31.8 pmol/L) than were control subjects on traditional therapy (56% vs. 10%, P < 0.001). Cinacalcet-treated subjects were more likely to achieve concentrations of serum calcium within 8.4 to 9.5 mg/dL (2.10-2.37 mmol/L) and serum phosphorus within 3.5 to 5.5 mg/dL (1.13-1.78 mmol/L) than were control subjects (49% vs. 24% and 46% vs. 33%, P < 0.001 for each). Cinacalcet also improved achievement of Ca x P < 55 mg(2)/dL(2) (4.44 mmol(2)/L(2)) and concurrent achievement of Ca x P < 55 mg(2)/dL(2) (4.44 mmol(2)/L(2)) and iPTH </=300 pg/mL (31.8 pmol/L) (65% vs. 36% and 41% vs. 6%, P < 0.001 for each). CONCLUSION: In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca x P.

    Title Race/ethnicity and Disease Severity in Iga Nephropathy.
    Date June 2005
    Journal Bmc Nephrology
    Excerpt

    BACKGROUND: Relatively few U.S.-based studies in chronic kidney disease have focused on Asian/Pacific Islanders. Clinical reports suggest that Asian/Pacific Islanders are more likely to be affected by IgA nephropathy (IgAN), and that the severity of disease is increased in these populations. METHODS: To explore whether these observations are borne out in a multi-ethnic, tertiary care renal pathology practice, we examined clinical and pathologic data on 298 patients with primary glomerular lesions (IgAN, focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease) at the University of California San Francisco Medical Center from November 1994 through May 2001. Pathologic assessment of native kidney biopsies with IgAN was conducted using Haas' classification system. RESULTS: Among individuals with IgAN (N = 149), 89 (60%) were male, 57 (38%) white, 53 (36%) Asian/Pacific Islander, 29 (19%) Hispanic, 4 (3%) African American and 6 (4%) were of other or unknown ethnicity. The mean age was 37 +/- 14 years and median serum creatinine 1.7 mg/dL. Sixty-six patients (44%) exhibited nephrotic range proteinuria at the time of kidney biopsy. The distributions of age, gender, mean serum creatinine, and presence or absence of nephrotic proteinuria and/or hypertension at the time of kidney biopsy were not significantly different among white, Hispanic, and Asian/Pacific Islander groups. Of the 124 native kidney biopsies with IgAN, 10 (8%) cases were classified into Haas subclass I, 12 (10%) subclass II, 23 (18%) subclass III, 30 (25%) subclass IV, and 49 (40%) subclass V. The distribution of Haas subclass did not differ significantly by race/ethnicity. In comparison, among the random sample of patients with non-IgAN glomerular lesions (N = 149), 77 (52%) patients were male, 51 (34%) white, 42 (28%) Asian/Pacific Islander, 25 (17%) Hispanic, and 30 (20%) were African American. CONCLUSIONS: With the caveats of referral and biopsy biases, the race/ethnicity distribution of IgAN differs significantly from that of other major glomerulonephridities. However, among individuals undergoing native kidney biopsy, we see no evidence of a race/ethnicity association with severity of disease in IgAN by clinical and IgAN-specific histopathologic criteria. Further studies are needed to identify populations at higher risk for progressive disease in IgAN.

    Title Chronic Kidney Disease, Cardiovascular Risk, and Response to Angiotensin-converting Enzyme Inhibition After Myocardial Infarction: the Survival And Ventricular Enlargement (save) Study.
    Date May 2005
    Journal Circulation
    Excerpt

    BACKGROUND: Persons with end-stage renal disease and those with lesser degrees of chronic kidney disease (CKD) have an increased risk of death after myocardial infarction (MI) that is not fully explained by associated comorbidities. Future cardiovascular event rates and the relative response to therapy in persons with mild to moderate CKD are not well characterized. METHODS AND RESULTS: We calculated the estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease method in 2183 Survival And Ventricular Enlargement (SAVE) trial subjects. SAVE randomized post-MI subjects (3 to 16 days after MI) with left ventricular ejection fraction < or =40% and serum creatinine <2.5 mg/dL to captopril or placebo. Cox proportional hazards models were used to evaluate the relative hazard rates for death and cardiovascular events associated with reduced eGFR. Subjects with reduced eGFR were older and had more extensive comorbidities. The multivariable adjusted risk ratio for total mortality associated with reduced eGFR from 60 to 74, 45 to 59, and <45 mL x min(-1) x 1.73 m(-2) (compared with eGFR > or =75 mL x min(-1) x 1.73 m(-2)) was 1.11 (0.86 to 1.42), 1.24 (0.96 to 1.60) and 1.81 (1.32 to 2.48), respectively (P for trend =0.001). Similar adjusted trends were present for CV mortality (P=0.001), recurrent MI (P=0.017), and the combined CV mortality and morbidity outcome (P=0.002). The absolute benefit of captopril tended to be greater in subjects with CKD: 12.4 versus 5.5 CV events prevented per 100 subjects with (n=719) and without (n=1464) CKD, respectively. CONCLUSIONS: CKD was associated with a heightened risk for all major CV events after MI, particularly among subjects with an estimated glomerular filtration rate <45 mL x min(-1) x 1.73 m(-2). Randomization to captopril resulted in a reduction of CV events irrespective of baseline kidney function.

    Title Validation of the Kidney Disease Quality of Life (kdqol) Cognitive Function Subscale.
    Date April 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: Formal cognitive function testing is cumbersome, and no self-administered instruments for estimating cognitive function in persons with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been validated. The goal of this study was to determine the validity of the Kidney Disease Quality of Life Cognitive Function scale (KDQOL-CF) for the assessment of cognitive impairment in persons with kidney disease. METHODS: We administered the KDQOL-CF to 157 subjects, 79 with ESRD and 78 with CKD participating in a cross-sectional study of cognitive function. Scores on the Modified Mini-Mental State Exam (3MS) were considered the gold standard measure of global cognitive function. Performance characteristics of the KDQOL-CF were assessed using correlation coefficients, Bland-Altman plots, and receiver operating characteristic curves. RESULTS: Median scores on the KDQOL-CF were 73 (interquartile range 60-87) for subjects with ESRD and 87 (interquartile range 73-100) for subjects with CKD (P < 0.0001). Scores on the KDQOL-CF were directly correlated with scores on the 3MS (r = 0.31, P = 0.0001). Defining global cognitive impairment as a 3MS score < 80, a cut-point of 60 on the KDQOL-CF accurately classified 76% of subjects, with 52% sensitivity and 81% specificity. On multivariable analysis, cerebral and peripheral vascular disease, benzodiazepine use, and higher serum phosphorus concentrations were associated with lower KDQOL-CF scores, while beta blocker use, education, and higher serum albumin concentrations were associated with higher KDQOL-CF scores. CONCLUSION: The KDQOL-CF is a valid instrument for estimating cognitive function in patients with CKD and ESRD. KDQOL-CF screening followed by 3MS testing in selected individuals may prove to be an effective and efficient strategy for identifying cognitive impairment in patients with kidney disease.

    Title The Influence of Patient- and Facility-specific Factors on Nutritional Status and Survival in Hemodialysis.
    Date April 2005
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    BACKGROUND: Parameters of nutritional status, including serum albumin, serum creatinine, and body mass index (BMI), are powerful predictors of mortality and hospitalization in patients with end stage renal disease (ESRD). Patient-specific characteristics and facility-related practice patterns modify certain parameters of nutritional status. We aimed to determine whether patient and facility characteristics modify the risk profiles associated with malnutrition in hemodialysis patients. METHODS: We analyzed data on 5,234 prevalent hemodialysis patients from the Dialysis Morbidity and Mortality Study (DMMS) Wave 1 for whom information on demographic, clinical, nutritional, and facility-related characteristics were available. We evaluated the associations among facility characteristics and serum albumin, serum creatinine, and BMI, adjusting for the effects of age, sex, race/ethnicity, diabetes, and dialysis vintage. We determined correlates of mortality and hospitalization, focusing on nutritional parameters, facility effects, and the interactions among patient-specific and facility-specific characteristics, albumin, creatinine, and BMI. RESULTS: Serum albumin was lower with older age, diabetes, nonblack race, and hemodialysis using a catheter. Serum albumin was higher with annual vascular access surveillance, higher BMI among women, higher urea reduction ratio, among patients in whom dialyzers were reprocessed (particularly with bleach), among dialysis units in which water purification was used, and when vascular access blood flow rates were > or =350 mL/min. Overall survival was decreased with lower albumin, creatinine, and BMI. There were interactions among albumin, age, and vintage. Whereas lower serum albumin concentrations consistently were associated with an increased risk of death, the differences were attenuated among older patients and accentuated among patients of longer vintage. CONCLUSION: Some facility-specific factors are associated with nutritional parameters including serum albumin, serum creatinine, and BMI. The associations of nutritional parameters with mortality and hospitalization vary by age, sex, and vintage but not by facility-specific factors, including those associated with the nutritional parameters themselves.

    Title Spectrum of Acute Renal Failure in the Intensive Care Unit: the Picard Experience.
    Date February 2005
    Journal Kidney International
    Excerpt

    BACKGROUND: Acute renal failure (ARF) in the critically ill is associated with extremely high mortality rates. Understanding the changing spectrum of ARF will be necessary to facilitate quality improvement efforts and to design successful interventional trials. METHODS: We conducted an observational cohort study of 618 patients with ARF in intensive care units at five academic medical centers in the United States. Participants were required to sign (or have a proxy sign) informed consent for data collection. A comprehensive data collection instrument captured more than 800 variables, most on a daily basis, throughout the course of ARF. Patient characteristics, dialysis status, and major outcomes were determined and stratified by clinical site. RESULTS: The mean age was 59.5 years, 41% were women, and 20% were of minority race or ethnicity. There was extensive comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29% had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was accompanied by extrarenal organ system failure in most patients, even those who did not require dialysis. Three hundred and ninety-eight (64%) patients required dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or nonrecovery of renal function was 50%. The median hospital length of stay was 25 days (26 days, excluding patients who died). CONCLUSION: There is a changing spectrum of ARF in the critically ill, characterized by a large burden of comorbid disease and extensive extrarenal complications, obligating the need for dialysis in the majority of patients. There is wide variation across institutions in patient characteristics and practice patterns. These differences highlight the need for additional multicenter observational and interventional studies in ARF.

    Title "renalism": Inappropriately Low Rates of Coronary Angiography in Elderly Individuals with Renal Insufficiency.
    Date February 2005
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Higher risk patients (including the elderly) receive more conservative therapy for cardiovascular diseases, even though the relative benefits of therapy tend to be greater. The perceived risk of radiocontrast-associated nephrotoxicity may influence the provision of coronary angiography and subsequent revascularization, especially among individuals with chronic kidney disease (CKD). The aim of this study was to determine whether there is excessive variation in the provision of coronary angiography after acute myocardial infarction on the basis of the presence of CKD and whether there is an association between angiography and mortality. Elderly (age 65 to 89 yr) individuals with acute myocardial infarction from the Cooperative Cardiovascular Project were classified by the presence or absence of CKD (defined as a baseline serum creatinine of 1.5 to 5.0 mg/dl). In CKD patients, the propensity to undergo coronary angiography was determined and the effect of coronary angiography on mortality was estimated using multivariable logistic regression and stratification. Mortality was significantly higher with CKD (52.6 versus 26.4%). Fewer patients with CKD underwent coronary angiography (25.2 versus 46.8%) despite the observation that a similar proportion of patients were deemed appropriate for angiography by standard, published criteria. When limiting the analysis to CKD patients who are considered appropriate, the multivariable estimate of the odds of death associated with coronary angiography was 0.58 (95% confidence interval, 0.50 to 0.67). With adjustment using propensity scores, the odds ratio averaged across propensity score quintiles was 0.62 (95% confidence interval, 0.54 to 0.70). Results were qualitatively similar when patients were stratified by CKD stage IV (estimated GFR <30 ml/min per 1.73 m(2)). There is a large relative decrease in utilization of coronary angiography among patients with CKD. Alteration in practice because of an aversion to the risk of radiocontrast-associated nephrotoxicity ("renalism") is inappropriate, even if the true relative benefit of invasive strategies is a fraction of what is estimated here.

    Title Theophylline for the Prevention of Radiocontrast Nephropathy: a Meta-analysis.
    Date February 2005
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Radiocontrast nephropathy is a common cause of acute renal failure in hospitalized patients. Several studies have examined the capacity of theophylline or aminophylline to prevent radiocontrast nephropathy, with conflicting results. We conducted a meta-analysis of published randomized controlled trials to determine if the pre-procedural administration of theophylline or aminophylline prevents radiocontrast-induced declines in kidney function. METHODS: We searched MEDLINE, EMBASE, the Cochrane Collaboration Database, bibliographies of retrieved articles, and consulted with experts to identify relevant studies. Randomized controlled trials of theophylline or aminophylline in hospitalized patients receiving radiocontrast were included. Studies were excluded if they did not report changes in serum creatinine or creatinine clearance within 48 h after radiocontrast exposure. RESULTS: Seven randomized controlled trials satisfied all inclusion criteria and were included in the analysis (pooled sample size n = 480). The difference in mean change in serum creatinine was 11.5 micromol/l (95% confidence intervals 5.3-19.4 micromol/l, P = 0.004) lower in the theophylline- or aminophylline-treated groups than controls. One participant (0.6%) required dialysis. CONCLUSIONS: Prophylactic administration of theophylline or aminophylline appears to protect against radiocontrast-induced declines in kidney function. Whether these agents reduce the proportion of patients who experience large decrements in serum creatinine concentration, or require dialysis, is unknown.

    Title Effects of Sevelamer and Calcium-based Phosphate Binders on Uric Acid Concentrations in Patients Undergoing Hemodialysis: a Randomized Clinical Trial.
    Date February 2005
    Journal Arthritis and Rheumatism
    Excerpt

    OBJECTIVE: Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders. METHODS: Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest. RESULTS: Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02). CONCLUSION: In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.

    Title Diminishing Significance of Hla Matching in Kidney Transplantation.
    Date February 2005
    Journal American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
    Excerpt

    To determine trends in the significance of HLA matching and other risk factors in kidney transplantation, we analyzed data on graft survival in a consecutive sample of 33 443 transplant recipients who received deceased donor kidneys from December 1994 to December 1998 with a mean follow-up time of 2.2 years. HLA matching and other risk factors (peak panel reactive antibody, donor age, sex and cause of death, cold ischemia time, donor and recipient body size) were examined. Mean likelihood ratios of models, fit with and without each variable of interest, were calculated by generating bootstrapped samples from each single year cohort. Pooled censored and uncensored graft survival rates were 90.6% and 89.9% at 1 year, 85.8% and 84.5% at 2 years, and 80.7% and 78.6% at 3 years. HLA matching declined in significance while other factors retained similar levels of statistical significance over the four yearly cohorts. With evolving clinical practice, including the provision of safer and more potent immunosuppressive therapy, the significance of HLA matching has diminished. Non-immunologic factors continue to impede more marked improvements in long-term graft survival. Recognizing these trends, organ allocation algorithms may need to be revised.

    Title Cognitive Impairment in Chronic Kidney Disease.
    Date December 2004
    Journal Journal of the American Geriatrics Society
    Excerpt

    OBJECTIVES: To assess the prevalence of cognitive impairment in persons with chronic kidney disease (CKD) and its relation to the severity of CKD. DESIGN: Cross-sectional study. SETTING: University-affiliated ambulatory nephrology and dialysis practices. PARTICIPANTS: Eighty subjects with CKD Stages III and IV not requiring dialysis (CKD) and 80 subjects with CKD Stage V on hemodialysis (end-stage renal disease (ESRD)) with a mean age+/-standard deviation of 62.5+/-14.3. MEASUREMENTS: Three standardized cognitive tests, the Modified Mini-Mental State Examination (3MS), Trailmaking Test B (Trails B), and California Verbal Learning Trial (CVLT). Glomerular filtration rate was estimated in subjects with CKD using the six-variable Modification of Diet in Renal Disease equation. RESULTS: There was a graded relation between cognitive function and severity of CKD. Mean scores on the 3MS, Trails B, and CVLT immediate and delayed recall were significantly worse for subjects with ESRD than for subjects with CKD or published norms (P<.001 for all comparisons). Scores on the Trails B (P<.001) and CVLT immediate (P=.01) and delayed (P<.001) recall were significantly worse for subjects with CKD not requiring dialysis than for published norms. In addition, the fraction of subjects with impairment on the 3MS and Trails B increased with decreasing kidney function. CONCLUSION: Cognitive impairment is associated with the severity of kidney disease. Further studies are needed to determine the reasons for cognitive impairment in subjects with CKD and ESRD.

    Title Vector Length As a Proxy for the Adequacy of Ultrafiltration in Hemodialysis.
    Date October 2004
    Journal Kidney International
    Excerpt

    BACKGROUND: Evaluation of dialysis adequacy has focused on parameters of solute (principally urea) clearance. Relatively little attention has been paid to the adequacy of ultrafiltration. At a given phase angle, the bioimpedance vector length reflects the degree of tissue hydration, as the vector lengthens with ultrafiltration. METHODS: We determined the relative risk of death associated with different bioimpedance vector lengths in a 3009 patient hemodialysis cohort using proportional hazards regression. RESULTS: The mean phase angle was 4.8 degrees, and the mean vector length 300 +/- 70 ohm/m (range 140 to 630 ohm/m). Vector length was much longer in women than men (mean 340 vs. 270 ohm/m) and significantly longer in African Americans and patients without diabetes. Adjusted for the effects of age, gender, race, diabetes, vintage, weight, albumin, prealbumin, creatinine, hemoglobin, ferritin, and dialysis dose, the relative risk (RR) of death was 0.75 (95% CI 0.57 to 0.88) per 100 ohm/m decrease in vector length. The effect of vector length on RR was somewhat more pronounced among men (vector length x gender interaction, P= 0.07). Considering vector length of 300 to 350 ohm/m as the referent category, the RRs of death were 1.54 (95% CI 1.08 to 2.21) and 2.83 (95% CI 1.55 to 5.14) for patients with vector length 200 to 250 and <200 ohm/m, respectively. CONCLUSION: Shorter predialysis bioimpedance vectors, indicating greater soft tissue hydration, were associated with diminished survival in hemodialysis patients. These findings validate clinical observations linking longevity to maintenance of dry body weight.

    Title Plasma Cytokine Levels Predict Mortality in Patients with Acute Renal Failure.
    Date October 2004
    Journal Kidney International
    Excerpt

    BACKGROUND: Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness. RESULTS: When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients. CONCLUSION: There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

    Title Incorporating Recipient Choice in Kidney Transplantation.
    Date October 2004
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Despite the acute shortage of cadaveric organs for kidney transplantation, more than 10% of cadaveric kidneys are discarded each year because of marginal quality. Transplant recipients' access to these kidneys and to information about their quality is limited. A Monte Carlo model was developed to simulate the operations of an organ procurement organization over a 10-yr period. Donor and recipient characteristics were generated from the United States Renal Data System. Kidneys were assigned one of five possible grades, which were determined by calculating the relative risk of graft failure associated with donor characteristics and HLA matching for every donor-candidate pair. Modeled were recipient decisions to accept or reject a kidney on the basis of the relative change in quality-adjusted life years (QALY). Compared were the United Network of Organ Sharing (UNOS) policy, the UNOS expanded donor criteria policy, two benchmark policies (one equity driven and the other efficiency driven), and a hybrid policy that incorporated recipient choice into the UNOS algorithm. Sensitivity analyses for major input variables were performed. Compared with UNOS, an algorithm that incorporated recipient choice predicted a 6% increase in QALY, a 12% decrease in median waiting time, a 39% increase in the likelihood of transplantation, and a 56% reduction in the number of discarded kidneys. Benefits were observed across categories of age, gender, and race. Incorporating recipient choice in kidney transplantation would improve equity, efficiency, and QALY of the end-stage renal disease population.

    Title Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization.
    Date September 2004
    Journal The New England Journal of Medicine
    Excerpt

    BACKGROUND: End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. METHODS: We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. RESULTS: The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern. CONCLUSIONS: An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency.

    Title Determinants of Progressive Vascular Calcification in Haemodialysis Patients.
    Date September 2004
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups. METHODS: We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52). RESULTS: Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated. CONCLUSION: Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.

    Title On the Relative Safety of Parenteral Iron Formulations.
    Date September 2004
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Intravenous iron is usually required to optimize the correction of anaemia in persons with advanced chronic kidney disease and end-stage renal disease. Randomized clinical trials may have insufficient power to detect differences in the safety profiles of specific formulations. METHODS: We obtained data from the US Food and Drug Administration on reported adverse drug events (ADEs) related to the provision of three formulations of intravenous iron during 1998-2000. We estimated the relative risks [odds ratios (OR)] of ADEs associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran using 2 x 2 tables. RESULTS: The total number of reported parenteral iron-related ADEs was 1981 among approximately 21,060,000 doses administered, yielding a rate of 9.4 x 10(-5), or approximately 94 per million. Total major ADEs were significantly increased among recipients of higher molecular weight iron dextran (OR 5.5, 95% CI 4.9-6.0) and sodium ferric gluconate complex (OR 6.2, 95% CI 5.4-7.2) compared with recipients of lower molecular weight iron dextran. We observed significantly higher rates of life-threatening ADEs, including death, anaphylactoid reaction, cardiac arrest and respiratory depression among users of higher molecular weight compared with lower molecular weight iron dextran. There was insufficient power to detect differences in life-threatening ADEs when comparing lower molecular weight iron dextran with sodium ferric gluconate complex. CONCLUSIONS: Parenteral iron-related ADEs are rare. Using observational data, overall and most specific ADE rates were significantly higher among recipients of higher molecular weight iron dextran and sodium ferric gluconate complex than among recipients of lower molecular weight iron dextran. These data may help to guide clinical practice, as head-to-head clinical trials comparing different formulations of intravenous iron have not been conducted.

    Title Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis.
    Date September 2004
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

    Title Acute Renal Failure Definitions and Classification: Time for Change?
    Date September 2004
    Journal Journal of the American Society of Nephrology : Jasn
    Title Valvular Calcification in Hemodialysis Patients Randomized to Calcium-based Phosphorus Binders or Sevelamer.
    Date September 2004
    Journal The Journal of Heart Valve Disease
    Excerpt

    BACKGROUND AND AIM OF THE STUDY: Valvular calcification is common in patients with end-stage renal disease, and is associated with an unfavorable prognosis. It was hypothesized that sevelamer, a non-calcium-based phosphorus binder, might attenuate the progression of valvular calcification. METHODS: Two hundred subjects on maintenance hemodialysis received either sevelamer or calcium-based phosphorus binders. To assess the extent of calcification, 186 subjects underwent baseline electron beam tomography (EBT) of the coronary arteries, aorta and mitral and aortic valves, and 132 had follow up EBT scans at week 52. Changes in valvular calcification and combined valvular/vascular calcification were monitored and compared. RESULTS: At baseline, mitral valve calcification was seen in 46% of subjects, aortic valve calcification in 33%. Most subjects with zero values at baseline failed to progress over one year. Aortic valve calcification was significantly increased in calcium-treated subjects. Changes in mitral valve calcification, and combined mitral + aortic valve calcification were less in sevelamer-treated than in calcium-treated subjects, but not significantly so. When combining valvular and vascular calcification, the median (10%, 90%) change in sevelamer-treated subjects was significantly lower than in calcium-treated subjects (6, -5084 to 1180 versus 81, -1150 to 2944, p = 0.04). The effect of sevelamer remained significant after adjustment for baseline calcification and the time-averaged calcium-phosphorus product, and was independent of the calcium preparation (acetate versus carbonate), geographic region (US versus Europe), LDL- or HDL-cholesterol, C-reactive protein and statin use. Significantly more sevelamer-treated subjects experienced an arrest (45 versus 28%, p = 0.047) or regression (26 versus 10%, p = 0.02) in total valvular and vascular calcification. CONCLUSION: Sevelamer arrested the progression of valvular and vascular calcification in almost 50% of hemodialysis subjects. Sevelamer treatment, plus intensive control of calcium and phosphorus levels, may attenuate progression of, or achieve regression in, cardiac valvular calcification.

    Title Association of Body Size with Outcomes Among Patients Beginning Dialysis.
    Date August 2004
    Journal The American Journal of Clinical Nutrition
    Excerpt

    BACKGROUND: Although obesity confers an increased risk of mortality in the general population, observational reports on the dialysis population have suggested that obesity is associated with improved survival. These reports have generally not examined extremely high values of body mass index (BMI; in kg/m(2)), survival >1 y, or alternative measures of adiposity. OBJECTIVE: We sought to clarify the relation between body size and outcomes among a large cohort of patients beginning dialysis. DESIGN: Data on 418 055 patients beginning dialysis between 1 April 1995 and 1 November 2000 were analyzed by using US Renal Data System data. BMI was divided into 8 categories in increments of 3 units, ranging from < 19 to > or =37, and the relation between survival and BMI was examined by using proportional hazards regression with adjustment for demographic, laboratory, and comorbidity data. RESULTS: High BMI was associated with increased survival in this cohort, even at extremely high BMI, after adjustment, and over a 2-y average follow-up time. This was true for whites, African Americans, and Hispanics but not for Asians. High BMI was also associated with a reduced risk of hospitalization and a lower rate of mortality in all mortality categories. Alternative estimates of adiposity, including the Benn index and estimated fat mass, yielded similar results, and adjustments for lean body mass did not substantially alter the findings. CONCLUSIONS: High BMI is not associated with increased mortality among patients beginning dialysis. This finding does not appear to be a function of lean body mass and, although modified by certain patient characteristics, it is a robust finding.

    Title Inflammatory Markers Are Unrelated to Physical Activity, Performance, and Functioning in Hemodialysis.
    Date August 2004
    Journal Advances in Renal Replacement Therapy
    Excerpt

    OBJECTIVE: To determine the associations among dietary intake and inflammatory cytokines with physical activity, function, and performance in maintenance dialysis patients. DESIGN: Cross-sectional analysis of cohort study. SETTING: University-affiliated dialysis units, general clinical research center. SUBJECTS: Multiethnic cohort of maintenance hemodialysis patients. MAIN OUTCOME MEASURES: Physical activity by accelerometry; physical performance by gait speed, stair climbing, and chair raising; physical functioning by the Medical Outcomes Study Short Form 36-item questionnaire subscale scores; and maximal and adjusted activity scores of human activity profile. RESULTS: Levels of inflammatory cytokines were uniformly high. Tumor necrosis factor-alpha was directly correlated with dietary protein and energy intake; no other cytokines were directly or inversely correlated with intake. Dietary intake was associated with physical activity, as expected, and not significantly associated with performance or function (with the exception of gait speed). There were no significant associations among inflammatory cytokines and physical activity, performance, or function. CONCLUSION: Although dietary intake and inflammation may independently influence traditional proxies of nutritional status, this analysis provides no evidence for a link between cytokines and physical activity, performance, or function in hemodialysis patients. More research is required to understand the role of cytokines in protein energy malnutrition and the mechanisms of wasting and functional decline in the dialysis population.

    Title Physical and Sexual Function in Women with Chronic Kidney Disease.
    Date July 2004
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    BACKGROUND: Cross-sectional studies suggest an association between functional status and chronic kidney disease (CKD). Whether physical function deteriorates with progression of CKD is unknown. METHODS: To determine associations among CKD, physical function, and sexual function in women, we conducted cross-sectional and longitudinal analyses of 2,761 women enrolled in the Heart and Estrogen/Progestin Replacement Study. Physical and sexual function were evaluated using the Duke Activity Status Index (DASI) and the Sexual Problems Scale of the Medical Outcomes Study, respectively. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease regression equation. In addition to analyses across the spectrum of GFR, CKD was categorized as mild (estimated GFR, 45 to 60 mL/min/1.73 m2), moderate (estimated GFR, 30 to 44 mL/min/1.73 m2), and severe (estimated GFR, <30 mL/min/1.73 m2) according to a modification of recently established classification guidelines. RESULTS: Mean age of study participants was 67 +/- 7 years, and mean estimated GFR was 61 +/- 14 mL/min/1.73 m2. In unadjusted analyses, mean baseline DASI score was 10 points lower in women with an estimated GFR less than 30 mL/min/1.73 m2 than in women with an estimated GFR of 60 mL/min/1.73 m2 or greater (P < 0.0001). Estimated GFR remained significantly associated with DASI score after multivariable adjustment. In longitudinal analyses, a decline in estimated GFR was associated with a significant decline in DASI score independent of baseline estimated GFR and other factors. There were no significant associations between estimated GFR and psychosocial aspects of sexual function. CONCLUSION: CKD is associated with impaired physical function, and a decline in estimated GFR is associated with a decline in physical function.

    Title Screening to Prevent Coronary Events or Screening to Detect Obstruction?
    Date July 2004
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title Prevention of Radiocontrast Nephropathy: Back to Basics.
    Date May 2004
    Journal Jama : the Journal of the American Medical Association
    Title Anthropometrically Estimated Total Body Water Volumes Are Larger Than Modeled Urea Volume in Chronic Hemodialysis Patients: Effects of Age, Race, and Gender.
    Date April 2004
    Journal Kidney International
    Excerpt

    BACKGROUND: The modeled volume of urea distribution (Vm) in intermittently hemodialyzed patients is often compared with total body water (TBW) volume predicted from population studies of patient anthropometrics (Vant). METHODS: Using data from the HEMO Study, we compared Vm determined by both blood-side and dialysate-side urea kinetic models with Vant as calculated by the Watson, Hume-Weyers, and Chertow anthropometric equations. RESULTS: Median levels of dialysate-based Vm and blood-based Vm agreed (43% and 44% of body weight, respectively). These volumes were lower than anthropometric estimates of TBW, which had median values of 52% to 55% of body weight for the three formulas evaluated. The difference between the Watson equation for TBW and modeled urea volume was greater in Caucasians (19%) than in African Americans (13%). Correlations between Vm and Vant determined by each of the three anthropometric estimation equations were similar; but Vant derived from the Watson formula had a slightly higher correlation with Vm. The difference between Vm and the anthropometric formulas was greatest with the Chertow equation, less with the Hume-Weyers formula, and least with the Watson estimate. The age term in the Watson equation for men that adjusts Vant downward with increasing age reduced an age effect on the difference between Vant and Vm in men. CONCLUSION: The findings show that kinetically derived values for V from blood-side and dialysate-side modeling are similar, and that these modeled urea volumes are lower by a substantial amount than anthropometric estimates of TBW. The higher values for anthropometry-derived TBW in hemodialyzed patients could be due to measurement errors. However, the possibility exists that TBW space is contracted in patients with end-stage renal disease (ESRD) or that the TBW space and the urea distribution space are not identical.

    Title A 43-year-old Woman with Chronic Renal Insufficiency.
    Date March 2004
    Journal Jama : the Journal of the American Medical Association
    Title The Effects of Sevelamer and Calcium Acetate on Proxies of Atherosclerotic and Arteriosclerotic Vascular Disease in Hemodialysis Patients.
    Date February 2004
    Journal American Journal of Nephrology
    Excerpt

    BACKGROUND: We recently determined that in hemodialysis patients, the use of calcium salts to correct hyperphosphatemia led to progressive coronary artery and aortic calcification as determined by sequential electron beam tomography (EBT) while the use of the non-calcium-containing binder sevelamer did not. Whether the specific calcium preparation (acetate vs. carbonate) might influence the likelihood of progressive calcification was debated. METHODS: To determine whether treatment with calcium acetate was specifically associated with hypercalcemia and progressive vascular calcification, we conducted an analysis restricted to 108 hemodialysis patients randomized to calcium acetate or sevelamer and followed for one year. RESULTS: The reduction in serum phosphorus was roughly equivalent with both agents (calcium acetate -2.5 +/- 1.8 mg/dl vs. sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53). Subjects given calcium acetate were more likely to develop hypercalcemia (defined as an albumin-corrected serum calcium > or =10.5 mg/dl) (36 vs. 13%, p = 0.015). Treatment with calcium acetate (mean 4.6 +/- 2.1 g/day - equivalent to 1.2 +/- 0.5 g of elemental calcium) led to a significant increase in EBT-determined calcification of the coronary arteries (mean change 182 +/- 350, median change +20, p = 0.002) and aorta (mean change 181 +/- 855, median change +73, p < 0.0001). These changes were similar in magnitude to those seen with calcium carbonate. There were no significant changes in calcification among sevelamer-treated subjects. CONCLUSION: Despite purported differences in safety and efficacy relative to calcium carbonate, calcium acetate led to hypercalcemia and progressive vascular calcification in hemodialysis patients.

    Title Analgesia in Patients with Esrd: a Review of Available Evidence.
    Date January 2004
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Moderate to severe pain frequently accompanies chronic diseases in general and end-stage renal disease (ESRD) in particular. Several analgesic agents and associated metabolites show altered pharmacokinetics in the presence of reduced glomerular filtration rate. Drug-related side effects may exacerbate symptoms frequently observed in persons with chronic kidney disease (CKD; eg, fatigue, nausea, vomiting, and constipation) or those often attributed to hemodialysis therapy (eg, orthostatic hypotension and impaired cognition). Persons with advanced CKD and ESRD are at increased risk for adverse effects of analgesic agents because of enhanced drug sensitivity, comorbid conditions, and concurrent medication use. Dose adjustment and avoidance of certain analgesics may be required in patients with advanced CKD and ESRD. We review the available evidence on pharmacokinetics and adverse drug effects of various analgesic agents commonly used in patients with advanced CKD and ESRD. Determining an optimal approach to the control of pain in patients with advanced CKD and ESRD will require additional research.

    Title Reasons for Non-enrollment in a Cohort Study of Arf: the Program to Improve Care in Acute Renal Disease (picard) Experience and Implications for a Clinical Trials Network.
    Date January 2004
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    BACKGROUND: Acute renal failure (ARF) is associated strongly with in-hospital mortality and morbidity. Previous clinical trials of ARF have been hampered by the heterogeneous population affected, difficulty defining ARF, delays in identification of ARF, and significant comorbid conditions, among other factors. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) phase I was a multicenter cohort study aimed to identify clinical characteristics and practice patterns associated with adverse and favorable outcomes in patients with ARF in intensive care units. Although PICARD used no interventions, signed informed consent was required of all study subjects or their proxies. RESULTS: Signed informed consent was obtained in 645 of 1,243 ARF episodes (52%). The fraction of patients not enrolled and reasons for non-enrollment varied widely across the 5 PICARD centers. Refusal by potential study subjects was infrequent, although the absence of family or proxy (15%) and refusal by family or proxy (18%) accounted for large fractions of non-enrolled subjects. Death (23%) and discharge (11%) before study personnel could evaluate patients were additional important reasons for non-enrollment. CONCLUSION: Understanding reasons for non-enrollment may help rationalize mortality and other outcome differences seen in clinical trials and cohort studies that require informed consent compared with historic reports of "all comers" with ARF.

    Title Slowing the Progression of Vascular Calcification in Hemodialysis.
    Date December 2003
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Hyperphosphatemia and secondary hyperparathyroidism are common complications of ESRD (chronic kidney disease stage 5) that, when untreated, may result in increased morbidity and mortality. Hyperphosphatemia and hypercalcemia have been associated with increased coronary artery calcification. Achieving control of serum phosphorus without increasing serum calcium is an important goal for patients with ESRD. Although calcium-based phosphate binders effectively reduce serum phosphorus and parathyroid hormone concentrations, these agents can lead to hypercalcemia and have been associated with increased vascular calcification. The phosphorus binder sevelamer was developed to overcome the limitations associated with the usual management of hyperphosphatemia and secondary hyperparathyroidism (i.e., mineral salts). Sevelamer, a nonabsorbable hydrogel, is as efficacious as calcium-based phosphate binders for reducing serum phosphorus but does not cause hypercalcemia or other adverse metabolic effects. Sevelamer also exhibits beneficial effects on lipids, consistently and significantly decreasing LDL cholesterol and increasing HDL cholesterol in most studies. In a head-to-head randomized clinical trial, sevelamer and calcium-based binders achieved similarly excellent phosphorus control, but the use of calcium-based binders led to significantly higher serum calcium concentrations and an increased incidence of hypercalcemia and unintended suppression of parathyroid hormone. Treatment with calcium-based binders also led to the progression of coronary artery and aortic calcification, whereas sevelamer attenuated or arrested progression. Strategies that use oral calcium and vitamin D in patients with ESRD should be reexamined, and the potential advantages of sevelamer should be considered when selecting a primary agent to reduce serum phosphorus in hemodialysis patients.

    Title The Chronic Renal Insufficiency Cohort (cric) Study: Design and Methods.
    Date August 2003
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Insights into end-stage renal disease have emerged from many investigations but less is known about the epidemiology of chronic renal insufficiency (CRI) and its relationship to cardiovascular disease (CVD). The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for progression of CRI and CVD among CRI patients and develop models to identify high-risk subgroups, informing future treatment trials, and increasing application of preventive therapies. CRIC will enroll approximately 3000 individuals at seven sites and follow participants for up to 5 yr. CRIC will include a racially and ethnically diverse group of adults aged 21 to 74 yr with a broad spectrum of renal disease severity, half of whom have diagnosed diabetes mellitus. CRIC will exclude subjects with polycystic kidney disease and those on active immunosuppression for glomerulonephritis. Subjects will undergo extensive clinical evaluation at baseline and at annual clinic visits and via telephone at 6 mo intervals. Data on quality of life, dietary assessment, physical activity, health behaviors, depression, cognitive function, health care resource utilization, as well as blood and urine specimens will be collected annually. (125)I-iothalamate clearances and CVD evaluations including a 12-lead surface electrocardiogram, an echocardiogram, and coronary electron beam or spiral CT will be performed serially. Analyses planned in CRIC will provide important information on potential risk factors for progressive CRI and CVD. Insights from CRIC should lead to the formulation of hypotheses regarding therapy that will serve as the basis for targeted interventional trials focused on reducing the burden of CRI and CVD.

    Title Longitudinal Study of Nutritional Status, Body Composition, and Physical Function in Hemodialysis Patients.
    Date April 2003
    Journal The American Journal of Clinical Nutrition
    Excerpt

    BACKGROUND: Cross-sectional studies have shown an association between the duration (y) of dialysis and nutritional status, providing evidence of wasting. OBJECTIVE: The aim was to determine the extent, pace, determinants, and optimal methods of assessing wasting in patients undergoing hemodialysis. DESIGN: Laboratory variables, body composition, and physical activity, function, and performance were tested 4 times over 1 y in 54 hemodialysis patients. Changes in repeated measures were evaluated, with adjustment for baseline differences by age, sex, race, diabetes status, and dialysis vintage (ie, time since initiation of dialysis). RESULTS: No significant changes in body weight, fat mass, lean body mass, or laboratory variables were observed. Phase angle, a bioelectrical impedance analysis-derived variable related to body cell mass, decreased significantly (linear estimate: -0.043 degrees /mo, or approximately 0.5 degrees/y; P = 0.001). Physical activity measured by accelerometry declined 3.4%/mo (P = 0.01). The Maximum Activity Score of the Human Activity Profile (HAP) also declined significantly (linear estimate: -0.50/mo, or approximately 6 points/y; P = 0.025). Higher interleukin 1beta (IL-1beta) concentrations were associated with a narrower phase angle (P = 0.004) and with a more rapid decline in phase angle with time (time x IL-1beta interaction, P = 0.01); similar effects of IL-1beta on physical activity were observed. Dietary protein and energy intakes were associated with changes in the HAP. CONCLUSIONS: Evidence of adverse changes in body composition and physical activity, function, and performance and of a modest influence of inflammation and dietary intake on these changes was observed in this cohort. Tools such as bioelectrical impedance analysis, accelerometry, and the HAP may be required to identify subtle changes.

    Title The Severity of Secondary Hyperparathyroidism in Chronic Renal Insufficiency is Gfr-dependent, Race-dependent, and Associated with Cardiovascular Disease.
    Date April 2003
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Secondary hyperparathyroidism (SHPT) is an important complication of end-stage renal disease. However, SHPT begins during earlier stages of chronic renal insufficiency (CRI), and little is known about risk factors for SHPT in this population. This study evaluated 218 patients in an ethnically diverse ambulatory nephrology practice at the University of California San Francisco during calendar years 1999 and 2000. Demographic data, comorbid diseases, medications, and laboratory parameters were collected, and independent correlates of intact parathyroid hormone (PTH) were identified by using multiple linear regression. The mean estimated GFR was 34 ml/min per 1.73 m(2) (10%-90% range, 13 to 61 ml/min per 1.73 m(2)); PTH was inversely related to GFR (P < 0.0001). The adjusted mean PTH was higher among African Americans and lower among Asian/Pacific Islanders compared with white patients (233 versus 95 versus 139 pg/ml; P < 0.0001). Moreover, among the 196 patients with GFR <60 ml/min per 1.73 m(2), the slope of GFR versus PTH was significantly steeper among African Americans than among white patients (10.6 versus 3.9 pg/ml per ml per min per 1.73 m(2); P = 0.01). After adjusting for age and diabetes, PTH was associated with a history of myocardial infarction (OR, 1.6; 95% CI, 1.1 to 2.3 per unit natural log PTH) and congestive heart failure (OR, 2.0; 95% CI, 1.3 to 2.9 per unit natural log PTH) and not associated with other co-morbid conditions. These factors should be considered when screening and managing SHPT in CRI.

    Title In Critically Ill Patients with Acute Renal Failure, Outcomes, Not Dollars, Should Drive Modality Choice.
    Date March 2003
    Journal Critical Care Medicine
    Title Elevations of Serum Phosphorus and Potassium in Mild to Moderate Chronic Renal Insufficiency.
    Date February 2003
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Reduced renal function is associated with a variety of biochemical abnormalities. However, the extent of these changes and their magnitude in relation to renal function is not well defined, especially among individuals with mild to moderate chronic renal insufficiency (CRI). METHODS: We analysed the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) data for 14722 adults aged >/=17 years with measurements of serum creatinine and all electrolytes including ionized calcium. General linear models were used to determine the relationship between mean concentrations of electrolytes and different levels of Cockcroft-Gault creatinine clearance (CrCl). Sample weights were used to produce weighted regression parameters. RESULTS: Changes in mean serum phosphorus and potassium concentration were evident at relatively modest reductions in CrCl (around 50 to 60 ml/min). Changes in the anion gap and mean levels of ionized calcium and bicarbonate were not apparent until CRI was advanced (CrCl </=20 ml/min). For example, compared with women with CrCl >80 ml/min, those with CrCl 60-50, 50-40, 40-30, 30-20 and </=20 ml/min had mean serum phosphorus concentrations that were higher by 0.1, 0.1, 0.2, 0.3 and 0.8 mg/dl (all P<0.05), and mean serum potassium concentrations that were higher by 0.1, 0.1, 0.1, 0.2 and 0.4 mmol/l (all P<0.05), respectively. These changes were independent of dietary intake and the use of angiotensin converting enzyme (ACE) inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Increases in serum phosphorus and potassium levels are apparent even among people with mild to moderate CRI. These findings should be broadly generalizable to the larger CRI population in the United States. Subtle elevations in serum phosphorus might contribute to the initiation and maintenance of secondary hyperparathyroidism, which is known to occur in mild to moderate CRI.

    Title Sevelamer Attenuates the Progression of Coronary and Aortic Calcification in Hemodialysis Patients.
    Date December 2002
    Journal Kidney International
    Excerpt

    BACKGROUND: Cardiovascular disease is frequent and severe in patients with end-stage renal disease. Disorders of mineral metabolism may contribute by promoting cardiovascular calcification. METHODS: We conducted a randomized clinical trial comparing sevelamer, a non-absorbed polymer, with calcium-based phosphate binders in 200 hemodialysis patients. Study outcomes included the targeted concentrations of serum phosphorus, calcium, and intact parathyroid hormone (PTH), and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography. RESULTS: Sevelamer and calcium provided equivalent control of serum phosphorus (end-of-study values 5.1 +/- 1.2 and 5.1 +/- 1.4 mg/dL, respectively, P = 0.33). Serum calcium concentration was significantly higher in the calcium-treated group (P = 0.002), and hypercalcemia was more common (16% vs. 5% with sevelamer, P = 0.04). More subjects in the calcium group had end-of-study intact PTH below the target of 150 to 300 pg/mL (57% vs. 30%, P = 0.001). At study completion, the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects (coronary arteries 36.6 vs. 0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01, respectively). The median percent change in coronary artery (25% vs. 6%, P = 0.02) and aortic (28% vs. 5%, P = 0.02) calcium score also was significantly greater with calcium than with sevelamer. CONCLUSIONS: Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.

    Title Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal Failure.
    Date December 2002
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. OBJECTIVE: To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. DESIGN: Cohort study conducted from October 1989 to September 1995. PATIENTS AND SETTING: A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. MAIN OUTCOME MEASURES: All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. RESULTS: Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. CONCLUSIONS: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

    Title Nephrology Consultation in Acute Renal Failure: Does Timing Matter?
    Date December 2002
    Journal The American Journal of Medicine
    Excerpt

    PURPOSE: Patients who develop acute renal failure in the intensive care unit (ICU) have extremely high rates of mortality and morbidity. The goals of this study were to identify correlates of the timing of nephrology consultation in acute renal failure, and to explore the relation between timing of consultation and outcomes. METHODS: We explored associations among timing of nephrology consultation and in-hospital mortality, lengths of hospital and ICU stay, and recovery of renal function in 215 ICU patients with acute renal failure at four U.S. teaching hospitals. We used multivariable logistic regression and propensity scores to adjust for confounding and selection effects. RESULTS: Nephrology consultation was delayed (>or=48 hours) in 61 patients (28%) (median time to consultation, 4 days). Lower serum creatinine levels (P <0.0001) and higher urine output (P = 0.002) were associated with delayed consultation. Delayed consultation was associated with increased mortality among dialyzed (31/42 [74%] vs. 50/103 [49%], P = 0.006) and nondialyzed patients (10/19 [53%] vs. 11/51 [22%], P = 0.01), and increases in lengths of hospital (median, 19 days vs. 16 days, P = 0.01) and ICU stay (17 days vs. 6 days, P <0.0001). The association between delayed consultation and mortality was attenuated by covariate adjustment, and was no longer statistically significant after adjustment for propensity score (odds ratio = 2.0; 95% confidence interval: 0.8 to 5.1). CONCLUSION: In acute renal failure, delayed nephrology consultation was associated with increased mortality and morbidity, whether or not dialysis was ultimately required. Using observational data, we cannot determine whether these findings reflect residual confounding, selection bias, adverse effects of delayed recognition of acute renal failure, or the benefits of nephrology consultation.

    Title Methodological Issues in Studying the Epidemiology of Mild to Moderate Chronic Renal Insufficiency.
    Date October 2002
    Journal Kidney International
    Excerpt

    There is increasing interest in studying the epidemiology of subjects with mild to moderate chronic renal insufficiency (CRI), defined as reduced glomerular filtration rate (GFR) not requiring renal replacement therapy. This review discusses some of the methodological challenges presented by the epidemiological study of mild to moderate CRI that have not been adequately addressed in the literature. Issues that relate to defining the prevalence of CRI include between-laboratory differences in serum creatinine (SCr) assays, within-person measurement errors in SCr, and differences in SCr in different demographic groups that are independent of GFR. Issues that relate to examining CRI as an outcome include the choice between a "slope" or "threshold" analysis. Issues that relate to examining CRI as an exposure include the choice of renal function measure (for example, SCr vs. estimated GFR) in multivariable analysis, whether to normalize renal function to body surface area or other body size parameters, potential effect modification of the association between CRI and the outcome and the complex relation between CRI, adverse outcomes, potential confounders and intermediary variables. As we enter an era of more intensive study of mild to moderate CRI, recognition of these potential pitfalls should guide researchers toward improving the quality of epidemiological research in this field.

    Title Bone Mineral Density is Not Diminished by Mild to Moderate Chronic Renal Insufficiency.
    Date October 2002
    Journal Kidney International
    Excerpt

    BACKGROUND: Persons with end-stage renal disease are at higher risk for osteopenia and hip fracture relative to the age-matched general population. Persons with mild to moderate chronic renal insufficiency (CRI) may have reduced bone mineral density (BMD) as a result of abnormalities in acid-base and vitamin D-parathyroid hormone homeostasis. METHODS: We analyzed data on 13,848 adults aged 20 and above from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994). Regression models were used to determine the relationship between femoral BMD and renal function, the latter assessed using serum creatinine, blood urea nitrogen or Cockcroft-Gault creatinine clearance. To control for confounding, we fit sex-stratified models that adjusted for age, weight, height, race-ethnicity, menopausal status, estrogen use, activity level, family history of osteoporosis, diuretic use, and dietary intake of calcium and alcohol. RESULTS: Although subjects with reduced renal function had significantly lower femoral BMD in unadjusted analysis, the association between CRI and bone mineral density was extinguished after adjustment in the multivariate models. In fact, controlling for only sex, age and weight was sufficient to extinguish any negative association between decreased renal function and decreased bone mineral density. CONCLUSION: Although subjects with worse renal function have significantly lower femoral BMD, this association can be explained by confounding, principally by sex, age and weight. After taking into account the facts that women, older individuals and smaller individuals have less renal function and lower BMD, renal function itself is not independently associated with BMD.

    Title Refining Predictive Models in Critically Ill Patients with Acute Renal Failure.
    Date October 2002
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Mortality rates in acute renal failure remain extremely high, and risk-adjustment tools are needed for quality improvement initiatives and design (stratification) and analysis of clinical trials. A total of 605 patients with acute renal failure in the intensive care unit during 1989-1995 were evaluated, and demographic, historical, laboratory, and physiologic variables were linked with in-hospital death rates using multivariable logistic regression. Three hundred and fourteen (51.9%) patients died in-hospital. The following variables were significantly associated with in-hospital death: age (odds ratio [OR], 1.02 per yr), male gender (OR, 2.36), respiratory (OR, 2.62), liver (OR, 3.06), and hematologic failure (OR, 3.40), creatinine (OR, 0.71 per mg/dl), blood urea nitrogen (OR, 1.02 per mg/dl), log urine output (OR, 0.64 per log ml/d), and heart rate (OR, 1.01 per beat/min). The area under the receiver operating characteristic curve was 0.83, indicating good model discrimination. The model was superior in all performance metrics to six generic and four acute renal failure-specific predictive models. A disease-specific severity of illness equation was developed using routinely available and specific clinical variables. Cross-validation of the model and additional bedside experience will be needed before it can be effectively applied across centers, particularly in the context of clinical trials.

    Title Association of Renal Insufficiency with Treatment and Outcomes After Myocardial Infarction in Elderly Patients.
    Date October 2002
    Journal Annals of Internal Medicine
    Excerpt

    BACKGROUND: Patients with end-stage renal disease are known to have decreased survival after myocardial infarction, but the association of less severe renal dysfunction with survival after myocardial infarction is unknown. OBJECTIVES: To determine how patients with renal insufficiency are treated during hospitalization for myocardial infarction and to determine the association of renal insufficiency with survival after myocardial infarction. DESIGN: Cohort study. SETTING: All nongovernment hospitals in the United States. PATIENTS: 130 099 elderly patients with myocardial infarction hospitalized between April 1994 and July 1995. MEASUREMENTS: Patients were categorized according to initial serum creatinine level: no renal insufficiency (creatinine level < 1.5 mg/dL [<132 micromol/L]; n = 82 455), mild renal insufficiency (creatinine level, 1.5 to 2.4 mg/dL [132 to 212 micromol/L]; n = 36 756), or moderate renal insufficiency (creatinine level, 2.5 to 3.9 mg/dL [221 to 345 micromol/L]; n = 10 888). Vital status up to 1 year after discharge was obtained from Social Security records. RESULTS: Compared with patients with no renal insufficiency, patients with moderate renal insufficiency were less likely to receive aspirin, beta-blockers, thrombolytic therapy, angiography, and angioplasty during hospitalization. One-year mortality was 24% in patients with no renal insufficiency, 46% in patients with mild renal insufficiency, and 66% in patients with moderate renal insufficiency (P < 0.001). After adjustment for patient and treatment characteristics, mild (hazard ratio, 1.68 [95% CI, 1.63 to 1.73]) and moderate (hazard ratio, 2.35 [CI, 2.26 to 2.45]) renal insufficiency were associated with substantially elevated risk for death during the first month of follow-up. This increased mortality risk continued until 6 months after myocardial infarction. CONCLUSIONS: Renal insufficiency was an independent risk factor for death in elderly patients after myocardial infarction. Targeted interventions may be needed to improve treatment for this high-risk population.

    Title Inflammatory Markers Are Unrelated to Physical Activity, Performance, and Functioning in Hemodialysis.
    Date October 2002
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    OBJECTIVE: To determine the associations among dietary intake and inflammatory cytokines with physical activity, function, and performance in maintenance dialysis patients. DESIGN: Cross-sectional analysis of cohort study. SETTING: University-affiliated dialysis units, general clinical research center. SUBJECTS: Multiethnic cohort of maintenance hemodialysis patients. MAIN OUTCOME MEASURES: Physical activity by accelerometry; physical performance by gait speed, stair climbing, and chair raising; physical functioning by the Medical Outcomes Study Short Form 36-item questionnaire subscale scores; and maximal and adjusted activity scores of human activity profile. RESULTS: Levels of inflammatory cytokines were uniformly high. Tumor necrosis factor-alpha was directly correlated with dietary protein and energy intake; no other cytokines were directly or inversely correlated with intake. Dietary intake was associated with physical activity, as expected, and not significantly associated with performance or function (with the exception of gait speed). There were no significant associations among inflammatory cytokines and physical activity, performance, or function. CONCLUSION: Although dietary intake and inflammation may independently influence traditional proxies of nutritional status, this analysis provides no evidence for a link between cytokines and physical activity, performance, or function in hemodialysis patients. More research is required to understand the role of cytokines in protein energy malnutrition and the mechanisms of wasting and functional decline in the dialysis population.

    Title With Bioimpedance Spectroscopy, the Errors Get Fat when the Patients Get Slim.
    Date August 2002
    Journal Jpen. Journal of Parenteral and Enteral Nutrition
    Title Renal Insufficiency with Monoclonal Gammopathy and Urticarial Vasculitis.
    Date April 2002
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title Cardiac Calcification in Adult Hemodialysis Patients. A Link Between End-stage Renal Disease and Cardiovascular Disease?
    Date March 2002
    Journal Journal of the American College of Cardiology
    Excerpt

    OBJECTIVES: We sought to determine clinical and laboratory correlates of calcification of the coronary arteries (CAs), aorta and mitral and aortic valves in adult subjects with end-stage renal disease (ESRD) receiving hemodialysis. BACKGROUND: Vascular calcification is known to be a risk factor for ischemic heart disease in non-uremic individuals. Patients with ESRD experience accelerated vascular calcification, due at least in part to dysregulation of mineral metabolism. Clinical correlates of the extent of calcification in ESRD have not been identified. Moreover, the clinical relevance of calcification as measured by electron-beam tomography (EBT) has not been determined in the ESRD population. METHODS: We conducted a cross-sectional analysis of 205 maintenance hemodialysis patients who received baseline EBT for evaluation of vascular and valvular calcification. We compared subjects with and without clinical evidence of atherosclerotic vascular disease and determined correlates of the extent of vascular and valvular calcification using multivariable linear regression and proportional odds logistic regression analyses. RESULTS: The median coronary artery calcium score was 595 (interquartile range, 76 to 1,600), values consistent with a high risk of obstructive coronary artery disease in the general population. The CA calcium scores were directly related to the prevalence of myocardial infarction (p < 0.0001) and angina (p < 0.0001), and the aortic calcium scores were directly related to the prevalence of claudication (p = 0.001) and aortic aneurysm (p = 0.02). The extent of coronary calcification was more pronounced with older age, male gender, white race, diabetes, longer dialysis vintage and higher serum concentrations of calcium and phosphorus. Total cholesterol (and high-density lipoprotein and low-density lipoprotein subfractions), triglycerides, hemoglobin and albumin were not significantly related to the extent of CA calcification. Only dialysis vintage was significantly associated with the prevalence of valvular calcification. CONCLUSIONS: Coronary artery calcification is common, severe and significantly associated with ischemic cardiovascular disease in adult ESRD patients. The dysregulation of mineral metabolism in ESRD may influence vascular calcification risk.

    Title "wishing Don't Make It So"--why We Need a Randomized Clinical Trial of High-intensity Hemodialysis.
    Date February 2002
    Journal Journal of the American Society of Nephrology : Jasn
    Title Correlates of Acute Renal Failure in Patients Receiving Parenteral Amphotericin B.
    Date January 2002
    Journal Kidney International
    Excerpt

    BACKGROUND: While parenteral amphotericin B is an effective therapy for serious fungal infections, it frequently causes acute renal failure (ARF). This study identified correlates of ARF in amphotericin B therapy and used them to develop clinical prediction rules. METHODS: All 643 inpatients receiving parenteral amphotericin B therapy at one tertiary care hospital were included. Data regarding correlates were obtained both electronically and from manual chart review in a subsample of 231 patients. ARF was defined as a 50% increase in the baseline creatinine with a peak > or =2.0 mg/dL. RESULTS: Among 643 episodes, ARF developed in 175 (27%). In the larger group, the only independent correlate of ARF was male gender (OR = 2.2, 95% CI, 1.5 to 3.3). In the subsample (N = 231), independent correlates of ARF were maximum daily amphotericin dosage, location at the time of initiation of amphotericin therapy, and concomitant use of cyclosporine. These data were used to develop two clinical prediction rules. A rule using only data available at initiation of therapy stratified patients into groups with probability of ARF ranging from 15 to 54%, while a rule including data available during therapy (maximum daily dose) stratified patients into groups with probability of ARF ranging from 4 to 80%. CONCLUSIONS: Acute renal failure occurred in a quarter of the patients. Correlates of ARF at the beginning and during the course of amphotericin therapy were identified and then combined to allow stratification according to ARF risk. These data also provide evidence for guidelines for the selection of patients for alternative therapies.

    Title Determinants of Physical Performance in Ambulatory Patients on Hemodialysis.
    Date January 2002
    Journal Kidney International
    Excerpt

    BACKGROUND: Physical performance measures, particularly gait speed, have been useful as predictors of loss of independence, institutionalization, and mortality in older nonuremic individuals. Gait speed has not been evaluated as a predictor of these important outcomes in patients on hemodialysis, nor have the determinants of gait speed in the dialysis population been studied. METHODS: We performed a cross-sectional analysis to determine whether demographic, clinical, or nutritional status variables were related to physical performance in a group of 46 hemodialysis patients treated at three University of California San Francisco-affiliated dialysis units. Three physical performance measures were examined, including gait speed, time to climb stairs, and time to rise from a chair five times in succession. Forward stepwise linear-regression analysis was performed with each physical performance measure as the dependent variable and the following candidate predictor variables: age, gender, body mass index, dialysis vintage, Kt/V, albumin, blood urea nitrogen, creatinine, hematocrit, lean body mass, phase angle, ferritin, and the following comorbidities: hypertension, diabetes mellitus, coronary artery disease, peripheral vascular disease, and cerebrovascular disease. RESULTS: Subjects included 31 men and 15 women aged 22 to 87 years (mean +/- SD, 52 +/- 17). The mean gait speed for the group was 113.1 +/- 34.5 cm/s (low compared with norms established for persons of similar age). Results of multivariable regression showed that age, albumin, and Kt/V were important determinants of gait speed in this population. Overall, the model explained 52% of the variability in gait speed (r = 0.72, P < 0.0001). Qualitatively similar results were obtained using stair-climbing time or chair-rising time as the dependent variables, except that comorbidity was more important than age for stair climbing. The addition of physical activity level to the models did not eliminate the associations of albumin or Kt/V with physical performance. CONCLUSIONS: Physical performance is significantly impaired in ambulatory hemodialysis patients and is related to age, serum albumin, and dialysis dose. Prospective studies are needed to determine whether modification of dialysis dose or nutritional interventions can improve physical performance in patients on hemodialysis.

    Title Guided Medication Dosing for Inpatients with Renal Insufficiency.
    Date December 2001
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Usual drug-prescribing practices may not consider the effects of renal insufficiency on the disposition of certain drugs. Decision aids may help optimize prescribing behavior and reduce medical error. OBJECTIVE: To determine if a system application for adjusting drug dose and frequency in patients with renal insufficiency, when merged with a computerized order entry system, improves drug prescribing and patient outcomes. DESIGN, SETTING, AND PATIENTS: Four consecutive 2-month intervals consisting of control (usual computerized order entry) alternating with intervention (computerized order entry plus decision support system), conducted in September 1997-April 1998 with outcomes assessed among a consecutive sample of 17 828 adults admitted to an urban tertiary care teaching hospital. INTERVENTION: Real-time computerized decision support system for prescribing drugs in patients with renal insufficiency. During intervention periods, the adjusted dose list, default dose amount, and default frequency were displayed to the order-entry user and a notation was provided that adjustments had been made based on renal insufficiency. During control periods, these recommended adjustments were not revealed to the order-entry user, and the unadjusted parameters were displayed. MAIN OUTCOME MEASURES: Rates of appropriate prescription by dose and frequency, length of stay, hospital and pharmacy costs, and changes in renal function, compared among patients with renal insufficiency who were hospitalized during the intervention vs control periods. RESULTS: A total of 7490 patients were found to have some degree of renal insufficiency. In this group, 97 151 orders were written on renally cleared or nephrotoxic medications, of which 14 440 (15%) had at least 1 dosing parameter modified by the computer based on renal function. The fraction of prescriptions deemed appropriate during the intervention vs control periods by dose was 67% vs 54% (P<.001) and by frequency was 59% vs 35% (P<.001). Mean (SD) length of stay was 4.3 (4.5) days vs 4.5 (4.8) days in the intervention vs control periods, respectively (P =.009). There were no significant differences in estimated hospital and pharmacy costs or in the proportion of patients who experienced a decline in renal function during hospitalization. CONCLUSIONS: Guided medication dosing for inpatients with renal insufficiency appears to result in improved dose and frequency choices. This intervention demonstrates a way in which computer-based decision support systems can improve care.

    Title Inflammation and Dietary Protein Intake Exert Competing Effects on Serum Albumin and Creatinine in Hemodialysis Patients.
    Date August 2001
    Journal Kidney International
    Excerpt

    BACKGROUND: Cross-sectional studies have shown an inverse correlation between serum C-reactive protein (CRP) and serum albumin concentration in hemodialysis patients. The net effects of inflammation and dietary protein intake on nutritional markers over time are unknown. METHODS: To explore the effects of CRP and normalized protein catabolic rate (nPCR) on serum albumin and creatinine, we analyzed six consecutive months of laboratory data from 364 hemodialysis patients, using a multivariable Mixed model with conservative biases. RESULTS: The overall trend over time in serum albumin was slightly positive (0.039 g/dL/month) and in serum creatinine slightly negative (-0.052 mg/dL/month). With increasing CRP, serum albumin declined significantly (-0.124 g/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes, and nPCR, P < 0.0001). Serum albumin increased with increasing nPCR (0.021 g/dL/month per 0.1 g/kg/day, P < 0.0001). The effect of CRP on albumin was attenuated in African Americans and at a higher nPCR. Corresponding values for creatinine mirrored those for albumin. With increasing CRP, creatinine declined significantly [-0.142 mg/dL/month per unit increase in log CRP, adjusted for age, gender, race, diabetes (time since initiation of dialysis; vintage), Kt/V, and nPCR, P = 0.002]. Serum creatinine increased with increasing nPCR (0.183 mg/dL/month per g/kg/day, P < 0.0001). CONCLUSIONS: Proxies of inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. These data provide a rationale for prospective testing of dietary protein supplementation in hemodialysis patients with biochemical evidence of ongoing inflammation and "malnutrition."

    Title Cardiac Arrest and Sudden Death in Dialysis Units.
    Date August 2001
    Journal Kidney International
    Excerpt

    BACKGROUND: For patients with end-stage renal disease and their providers, dialysis unit-based cardiac arrest is the most feared complication of hemodialysis. However, relatively little is known regarding its frequency or epidemiology, or whether a fraction of these events could be prevented. METHODS: To explore clinical correlates of dialysis unit-based cardiac arrest, 400 reported arrests over a nine-month period from October 1998 through June 1999 were reviewed in detail. Clinical characteristics of patients who suffered cardiac arrest were compared with a nationally representative cohort of> 77,000 hemodialysis patients dialyzed at Fresenius Medical Care North America-affiliated facilities. RESULTS: The cardiac arrest rate was 400 out of 5,744,708, corresponding to a rate of 7 per 100,000 hemodialysis sessions. Cardiac arrest was more frequent during Monday dialysis sessions than on other days of the week. Case patients were nearly twice as likely to have been dialyzed against a 0 or 1.0 mEq/L potassium dialysate on the day of cardiac arrest (17.1 vs. 8.8%). Patients who suffered a cardiac arrest were on average older (66.3 +/- 12.9 vs. 60.2 +/- 15.4 years), more likely to have diabetes (61.8 vs. 46.8%), and more likely to use a catheter for vascular access (34.1 vs. 27.8%) than the general hemodialysis population. Sixteen percent of patients experienced a drop in systolic pressure of 30 mm Hg or more prior to the arrest. Thirty-seven percent of patients who suffered cardiac arrest had been hospitalized within the past 30 days. Sixty percent of patients died within 48 hours of the arrest, including 13% while in the dialysis unit. CONCLUSIONS: Cardiac arrest is a relatively infrequent but devastating complication of hemodialysis. To reduce the risk of adverse cardiac events on hemodialysis, the dialysate prescription should be evaluated and modified on an ongoing basis, especially following hospitalization in high-risk patients.

    Title Mortality and Costs of Acute Renal Failure Associated with Amphotericin B Therapy.
    Date August 2001
    Journal Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
    Excerpt

    To assess the mortality and resource utilization that results from acute renal failure associated with amphotericin B therapy, 707 adult admissions in which parenteral amphotericin B therapy was given were studied at a tertiary-care hospital. Main outcome measures were mortality, length of stay, and costs; we controlled for potential confounders, including age, sex, insurance status, baseline creatinine level, length of stay before beginning amphotericin B therapy, and severity of illness. Among 707 admissions, there were 212 episodes (30%) of acute renal failure. When renal failure developed, the mortality rate was much higher: 54% versus 16% (adjusted odds of death, 6.6). When acute renal failure occurred, the mean adjusted increase in length of stay was 8.2 days, and the adjusted total cost was $29,823. Although residual confounding exists despite adjustment, the increases in resource utilization that we found are large and the associated mortality is high when acute renal failure occurs following amphotericin B therapy.

    Title Beta(2)-microglobulin Modified with Advanced Glycation End Products Delays Monocyte Apoptosis.
    Date July 2001
    Journal Kidney International
    Excerpt

    BACKGROUND: A local inflammatory reaction to beta(2)-microglobulin (beta(2)m) amyloid deposits by monocytes/macrophages is a characteristic histologic feature of dialysis-related amyloidosis (DRA). Since beta(2)m modified with advanced glycation end products (AGE-beta(2)m) is a major constituent of amyloid in DRA, we tested the hypothesis that AGE-beta(2)m affects apoptosis and phenotype of human monocytes. METHODS: Human peripheral blood monocytes were incubated with or without in vitro-derived AGE-beta(2)m, and their viability, extent of apoptosis, morphology, and function examined over the subsequent four days. RESULTS: AGE-modified but not unmodified beta(2)m significantly delayed spontaneous apoptosis of human peripheral blood monocytes in adherent and nonadherent cultures. The effect of AGE-beta(2)m on monocytes apoptosis was time- and dose-dependent and was attenuated by a blocking antibody directed against the human AGE receptor (RAGE). There was no difference in effect between AGE-beta(2)m and that of AGE-modified human serum albumin. Culture of monocytes with AGE-beta(2)m did not alter membrane expression of Fas or Fas ligand. Monocytes cultured with AGE-beta(2)m underwent substantial changes in morphology similar to those observed when monocytes differentiate into macrophages. The cultured cells increased in size and vacuolization, and their content of beta-glucuronidase and acid phosphatase increased by 5- to 10-fold at day 4. Expression of the monocyte--macrophage membrane antigens HLA-DR, CD11b, and CD11c also increased at day 4. Although exhibiting phenotypic characteristics of macrophages, monocytes cultured with AGE-beta(2)m functioned differently than macrophages cultured with serum. Superoxide production in response to phorbol myristic acetate was maintained in monocytes cultured with AGE-beta(2)m, but declined with time in cells cultured with serum. Constitutive synthesis of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and prostaglandin E2 (PGE2) increased in monocytes cultured for four to six days with AGE-beta(2)m. CONCLUSIONS: These findings support a novel role for AGE-modified proteins such as AGE-beta(2)m that may contribute to the development of a local inflammatory response, with predominant accumulation of monocytes/macrophages, in DRA.

    Title Validation of Questionnaires to Estimate Physical Activity and Functioning in End-stage Renal Disease.
    Date July 2001
    Journal Kidney International
    Excerpt

    BACKGROUND: Patients on dialysis are less physically active than sedentary persons with normal kidney function. To assess the consequences of inactivity and the results of efforts to increase activity in the end-stage renal disease (ESRD) population, valid instruments to measure physical activity and physical functioning in this group are needed. METHODS: We performed a cross-sectional study to establish the validity in ESRD of several questionnaires designed to measure physical activity or physical functioning in the general population. Questionnaires studied included the Stanford 7-day Physical Activity Recall questionnaire (PAR), the Physical Activity Scale for the Elderly (PASE), the Human Activity Profile (HAP), and the Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Physical activity was measured using three-dimensional activity monitors (accelerometers) over a seven-day period (the "gold standard"). Patients also underwent physical performance tests, including measurement of gait speed, stair climbing time, and chair rising time. Study questionnaires were administered, and questionnaire results were compared with each other and with activity monitor and physical performance test results. RESULTS: Thirty-nine maintenance hemodialysis patients participated in the study. Dialysis patients scored worse than previously published healthy norms on all tests. All questionnaires correlated with seven-day accelerometry and with at least one measure of physical performance. The HAP correlated best with accelerometry (r = 0.78, P < 0.0001). Seventy-five percent of the variability in physical activity measured by accelerometry could be explained by a model that combined information from the HAP and the PASE. The HAP and the physical functioning scale of the SF-36 were about equally well correlated with physical performance measures. CONCLUSIONS: These questionnaires are valid in patients on hemodialysis and should be used to study the physical activity and rehabilitation efforts in this population further.

    Title Hyperparathyroidism and Dialysis Vintage.
    Date June 2001
    Journal Clinical Nephrology
    Excerpt

    BACKGROUND: Secondary hyperparathyroidism and its effects on bone and viscera are among the most important complications of end-stage renal disease. Despite its ubiquity, little is known about the treated natural history of the disorder. METHODS: We assembled a cohort of 310 patients with endstage renal disease on hemodialysis who were participants in one of four clinical trials of the phosphate binder sevelamer. Baseline parathyroid hormone levels were collected, and the relation between dialysis vintage and other clinical variables with parathyroid hormone were described. RESULTS: There was a direct relation between dialysis vintage and the severity of hyperparathyroidism. Other variables that were significantly associated with PTH on univariate analysis included age, African American race, Kt/V, and the serum concentrations of calcium, phosphate, and bicarbonate. Multivariable linear regression analysis yielded three significant predictors of PTH: calcium, phosphorus, and vintage (5.8% (4.0-7.5%) expected increase in PTH per year of vintage). The model R2 was 0.22. CONCLUSION: Dialysis vintage is a key determinant of the severity of secondary hyperparathyroidism. Vintage and certain laboratory variables should be considered in the evaluation of therapies aimed at modifying the treated natural history of this disorder.

    Title Suspected Iron Dextran-related Adverse Drug Events in Hemodialysis Patients.
    Date May 2001
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.

    Title Mechanisms Underlying Renoprotection During Renin-angiotensin System Blockade.
    Date March 2001
    Journal American Journal of Physiology. Renal Physiology
    Excerpt

    Potential determinants of chronic renal disease (CRD) progression were studied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated with candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurgery. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 +/- 9; Ena = 148 +/- 8 mmHg), urinary protein excretion rates (U(pr)V) increased over 24 wk (Csn = 92 +/- 10; Ena = 99 +/- 8mg/day). Glomerulosclerosis scores (GS) at 24 wk were similar for Csn (42 +/- 7%) vs. Ena (42 +/- 4%), values close to those of untreated controls at 12 wk (43 +/- 4%). At 24 wk, SBP and UprV correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-beta1 and monocyte chemoattractant protein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF-beta1, MCP-1, and interleukin-1beta and renal injury at 24 wk. Cns and Ena are thus equally effective renoprotective agents in this model. During renin-angiotensin system inhibition, renoprotection is dependent on control of both SBP and UprV. Incomplete suppression of renal cytokine gene expression may also contribute to CRD progression.

    Title Crystalloids Versus Colloids for Resuscitation in Shock.
    Date February 2001
    Journal Current Opinion in Nephrology and Hypertension
    Excerpt

    The optimal composition of fluid for volume resuscitation in critically ill patients has been the subject of controversy for decades. Clinicians are faced with several options, including crystalloid solutions of varying tonicity, several colloid preparations (albumin and others), and blood products. Some of these solutions may be differentially distributed between the intra- and extravascular, and intra- and extracellular compartments, accounting for a variety of physiological effects. Two recently published meta-analyses concluded that colloids afford no survival benefit in critically ill patients compared with crystalloids. Albumin infusion may be of more value in patients with cirrhosis, or in those at high risk of acute renal failure. Additional randomized trials will be needed to establish the optimal composition and volume of colloid or crystalloid solutions for resuscitation in shock.

    Title Prealbumin is As Important As Albumin in the Nutritional Assessment of Hemodialysis Patients.
    Date January 2001
    Journal Kidney International
    Excerpt

    BACKGROUND: Although serum prealbumin is considered a valid indicator of nutritional status in hemodialysis patients, there is relatively little evidence that its determination is of major prognostic significance. In this study, we aimed to determine the independent association of serum prealbumin with survival in hemodialysis patients, after adjusting for serum albumin and other indicators of protein energy nutritional status. METHODS: Serum prealbumin was measured in more than 1600 maintenance hemodialysis patients. We determined the correlations among prealbumin and other indicators of nutritional status, including serum albumin, and bioimpedance-derived indicators of body composition. The relationship between serum prealbumin and survival was determined using proportional hazards regression. RESULTS: The serum albumin was directly correlated with the serum prealbumin (r = 0.47, P < 0.0001), but still explained <25% of the variability in prealbumin. Prealbumin was inversely related to mortality, with a relative risk reduction of 6% per 1 mg/dL increase in prealbumin, even after adjusting for case mix, serum albumin, and other nutritional indicators. The increase in risk with lower serum prealbumin concentrations was observed whether the serum albumin was high or low. CONCLUSION: In hemodialysis patients, the serum prealbumin provides prognostic value independent of the serum albumin and other established predictors of mortality in this population.

    Title Sevelamer with and Without Calcium and Vitamin D: Observations from a Long-term Open-label Clinical Trial.
    Date December 2000
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    OBJECTIVE: To determine the effects of sevelamer hydrochloride on serum phosphorus, calcium, calcium x phosphate product, and parathyroid hormone (PTH) in patients treated with and without vitamin D metabolites and calcium supplementation. DESIGN: Long-term, open-label clinical trial. SETTING: Hemodialysis units. PATIENTS: One hundred ninety-two adult patients with end-stage renal disease on hemodialysis. INTERVENTION: An extended treatment period of sevelamer hydrochloride, preceded and followed by phosphate binder washout periods. MAIN OUTCOME MEASURES: Treatment-related changes in serum phosphorus, calcium, calcium x phosphate product, and PTH. RESULTS: Subjects treated with sevelamer alone, sevelamer with vitamin D metabolites (with or without calcium), and sevelamer with calcium without vitamin D experienced significant reductions in mean serum phosphorus (range, 2.1 to -2.9 mg/dL) and the calcium x phosphate product (range, -16.3 to -23.4 mg2/dL2). The mean serum calcium concentration increased in all subgroups except those treated with sevelamer alone (range, +0.3 to +0.5 mg/dL). In contrast, only subjects treated concurrently with vitamin D metabolites experienced a reduction in PTH. Subjects treated with sevelamer alone or sevelamer with calcium without vitamin D experienced an increase in PTH with treatment. CONCLUSION: Sevelamer hydrochloride is a safe and effective phosphate binder in hemodialysis patients. Sevelamer should be used in combination with vitamin D metabolites to jointly control hyperphosphatemia and hyperparathyroidism. Randomized clinical trials will be required to determine the optimal management strategies for metabolic bone disease in end-stage renal disease, as well as less advanced stages of chronic renal insufficiency.

    Title Atrial Natriuretic Factor in Oliguric Acute Renal Failure. Anaritide Acute Renal Failure Study Group.
    Date October 2000
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 microgram/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P = 0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P = 0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P = 0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality.

    Title Chronic Renal Confusion: Insufficiency, Failure, Dysfunction, or Disease.
    Date August 2000
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    The terms routinely used to describe states of reduced glomerular filtration rate (GFR) not requiring renal replacement therapy are poorly defined. With increasing interest in the epidemiology of chronic renal insufficiency and the timing of initiation of dialysis, terms such as "pre-ESRD" and "pre-dialysis" have been popularized, again without clear definition. Unambiguous terminology should be adopted. The authors favor using the term chronic renal insufficiency to describe states of reduced GFR not severe enough to require dialysis or transplantation. The authors propose classifying patients with GFR of 60 to 41 mL/min, 40 to 21 mL/min, and 20 mL/min or below as having mild, moderate, and advanced degrees of chronic renal insufficiency, respectively. The use of this terminology will facilitate communication among nephrologists and other physicians and provide a framework for comparison of populations across cohort studies and clinical trials.

    Title Physical Activity Levels in Patients on Hemodialysis and Healthy Sedentary Controls.
    Date August 2000
    Journal Kidney International
    Excerpt

    BACKGROUND: Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients. METHODS: Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire. RESULTS: Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02). CONCLUSIONS: Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.

    Title Predicting Acute Renal Failure After Coronary Bypass Surgery: Cross-validation of Two Risk-stratification Algorithms.
    Date August 2000
    Journal Kidney International
    Excerpt

    BACKGROUND: Acute renal failure (ARF) requiring dialysis after coronary artery bypass grafting (CABG) occurs in 1 to 5% of patients and is independently associated with postoperative mortality, even after case-mix adjustment. A risk-stratification algorithm that could reliably identify patients at increased risk of ARF could help improve outcomes. METHODS: To assess the validity and generalizability of a previously published preoperative renal risk-stratification algorithm, we analyzed data from the Quality Measurement and Management Initiative (QMMI)1 patient cohort. The QMMI includes all adult patients (N = 9498) who underwent CABG at 1 of 12 academic tertiary care hospitals from August 1993 to October 1995. ARF requiring dialysis was the outcome of interest. Cross-validation of a recursive partitioning algorithm developed from the VA Continuous Improvement in Cardiac Surgery Program (CICSP) was performed on the QMMI. An additive severity score derived from logistic regression was also cross-validated on the QMMI. RESULTS: The CICSP recursive partitioning algorithm discriminated well (ARF vs. no ARF) in QMMI patients, even though the QMMI cohort was more diverse. Rates of ARF were similar among risk subgroups in the CICSP tree, as was the overall ranking of subgroups by risk. Using logistic regression, independent predictors of ARF in the QMMI cohort were similar to those found in the CICSP. The CICSP additive severity score performed well in the QMMI cohort, successfully stratifying patients into low-, medium-, high-, and very high-risk groups. CONCLUSIONS: The CICSP preoperative renal-risk algorithms are valid and generalizable across diverse populations.

    Title Leveling the "paying" Field in End-stage Renal Disease.
    Date July 2000
    Journal The American Journal of Medicine
    Title Survival After Acute Myocardial Infarction in Patients with End-stage Renal Disease: Results from the Cooperative Cardiovascular Project.
    Date June 2000
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Cardiovascular disease (CVD) is the most common cause of death in patients with end-stage renal disease (ESRD). The optimal management strategy in this population is unknown. We studied 640 patients with ESRD and acute myocardial infarction during 1994 to 1995 as part of the Health Care Financing Administration's Cooperative Cardiovascular Project. The majority of patients were treated with medical therapy alone, 46 patients (7%) were treated with percutaneous transluminal coronary angioplasty (PTCA), and 29 patients (5%) underwent coronary artery bypass grafting (CABG). Patient characteristics and comorbid conditions were similar among the three groups. The overall 1-year mortality rate was 53%. Advanced age, low or high body mass index, history of peripheral vascular disease or stroke, the inability to walk independently, and several indicators of cardiac dysfunction were associated with an increased relative risk (RR) for death. Survival curves differed significantly by treatment modality, with 1-year survival rates of 45%, 54%, and 69% in the medical therapy alone, PTCA, and CABG groups, respectively (P = 0.03). After adjustment for confounding variables, the RR for death was less (but not significantly so) in the CABG group (RR, 0.6; 95% confidence interval, 0.3 to 1.1). There are no randomized clinical trial data to guide therapy of CVD in patients with ESRD. On the basis of these and other available data, CABG may be the optimal therapy for CVD in ESRD. In light of the exceptionally poor outcomes observed for patients treated with medical therapy alone, it may be premature to dismiss PTCA as a therapeutic option in this population.

    Title Ochrobactrum Anthropi Bacteremia in a Patient on Hemodialysis.
    Date June 2000
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Although newer tunneled dialysis catheters offer improved capacity for blood flow and efficiency of dialysis, catheter-associated bacteremia remains an extremely important complication of this access strategy. This is a report of a case of catheter-associated bacteremia with Ochrobactrum anthropi, a water-borne gram-negative rod with an unusual pattern of antibiotic resistance. Given the organism's hydrophilic property and the frequency of catheter use in debilitated individuals with end-stage renal disease, Ochrobactrum anthropi infection should be considered in the differential diagnosis of a hemodialysis patient with unexplained fever.

    Title Vintage, Nutritional Status, and Survival in Hemodialysis Patients.
    Date May 2000
    Journal Kidney International
    Excerpt

    BACKGROUND: The link between dialysis "vintage" (length of time on dialysis in months to years) and survival has been difficult to define, largely because of selection effects. End-stage renal disease (ESRD) is thought to be a wasting illness, but there are no published reports describing the associations between vintage and body composition in hemodialysis patients. METHODS: We explored the relationships among vintage, nutritional status, and survival in a 3009 patient cohort of prevalent hemodialysis patients. Body weight, total body water, body cell mass, and phase angle by bioelectrical impedance analysis were the body composition parameters of interest. We examined vintage as an explanatory variable in multiple linear regression analyses (adjusted for age, gender, race, and diabetes) using body composition parameters and biochemical indicators of nutritional status as dependent variables. Proportional hazards regression was used to evaluate the association of vintage and survival with and without adjustment for case mix and laboratory variables. RESULTS: Dialysis vintage was 3.8 +/- 3.7 (median 2.6) years. Body composition parameters tended to be lower after dialysis year 2. Linear estimates per year of vintage beyond year 2 include -0.66 kg body wt (P < 0.0001), -0.17 kg total body water (P = 0.0003), -0.14 kg body cell mass (P < 0.0001), and -0.07 degrees phase angle (P < 0.0001). In unadjusted analyses, vintage was not associated with survival, either as a linear or higher order term. The adjustment for case mix yielded a vintage term associated with an increased relative risk (RR) of death (RR 1.04 (95% CI, 1.01 to 1.07 per year). A further adjustment for laboratory data yielded a RR of 1.06 (95% CI, 1.03 to 1.09 per year). CONCLUSION: Dialysis vintage is related to nutritional status in hemodialysis patients, with vintage of more than years associated with a significant decline in all measured nutritional parameters. Cross-sectional analyses probably underestimate these effects. A year accrued on dialysis is associated with a 6% increase in the risk of death, all else equal. Longitudinal assessments of nutritional status, including body composition, are required to better understand the natural history of wasting with ESRD and its implications for long-term survival.

    Title Issues in Renal Nutrition for Persons from the Former Soviet Union.
    Date May 2000
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Excerpt

    Dietary practices differ greatly among individuals by race and ethnicity. The importance of these differences is accentuated in patients with end-stage renal disease, a population for whom dietary restrictions are often prescribed. In addition to the known variation in dietary practices among US-born whites and African-Americans, persons of other ethnicities often present new and unique challenges to the dialysis-nutrition care team. The UCSF-Mt. Zion Dialysis Unit (San Francisco, CA) is a university-affiliated dialysis unit that serves an ethnically diverse population in San Francisco's Western Addition neighborhood. Ten percent to 15% of patients are recent immigrants from the former Soviet Union. This report highlights the dietary practices of this immigrant community and the need for ethnicity-specific renal nutrition recommendations in modern dialysis practice.

    Title Acute Renal Failure with Interstitial Nephritis in a Patient with Aids.
    Date March 2000
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title Renal Nutrition in the New Millennium.
    Date February 2000
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Title Long-term Effects of Sevelamer Hydrochloride on the Calcium X Phosphate Product and Lipid Profile of Haemodialysis Patients.
    Date December 1999
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    BACKGROUND: Short-term studies have suggested that sevelamer hydrochloride, a non-aluminium- and non-calcium-containing hydrogel, is an effective phosphate binder in haemodialysis patients, and may produce favourable changes in the lipid profile. METHODS: To determine the long-term effectiveness of sevelamer hydrochloride, we performed an open-label clinical trial in 192 adult patients with end-stage renal disease on haemodialysis. Drug-related changes in the concentrations of serum phosphorus, calcium, calcium x phosphate product, parathyroid hormone, and low- and high-density lipoprotein cholesterol concentrations were the major outcomes of interest. RESULTS: Treatment with sevelamer was associated with a mean change in serum phosphorus of -0.71+/-0.77 mmol/l, serum calcium of 0. 08+/-0.22 mmol/l, and calcium x phosphate product of -1.46+/-1.78 mmol/l (P<0.0001 for all comparisons). There were no significant overall treatment-related changes in parathyroid hormone. Serum levels of LDL cholesterol decreased by 0.81+/-0.75 mmol/l (mean -30%, P<0.0001) and HDL cholesterol increased by a mean of 0.15+/-0.29 mmol/l (mean +18%, P<0.0001). Drug-related adverse events were infrequent and most were of mild intensity. CONCLUSION: Sevelamer is a safe and effective phosphate binder that leads to significant improvements in the calcium x phosphate product and lipid profile of haemodialysis patients.

    Title Exploring the Reverse J-shaped Curve Between Urea Reduction Ratio and Mortality.
    Date December 1999
    Journal Kidney International
    Excerpt

    BACKGROUND: Although accepted worldwide as valid measures of dialysis adequacy, neither the Kt/V (urea clearance determined by kinetic modeling) nor the urea reduction ratio (URR) have unambiguously predicted survival in hemodialysis patients. Because the ratio Kt/V can be high with either high Kt (clearance x time) or low V (urea volume of distribution) and V may be a proxy for skeletal muscle mass and nutritional health, we hypothesized that the increase in the relative risk of death observed among individuals dialyzed in the top 10 to 20% of URR or Kt/V values might reflect a competing risk of malnutrition. METHODS: A total of 3,009 patients who underwent bioelectrical impedance analysis were stratified into quintiles of URR. Laboratory indicators of nutritional status and two bioimpedance-derived parameters, phase angle and estimated total body water, were compared across quintiles. The relationship between dialysis dose and mortality was explored, with a focus on how V influenced the structure of the dose-mortality relationship. RESULTS: There were statistically significant differences in all nutritional parameters across quintiles of URR or Kt/V, indicating that patients in the fifth quintile (mean URR, 74.4 +/- 3.1%) were more severely malnourished on average than patients in all or some of the other quintiles. The relationship between URR and mortality was decidedly curvilinear, resembling a reverse J shape that was confirmed by statistical analysis. An adjustment for the influence of V on URR or Kt/V was performed by evaluating the Kt-mortality relationship. There was no evidence of an increase in the relative risk of death among patients treated with high Kt. Higher Kt was associated with a better nutritional status. CONCLUSION: We conclude that the increase in mortality observed among those patients whose URR or Kt/V are among the top 10 to 20% of patients reflects a deleterious effect of malnutrition (manifest by a reduced V) that overcomes whatever benefit might be derived from an associated increase in urea clearance. Identification of patients who achieve extremely high URR (>75%) or single-pooled Kt/V (>1.6) values using standard dialysis prescriptions should prompt a careful assessment of nutritional status. Confounding by protein-calorie malnutrition may limit the utility of URR or Kt/V as a population-based measure of dialysis dose.

    Title Bioelectrical Impedance Methods in Clinical Research: a Follow-up to the Nih Technology Assessment Conference.
    Date December 1999
    Journal Nutrition (burbank, Los Angeles County, Calif.)
    Excerpt

    In 1994, the National Institutes of Health (NIH) convened a Technology Assessment Conference "to provide physicians with a responsible assessment of bioelectrical impedance analysis (BIA) technology for body composition measurement." In 1997, Serono Symposia USA, Inc., organized an invited panel of scientists and clinicians, with extensive research and clinical experience with BIA, to provide an update. Panel members presented reviews based on their own work and published studies for the intervening years. Updates were provided on the single and multifrequency BIA methods and models; continued clinical research experiences; efforts toward establishing population reference norms; and the feasibility of establishing guidelines for potential diagnostic use of BIA in a clinical setting. This report provides a summary of the panel's findings including a consensus on several technical and clinical issues related to the research use of BIA, and those areas that are still in need of additional study.

    Title The Urea [clearance X Dialysis Time] Product (kt) As an Outcome-based Measure of Hemodialysis Dose.
    Date August 1999
    Journal Kidney International
    Excerpt

    BACKGROUND: The normalized treatment ratio [Kt/V = the ratio of the urea clearance x time product to total body water] and the urea reduction ratio (URR) have become widely accepted measures of dialysis dose. Both are related to and derived from pharmacokinetic models of blood urea concentration during the dialysis cycle. Theoretical reconsideration of the models revealed that the premise about V on which they rest (that is, that V is a passive diluent with no survival-associated properties of its own) is flawed if the intended use of the models is for profiling clinical outcome (for example, mortality) rather than estimating urea concentration. As a proxy for body mass, V has survival-associated properties of its own. Thus, indexing clearance x time to body size could create an offsetting combination whereby one measure favorably associated with survival (Kt) is divided by another (for example, V). Observed clinical paradoxes support that interpretation. For example, patients with a low body mass have both higher URR and higher mortality than heavier patients. Increasing mortality is often observed at high URR, suggesting the possibility of "over-dialysis." Black patients tend to be treated at lower URR than whites but enjoy better survival on dialysis. Therefore, clearance x time was evaluated as an outcome-based measure of dialysis dose, not indexed to V, and various body size estimates were evaluated as separate and distinct measures. METHODS: The retrospective sample included 17,141 black and white hemodialysis patients treated three times per week. Logistic regression analysis was used to evaluate death odds in age-, gender-, race-, and diabetes-adjusted models. Kt and five body size estimates (total body water or V, body weight, body weight adjusted for height, body surface area, and body mass index) were evaluated using two analytical strategies. First, all of the measures were treated as continuous variables to explore different statistical models. Second, Kt and the body size measures were divided into groups to construct risk profiles. RESULTS: All evaluations revealed improving death odds with increasing Kt (whether adjusted for the body size estimates or not) and also with increasing body size (whether adjusted for Kt or not) for each estimate of size. Significant statistical interactions of Kt with gender, but not Kt with race, were observed in all models. There were no statistical interactions, suggesting that higher Kt was routinely required with increasing body size. Separate risk profiles for males and females suggested a higher Kt threshold for males. CONCLUSIONS: The urea clearance x time is a valid outcome-based measure of dialysis dose and is not confounded by indexing it to an estimate of body size, which has outcome-associated properties of its own. Dialysis prescriptions for males and females should be regarded separately, but there appears no need to make a distinction between the races.

    Title Aggravated Renal Dysfunction During Intensive Therapy for Advanced Chronic Heart Failure.
    Date August 1999
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown. METHODS: We reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of >/=2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients. RESULTS: ARD, defined as >/=25% increase in serum creatinine concentration to >/=2 mg/dL, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 +/- 16 years vs 51 +/- 13 years; P =.006) and had lower baseline creatinine clearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min; P =.01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70% vs 29%, P =.02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P =.002). CONCLUSIONS: In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes.

    Title Estimates of Body Composition As Intermediate Outcome Variables: Are Dexa and Bia Ready for Prime Time?
    Date August 1999
    Journal Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation
    Title Evidence-based Organ Allocation.
    Date July 1999
    Journal The American Journal of Medicine
    Excerpt

    BACKGROUND: There are not enough cadaveric kidneys to meet the demands of transplant candidates. The equity and efficiency of alternative organ allocation strategies have not been rigorously compared. METHODS: We developed a five-compartment Monte Carlo simulation model to compare alternative organ allocation strategies, accommodating dynamic changes in recipient and donor characteristics, patient and graft survival rates, and quality of life. The model simulated the operations of a single organ procurement organization and attempted to predict the evolution of the transplant waiting list for 10 years. Four allocation strategies were compared: a first-come first-transplanted system; a point system currently utilized by the United Network of Organ Sharing; an efficiency-based algorithm that incorporated correlates of patient and graft survival; and a distributive efficiency algorithm, which had an additional goal of promoting equitable allocation among African-American and other candidates. RESULTS: A 10-year computer simulation was performed. The distributive efficiency policy was associated with a 3.5%+/-0.8% (mean +/- SD) increase in quality-adjusted life expectancy (33.9 months vs 32.7 months), a decrease in the median waiting time to transplantation among those who were transplanted (6.6 months vs 16.3 months), and an increase in the overall likelihood of transplantation (61% vs 45%), compared with the United Network of Organ Sharing algorithm. Improved equity and efficiency were also seen by race (African-American vs other), sex, and age (<50 or > or =50 years). Sensitivity analyses did not appreciably change the qualitative results. CONCLUSION: Evidence-based organ allocation strategies in cadaveric kidney transplantation would yield improved equity and efficiency measures compared with existing algorithms.

    Title Metabolic and Monetary Costs of Avoidable Parenteral Nutrition Use.
    Date April 1999
    Journal Jpen. Journal of Parenteral and Enteral Nutrition
    Excerpt

    BACKGROUND: We prospectively collected data on in patients receiving parenteral nutrition to determine the magnitude of potentially preventable metabolic and monetary costs associated with parenteral nutrition. METHODS: Parenteral nutrition was prescribed by the treating physicians with optional consultation from a multidisciplinary metabolic support service. Days on parenteral nutrition, appropriateness of parenteral nutrition, metabolic complications, and avoidable parenteral nutrition charges were determined. Parenteral nutrition use was considered "indicated" or "not indicated" based on the American Society for Parenteral and Enteral Nutrition guidelines and "preventable" if the gastrointestinal tract was functional but not accessed when possible. RESULTS: Of the 209 parenteral nutrition starts, 62% were indicated, 23% were preventable, and 15% were not indicated. Parenteral nutrition starts were deemed indicated in 82% of instances in which a metabolic support service consult was obtained, compared with 56% in which a consultation was not obtained (p = .004). Hyperglycemia was the most common metabolic complication, with an overall incidence of 20%. Metabolic complications occurred less frequently in patients who received a metabolic support service consultation compared with patients who did not (34% vs 66% of parenteral nutrition days, respectively; p = .004). Parenteral nutrition use of < or =5 days duration was significantly less frequent among patients who received metabolic support service consultation (16% vs 35%; p = .002). Parenteral nutrition that was not indicated or preventable resulted in excess annualized patient charges of more than one half million dollars not accounting for charges related to treatment of potentially avoidable parenteral nutrition complications. CONCLUSIONS: This study illustrates that not-indicated and preventable parenteral nutrition initiation, short-term parenteral nutrition use, and metabolic complications are less likely when patients receive consultation by a multidisciplinary team with expertise in nutrition and metabolic support. Furthermore, the avoidance of inappropriate parenteral nutrition use translates into substantial cost savings.

    Title A Randomized Trial of Sevelamer Hydrochloride (renagel) with and Without Supplemental Calcium. Strategies for the Control of Hyperphosphatemia and Hyperparathyroidism in Hemodialysis Patients.
    Date April 1999
    Journal Clinical Nephrology
    Excerpt

    OBJECTIVE: We have previously shown sevelamer hydrochloride (RenaGel) to be an effective and well-tolerated treatment for hyperphosphatemia in hemodialysis patients. PATIENTS AND METHODS: We performed a randomized clinical trial to compare the efficacy of RenaGel alone and RenaGel with calcium, using the serum phosphorus concentration and intact parathyroid hormone (PTH) as the principal outcomes of interest. Calcium (900 mg elemental) was provided as a once-nightly dose on an empty stomach. 71 patients were randomized and included in the intent-to-treat population; 55 completed the 16-week study period (2 weeks washout, 12 weeks treatment, 2 weeks washout). 49% of subjects were taking vitamin D metabolites. RESULTS: Serum phosphorus and PTH rose significantly when patients stopped their phosphate binders during both washout periods. RenaGel and RenaGel with calcium were equally effective at reducing serum phosphorus (mean change -2.4 mg/dL vs. -2.3 mg/dL). RenaGel with calcium was associated with a small increase in serum calcium (mean change 0.3 mg/dL vs. 0.0 mg/dL in RenaGel group, P = 0.09) that was not statistically significant. During the treatment phase, the reduction in PTH tended to be greater in the RenaGel with calcium group (median change -67.0 vs. -22.5 pg/mL in RenaGel group, P = 0.07). Non-users of vitamin D metabolites treated with RenaGel with calcium experienced a significant decrease in PTH (median change -114.5 vs. -22 pg/mL in RenaGel group, P = 0.006). Adverse events were seen with equal frequency in both groups, being generally mild in intensity, and rarely attributable to the drugs. CONCLUSION: We conclude that RenaGel and RenaGel with calcium are similarly effective in the treatment of ESRD-related hyperphosphatemia. Provision of supplemental calcium or metabolites of vitamin D with RenaGel may enhance control of hyperparathyroidism.

    Title Modality-specific Nutrition Support in Esrd: Weighing the Evidence.
    Date February 1999
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Protein-calorie malnutrition affects a large fraction of patients with end-stage renal disease (ESRD) and contributes significantly to the high rates of mortality and morbidity observed in this population. Observational studies of specific interventions, including intradialytic parenteral nutrition (IDPN), suggest that aggressive nutrition support may be of some benefit to some patients with ESRD. Due in part to lack of data derived from prospective, randomized clinical trials, and to the large expense associated with these therapies, Medicare and other payers have strongly discouraged the prescription of IDPN and other intermittent, dialysis-specific methods of nutrition support, such as intraperitoneal nutrition (IPN). The "burden of proof" has been placed on the dialysis community. In response, we must continue to emphasize the importance of securing nutritional health for all patients on or anticipating renal replacement therapy. Intradialytic parenteral nutrition should be reserved for patients who are taking in sufficient calories yet are unable to tolerate oral or enteral protein-rich foods or formulas designed to meet daily protein requirements (> or = 1.5 g/kg in some patients). Intradialytic parenteral nutrition should not be prescribed in place of total parenteral nutrition (TPN) if the latter is truly needed. Creative methods of nutrition support, including the use of dietary supplements at dialysis (intradialytic oral or enteral nutrition), should be explored. Prospective clinical trials investigating the effects of nutrition support on survival, hospitalization rates, health-related quality of life, and functional status, are urgently needed.

    Title Cancer Screening and Detection in Patients with End-stage Renal Disease.
    Date January 1999
    Journal The International Journal of Artificial Organs
    Title Effects of Estrogen Replacement Therapy on the Lipoprotein Profile in Postmenopausal Women with Esrd.
    Date December 1998
    Journal Kidney International
    Excerpt

    BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.

    Title Dose of Hemodialysis and Survival: Differences by Race and Sex.
    Date December 1998
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Although blacks receive lower doses of hemodialysis than whites, their survival when receiving dialysis treatment is better than that for whites. Previous studies of the relationship between the dose of dialysis and patient survival have not controlled for differences in patient characteristics. OBJECTIVE: To examine the association of mortality with the dose of hemodialysis for clusters of patients categorized by race and sex. DESIGN: Retrospective analysis of laboratory data and mortality outcomes from 1994, using a national database of hemodialysis patients. PATIENTS: A total of 18144 black and white patients receiving hemodialysis 3 times weekly who either lived the entire year receiving hemodialysis or died. MAIN OUTCOME MEASURES: The fractional reduction of urea in a single dialysis session as the measured hemodialysis dose (urea reduction ratio [URR]) after controlling for race, sex, age, and diabetes mellitus. Mortality was determined by strata of URRs and albumin and creatinine levels. RESULTS: Across all age categories, blacks had lower URRs than whites, and men had lower URRs than women. In an age-adjusted model for evaluating interactions among URRs, race, sex, and diabetes, the association of URR with mortality risk was weak among blacks, particularly black men. After adjustment for age and diabetes, death probability curves were most steep for white women with URR values less than 60%. The death probability curves were least steep for black men. There was no meaningful difference between death probability and albumin or creatinine concentration among the race by sex clusters. CONCLUSION: Using URR, the usual measure of hemodialysis dose, the assumption that the association between dialysis dose and survival is uniform across demographic groups appears incorrect. Comparisons of the quality of dialysis patient care should not rely on URR alone to predict patient survival.

    Title Clearance of Pneumocystis Carinii Cysts in Acute P Carinii Pneumonia: Assessment by Serial Sputum Induction.
    Date December 1998
    Journal Chest
    Excerpt

    STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP. DESIGN: Prospective cohort evaluation. SETTING: University medical center. PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP. MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year. RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse. CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.

    Title Haemobilia Mimicking Acute Cholecystitis Following Percutaneous Renal Biopsy.
    Date November 1998
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Title Beta 2-microglobulin Modified with Advanced Glycation End Products Modulates Collagen Synthesis by Human Fibroblasts.
    Date June 1998
    Journal Kidney International
    Excerpt

    Beta 2-microglobulin amyloidosis (A beta 2m) is a serious complication for patients undergoing long-term dialysis. beta 2-microglobulin modified with advanced glycation end products (beta 2m-AGE) is a major component of the amyloid in A beta 2m. It is not completely understood whether beta 2m-AGE plays an active role in the pathogenesis of A beta 2m, or if its presence is a secondary event of the disease. beta 2-microglobulin amyloid is mainly located in tendon and osteo-articular structures that are rich in collagen, and local fibroblasts constitute the principal cell population in the synthesis and metabolism of collagen. Recent identification of AGE binding proteins on human fibroblasts lead to the hypothesis that the fibroblast may be a target for the biological action of beta 2m-AGE. The present study demonstrated that two human fibroblast cell lines exhibited a decrease in procollagen type I mRNA and type I collagen synthesis after exposure to beta 2m-AGE for 72 hours. Similar results were observed using AGE-modified albumin. Antibody against the RAGE, the receptor for AGE, attenuated this decrease in synthesis, indicating that the response was partially mediated by RAGE. In addition, antibody against epidermal growth factor (EGF) attenuated the decrease in type I procollagen mRNA and type I collagen induced by beta 2m-AGE, suggesting that EGF acts as an intermediate factor. These findings support the hypothesis that beta 2m-AGE actively participates in connective tissue and bone remodeling via a pathway involving fibroblast RAGE, and at least one interposed mediator, the growth factor EGF.

    Title Predictors of Mortality and the Provision of Dialysis in Patients with Acute Tubular Necrosis. The Auriculin Anaritide Acute Renal Failure Study Group.
    Date June 1998
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.

    Title Independent Association Between Acute Renal Failure and Mortality Following Cardiac Surgery.
    Date May 1998
    Journal The American Journal of Medicine
    Excerpt

    PURPOSE: To determine whether there is an independent association of acute renal failure requiring dialysis with operative mortality after cardiac surgery. PATIENTS AND METHODS: The 42,773 patients who underwent coronary artery bypass or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality, with and without adjustment for comorbidity and postoperative complications. Crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from logistic regression analysis. RESULTS: Acute renal failure occurred in 460 (1.1%) patients. Overall operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. The unadjusted OR for death was 39 (95% CI 32 to 48). After adjustment for comorbid factors related to the development of acute renal failure (surgery type, baseline renal function, preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status, peripheral vascular disease, pulmonary rales, left ventricular ejection fraction below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and the cross-product of systolic blood pressure and surgery type), the OR was 27 (95% CI 22 to 34). Further adjustment was made for seven postoperative complications (low cardiac output, cardiac arrest, perioperative myocardial infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat cardiopulmonary bypass, stroke or coma, and mediastinitis), that were independently associated with operative mortality. The OR adjusted for comorbidity and postoperative complications associated with acute renal failure was 7.9 (95% CI 6 to 10). CONCLUSIONS: Acute renal failure was independently associated with early mortality following cardiac surgery, even after adjustment for comorbidity and postoperative complications. Interventions to prevent or improve treatment of this condition are urgently needed.

    Title Olecranon Bursitis Caused by Infection with Candida Lusitaniae.
    Date May 1998
    Journal The Journal of Rheumatology
    Excerpt

    We describe a 59-year-old woman with diabetes and chronic asthma treated with prednisone and methotrexate who developed chronic olecranon bursitis caused by Candida lusitaniae. Infection, especially with unusual microbial pathogens, should be considered in cases of chronic bursitis in patients taking immunosuppressive medicine, even if the classic signs of septic bursitis are absent. Infection with C. lusitaniae, a component of the normal mycoflora, may be a marker of serious immunosuppression, as this patient ultimately died of a Pneumocystis carinii infection.

    Title Aminoguanidine Inhibits Advanced Glycation End Products Formation on Beta2-microglobulin.
    Date April 1998
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Because advanced glycation end products (AGE)-modified beta2-microglobulin (AGE-beta2M) is a dominant constituent of amyloid in dialysis-related amyloidosis (DRA), AGE-beta2M may be directly involved in the pathobiology of DRA. In experimental diabetes mellitus, blocking the formation of AGE prevents AGE-mediated tissue damage. In this study, it is postulated that similar pharmacologic intervention may be beneficial in DRA. Aminoguanidine, a nucleophilic hydrazine compound that prevents AGE formation on collagen, may have a similar effect on the advanced glycation of beta2M. To test this hypothesis, beta2M was incubated in vitro with 50 or 100 mM D-glucose for 3 wk in the presence and absence of incremental concentrations of aminoguanidine. On the basis of enzyme-linked immunosorbent assay and immunoblots using anti-AGE-keyhole limpet hemocyanin antibody, aminoguanidine inhibited glucose-induced N(epsilon)-(carboxymethyl)lysine formation on beta2M. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, 26 to 53% inhibition occurred. Fluorospectrometry examination showed that aminoguanidine also inhibited the formation of fluorescent AGE on beta2M in a dose-dependent manner. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, fluorescent product generation was inhibited by 30 to 70%. Furthermore, aminoguanidine suppressed the AGE formation on beta2M bound to AGE-modified collagen. If aminoguanidine is similarly active in vivo, this compound may be of clinical utility for treating DRA in patients on maintenance dialysis.

    Title Dialysis: Cost-effective "support" for Patients with Acute Renal Failure.
    Date March 1998
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Title Antigen-independent Determinants of Graft Survival in Living-related Kidney Transplantation.
    Date February 1998
    Journal Kidney International. Supplement
    Excerpt

    We used the United Network of Organ Sharing database to define the antigen independent risk factors which contributed to the survival of 8,582 kidney transplants performed in the U.S. between October 1987 and December 1991, using multivariable regression techniques. In this analysis, death with a functioning graft was censored. The risk ratio for graft loss was high when recipients were African-American or had high body surface area, or when donors were older or female. The analysis shows that antigen independent factors that are associated with lower donor kidney mass or increased recipient size play a significant role in living donor kidney transplant loss, as they do in cadaver kidney transplantation.

    Title Bioimpedance Norms for the Hemodialysis Population.
    Date January 1998
    Journal Kidney International
    Excerpt

    More than 3,000 hemodialysis patients were examined with single-frequency bioelectrical impedance analysis (BIA). Distributions of resistance, reactance, phase angle (PA), and estimates of total body water (TBW) and body cell mass (BCM) by BIA were determined, and compared with traditional laboratory markers of nutritional status. Bioimpedance parameters and body composition estimates differed significantly by age, sex, race, and diabetic status. PA and BCM correlated directly with serum creatinine, albumin, and prealbumin concentrations. Population-based norms for bioimpedance parameters and estimates of body composition are provided.

    Title On the Design and Analysis of Multicenter Trials in Acute Renal Failure.
    Date December 1997
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Improving outcomes for patients with acute renal failure (ARF) is one of the most urgent tasks for 21st century nephrologists and other critical care physicians. The incidence of hospital-acquired ARF is rising (to 5% or more), partly because of changes in the demographic and clinical characteristics of the hospitalized patient population. When ARF is severe enough to require dialysis, in-hospital mortality rates are distressingly high, in excess of 50% in most published studies. In the past several years, a number of attempts have been made to influence the course of ARF, either relatively early (eg, atrial natriuretic peptide [ANP], insulin growth factor-1 [IGF-1]) or coincident with the dialysis procedure in severe cases (eg, variations in dialysis membrane and modality). Several lessons can be learned from these efforts. This article will briefly address issues in the design and analysis of clinical trials, focusing on elements of special interest to practitioners of renal medicine.

    Title The Rise and Fall of Atrial Natriuretic Peptide for Acute Renal Failure.
    Date November 1997
    Journal Current Opinion in Nephrology and Hypertension
    Excerpt

    Atrial natriuretic peptide can increase glomerular filtration rate and filtration fraction and can promote natriuresis, effects that would logically seem to improve renal function after acute tubular necrosis from ischemic or toxic injury. Early human trials suggested a beneficial effect of atrial natriuretic peptide on creatinine clearance, and a reduction in the need for dialysis in treated patients. However, randomized, placebo-controlled trials have failed to show a clinically relevant benefit on survival, dialysis-free survival, or renal function in patients treated with this agent.

    Title Renal Vasculitis with Hiv Seropositivity: Potential Manifestation of Cytomegalovirus Infection.
    Date September 1997
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    The associations among human immunodeficiency virus (HIV) infection, focal segmental glomerulosclerosis, and its variant, "collapsing glomerulopathy," often leading to chronic renal failure, are well described. HIV-seropositive patients may also develop a variety of immune complex-mediated glomerular diseases, including postinfectious glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis. Herein we describe a case of pauci-immune necrotizing renal vasculitis in an HIV-seropositive patient, thereby expanding the differential diagnosis of acute renal failure in this setting.

    Title Interaction Between Beta 2-microglobulin and Advanced Glycation End Products in the Development of Dialysis Related-amyloidosis.
    Date July 1997
    Journal Kidney International
    Excerpt

    Dialysis related amyloidosis (DRA) is a progressive debilitating complication of long-term dialysis. beta 2-microglobulin (beta 2m) amyloid deposition occurs preferentially in older patients and initially is located in collagen-rich osteo-articular tissues. Since an age-dependent increase in the formation of advanced glycation end products (AGE) has been observed in collagen-containing structures, we hypothesized that AGE-modified beta 2m in the amyloid of DRA may be formed locally in osteo-articular structures as a subsequent event of its binding to collagen-AGE. Based on this hypothesis, we investigated the binding between beta 2m and AGE-modified collagen (collagen-AGE) in vitro. Significantly larger amounts of human beta 2m were bound to types I to IV of immobilized collagen-AGE than to unmodified collagens (P < 0.0001). The quantity of beta 2m bound to collagen-AGE was dependent on the concentrations of both beta 2m and of AGE contained in collagen (P < 0.01). Unmodified beta 2m was more avidly bound to collagen-AGE or collagen in comparison to AGE-modified beta 2m (P < 0.0001). beta 2m bound to collagen-AGE could be modified further by nonenzymatic glycosylation during three weeks of incubation with physiologic concentrations of glucose. Similar processes in vivo may be important in the pathobiology of DRA.

    Title Development of a Population-specific Regression Equation to Estimate Total Body Water in Hemodialysis Patients.
    Date July 1997
    Journal Kidney International
    Excerpt

    We have previously shown that the impedance index (height corrected resistance) is a valid and reliable correlate of total body water (TBW) in hemodialysis patients. We estimated TBW by single frequency bioelectrical impedance analysis (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW equation from routinely available demographic and anthropometric variables. The mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American, and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/- 9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit on a two-thirds random sample, deriving significant parameter estimates for the variables age, gender, height, weight, diabetic status, weight squared, and the cross-products of age and gender, age and weight, gender and weight, and height and weight. The equation was then validated in the remaining one-third sample, and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/- 7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of 3.5 and 2.6 kg, respectively. A population-specific equation provides superior prediction of TBW in hemodialysis patients. The use of formulae developed and validated in non-uremic populations may result in underestimates of TBW in patients with ESRD, and potentially, overestimates of dialysis dose approximated by the clearance-time to TBW ratio (Kt/V).

    Title Nephrology.
    Date June 1997
    Journal Jama : the Journal of the American Medical Association
    Title A Practical Approach to Acute Renal Failure.
    Date June 1997
    Journal The Medical Clinics of North America
    Excerpt

    Acute renal failure represents a wide variety of renal diseases, which may be challenging to diagnose and even more challenging to treat. As understanding of these diseases improves, so perhaps will clinicians' ability to treat them.

    Title Poorer Graft Survival in African-american Transplant Recipients Cannot Be Explained by Hla Mismatching.
    Date April 1997
    Journal Advances in Renal Replacement Therapy
    Excerpt

    African-American kidney-transplant recipients have exhibited a higher rate of graft failure than whites and other patient groups. Many have attributed this discrepancy to disparities in HLA matching against a predominantly white donor pool. We compared the relative risks of cadaveric and living-related graft failure in African-American, white, Hispanic, and Asian transplant recipients, adjusting for a variety of demographic and clinical covariates. The relative risks of graft failure were increased by 44% and 73% in African-American recipients of cadaveric and living-related organs, respectively. Although Asians were subject to a comparable degree of HLA mismatching, cadaveric graft survival in Asian recipients was superior to that in whites. These results suggest that other variables not captured by registry data account for the increase in graft failure observed in African-Americans. More focused investigation into the causes and prevention of graft failure in African-Americans is required.

    Title Preoperative Renal Risk Stratification.
    Date April 1997
    Journal Circulation
    Excerpt

    BACKGROUND: After cardiac surgery, acute renal failure (ARF) requiring dialysis develops in 1% to 5% of patients and is strongly associated with perioperative morbidity and mortality. Prior studies have attempted to identify predictors of ARF but have had insufficient power to perform multivariable analyses or to develop risk stratification algorithms. METHODS AND RESULTS: We conducted a prospective cohort study of 43 642 patients who underwent coronary artery bypass or valvular heart surgery in 43 Department of Veterans Affairs medical centers between April 1987 and March 1994. Logistic regression analysis was used to identify independent predictors of ARF requiring dialysis. A risk stratification algorithm derived from recursive partitioning was constructed and was validated on an independent sample of 3795 patients operated on between April and December 1994. The overall risk of ARF requiring dialysis was 1.1%. Thirty-day mortality in patients with ARF was 63.7%, compared with 4.3% in patients without ARF. Ten clinical variables related to baseline cardiovascular disease and renal function were independently associated with the risk of ARF. A risk stratification algorithm partitioned patients into low-risk (0.4%), medium-risk (0.9% to 2.8%), and high-risk (> or = 5.0%) groups on the basis of several of these factors and their interactions. CONCLUSIONS: The risk of ARF after cardiac surgery can be accurately quantified on the basis of readily available preoperative data. These findings may be used by physicians and surgeons to provide patients with improved risk estimates and to target high-risk subgroups for interventions aimed at reducing the risk and ameliorating the consequences of this serious complication.

    Title Performance Characteristics of a Dialysis-related Amyloidosis Questionnaire.
    Date March 1997
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    To evaluate the effects of beta-2 microglobulin amyloidosis on functional status, a 19-item self-administered questionnaire exploring two major domains-symptoms and disability-was developed as part of this study. Fifteen patients with dialysis-related amyloidosis (DRA) were identified and compared with 15 age-matched control subjects who had been on hemodialysis for less than 24 months. Demographic data, Charlson comorbidity scores, and other clinical and laboratory variables were recorded. Total dialysis-related amyloidosis questionnaire (DRAQ) score (52.1 +/- 16.3 versus 24.4 +/- 6.2, P < 0.0001) and the scores of the symptom (24.5 +/- 7.0 versus 11.5 +/- 2.3, P < 0.0001) and disability (27.5 +/- 10.8 versus 12.9 +/- 4.0, P < 0.0001) subscales were markedly increased among patients with DRA. Baseline characteristics among case and control subjects were similar, except for serum creatinine concentration, which tended to be lower among patients with DRA (8.9 +/- 2.6 versus 11.5 +/- 2.3 mg/dL, P = 0.07). Instrument reliability and internal consistency were high. With a total DRAQ score of 30 or more, the sensitivity and specificity of the instrument were 93% and 80%, respectively. The DRAQ is a reliable, internally consistent, and valid instrument that may be suitable for population screening and clinical practice.

    Title Poly[allylamine Hydrochloride] (renagel): a Noncalcemic Phosphate Binder for the Treatment of Hyperphosphatemia in Chronic Renal Failure.
    Date February 1997
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade. Although relatively well-tolerated, a large fraction of patients treated with calcium develop hypercalcemia, particularly when administered concurrently with calcitriol, despite a lowering of the dialysate calcium concentration. We evaluated the efficacy of cross-linked poly[allylamine hydrochloride] (RenaGel; Geltex Pharmaceuticals, Waltham, MA), a nonabsorbable calcium- and aluminum-free phosphate binder, in a randomized, placebo-controlled, double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period. RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder. The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel (6.6 +/- 2.1 mg/dL to 5.4 +/- 1.5 mg/dL) compared with placebo (7.0 +/- 2.1 mg/dL to 7.2 +/- 2.4 mg/dL; P = 0.037). There was no significant change in serum calcium concentration in either treatment group. The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients (P = 0.013 and P = 0.003, respectively) without a concomitant reduction in high-density lipoprotein cholesterol (P = 0.93). There was no difference among recipients of RenaGel and placebo in terms of adverse events. RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease.

    Title Trimethoprim-sulfamethoxazole and Hypouricemia.
    Date January 1997
    Journal Clinical Nephrology
    Excerpt

    BACKGROUND: Hypouricemia has been reported in a substantial fraction of patients with AIDS and attributed to an HIV-related renal urate transport defect. We tested the alternative hypothesis that hypouricemia was associated with the administration of high-dose trimethoprim-sulfamethoxazole (TMP-SMX). METHODS: Sociodemographic, clinical, and repeated laboratory data on 45 hospitalized patients with Pneumocystis carinii pneumonia (PCP) with and without HIV infection, were abstracted by a blinded reviewer. The primary outcome of interest was the percent change in serum uric acid concentration from baseline to hospital day 5 +/- 1. RESULTS: Subjects who received TMP-SMX were older (mean age 44.8 vs. 37.0, p = 0.02), less likely to be HIV-seropositive (61% vs. 94%, p = 0.01), and more likely to have received glucocorticoid therapy (75% vs. 35%, p = 0.01) than those who received pentamidine, dapsone-trimethoprim, clindamycin-primaquine, sulfadiazine-pyramethamine, or a combination of these agents. The administration of TMP-SMX was associated with a 37% +/- 12% reduction in serum uric acid concentration, adjusting for the effects of age, sex, race, HIV antibody status, renal function, serum sodium, and the use of diuretics and glucocorticoids (p = 0.005). CONCLUSION: Among a diverse cohort of hospitalized patients with PCP, treatment with high-dose TMP-SMX was strongly associated with a reduction in serum uric acid concentration over time.

    Title Antigen-independent Determinants of Cadaveric Kidney Transplant Failure.
    Date December 1996
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    OBJECTIVE: To determine the association of various antigen-independent factors with long-term cadaveric kidney transplant failure. DESIGN: Cohort analytic study. SETTING: Kidney transplant centers (N=131) in the United States. PATIENTS: A total of 31 515 patients who received cadaveric kidney transplants between October 1987 and December 1991. Patients with unknown or uninterpretable vital status or graft survival time (n=264 [0.8%]) were excluded. MAIN OUTCOME MEASURE: Graft failure, estimated at 2 extremes, depending on whether the death of a patient with a functioning graft was censored ("censored graft failure") or not ("uncensored graft failure"). RESULTS: During the 62-month study period, 5883 patients required the reinstitution of dialysis because of graft failure, 2404 patients died with graft failure, and 2041 patients died with a functioning graft. The relative risks of censored and uncensored graft failure were significantly associated with donor age, sex, and race and recipient body surface area, after adjusting for recipient age, sex, race, diabetes, cold ischemia time, panel cross-reactivity, pretransplant blood transfusions, previous renal transplantation, functional status, and HLA antigen mismatch. CONCLUSIONS: In cadaveric kidney transplantation, selected demographic and anthropometric factors are significantly related to long-term graft outcomes, even after adjusting for well-known antigen-dependent risk factors. These results support the hypothesis that the supply of viable donor nephrons and the physiologic demands of the transplant recipient are important determinants of long-term graft failure. Antigen-independent factors such as donor age should be incorporated into organ allocation algorithms to optimize equity and efficiency.

    Title Birth Weight and Adult Hypertension and Obesity in Women.
    Date December 1996
    Journal Circulation
    Excerpt

    BACKGROUND: Low birth weight has been associated with an increased risk of hypertension, and high birth weight has been associated with increased adult body mass index. Published studies on adults have included only a small number of women. METHODS AND RESULTS: We studied 71 100 women in the Nurses Health Study I (NHS I) who were 30 to 55 years of age in 1976 and 92 940 women in the Nurses' Health Study II (NHS II) who were 25 to 42 years of age in 1989. Information on birth weight, blood pressure, physician-diagnosed hypertension, and other relevant variables was collected by biennial mailed questionnaire. Ninety-five percent of the women were white. Compared with women in the middle category of birth weight (NHS I, 7.1 to 8.5 lb; NHS II, 7.0 to 8.4 lb), the age-adjusted odds ratio of hypertension in NHS I women with birth weights < 5.0 lb was 1.39 (95% CI, 1.29 to 1.50); in NHS II, for birth weights < 5.5 lb, the age-adjusted odds ratio was 1.43 (95% CI, 1.31 to 1.56). There was no material change in the estimates after adjustment for other risk factors. In addition, compared with women in NHS I who weighed 7.1 to 8.5 lb at birth, those who weighed > 10 lb had an age-adjusted odds ratio of 1.62 (95% CI, 1.38 to 1.90) of being in the highest (> 29.2 kg/m2) versus the lowest (< 21.9 kg/ m2) quintile of body mass index in midlife. Similar results were seen in the NHS II cohort. CONCLUSIONS: Early life exposures affecting birth weight may be important in the development of hypertension and obesity in adults.

    Title Fanconi's Syndrome and Tubulointerstitial Nephritis in Association with L-lysine Ingestion.
    Date November 1996
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    We report a case of a 44-year-old woman who developed Fanconi's syndrome in association with the oral ingestion of L-lysine. L-lysine is widely available in health food stores and has been recommended in the lay press for the treatment and prevention of recurrent herpes simplex. The development of a severe tubulointerstitial nephritis, and eventual progression to chronic renal failure, underscores the importance of this entity, heretofore unrecognized in humans.

    Title Grafts Vs Fistulas for Hemodialysis Patients: Equal Access for All?
    Date November 1996
    Journal Jama : the Journal of the American Medical Association
    Title Restless Legs Syndrome in End-stage Renal Disease.
    Date October 1996
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    The aim of this study was to evaluate the prevalence of restless legs syndrome (RLS) in patients with end-stage renal disease (ESRD), and to determine its association with sleep disorders and premature discontinuation of dialysis ("sign-offs"). End-stage renal disease patients (N = 204) and a control group of patients with heart disease (N = 129) completed a self-administered questionnaire regarding symptoms of RLS, sleep habits, pruritus, and adherence to dialysis therapy. Laboratory measures and sensory nerve amplitudes were collected on the ESRD patients. Twenty percent of the ESRD patients and 6% of the cardiac patients reported moderate to severe RLS symptomatology. Sleep onset was delayed and total sleep time was diminished in ESRD patients compared with cardiac patients. Symptoms of RLS were directly correlated with all sleep measures as well as with pruritus. Symptoms of RLS, sleep onset latency, and transferrin saturation were independently associated with premature discontinuation of dialysis. Significantly increased risk for mortality was observed in patients with RLS at the 2.5-year follow-up. Restless legs syndrome is a common finding in patients with ESRD and is associated with substantial morbidity.

    Title Is the Administration of Dopamine Associated with Adverse or Favorable Outcomes in Acute Renal Failure? Auriculin Anaritide Acute Renal Failure Study Group.
    Date August 1996
    Journal The American Journal of Medicine
    Excerpt

    PURPOSE: To explore the relationship between the administration of low-dose dopamine and outcomes in acute renal failure. PATIENTS: Two hundred and fifty-six patients with acute renal failure randomized to the placebo arm of a multicenter intervention trial were examined. Independent correlates of low-dose (arbitrarily defined as < 3 micrograms/kg/min) and high-dose (arbitrarily defined as > or = 3 micrograms/kg/min) dopamine administration were identified. The relative risks of death, and the combined outcome of death or dialysis, were estimated using proportional hazards regression with and without adjustment for potential confounding and bias. RESULTS: There were 93 (36%) deaths documented; an additional 52 (20%) patients who survived required dialysis during the 60-day study period. The relative risk (RR) of death associated with the administration of low-dose dopamine was 1.11 (95% confidence interval [95% Cl] 0.66 to 1.89). The RR of death was modestly but not significantly reduced, after adjustment for the probability of treatment assignment and for relevant covariates (RR 0.82, 95% Cl 0.42 to 1.60). The RR of death or dialysis associated with the administration of low-dose dopamine was 1.10 (95% Cl 0.71 to 1.71). The RR of death or dialysis was attenuated by adjustment, but not significantly (RR 0.95, 95% Cl 0.58 to 1.58). CONCLUSION: There is insufficient evidence that the administration of low-dose dopamine improves survival or obviates the need for dialysis in persons with acute renal failure. The routine use of low-dose dopamine should be discouraged until a prospective, randomized, placebo-controlled trial establishes its safety and efficacy.

    Title Non-immunologic Predictors of Chronic Renal Allograft Failure: Data from the United Network of Organ Sharing.
    Date March 1996
    Journal Kidney International. Supplement
    Excerpt

    Experimental evidence and clinical experience suggest that non-immunologic factors are important predictors of long-term renal allograft survival. It has been suggested that chronic allograft failure may in some cases by mediated by non-immunologic factors implicated in the pathobiology of other forms of progressive renal disease. Donor age, sex, and race may influence the "dose" of nephrons delivered in cadaveric renal transplantation. The United Network of Organ Sharing 1994 Public Use Data Tape was used to evaluate these and other risk factors in more than 31,000 recipients of cadaver allografts followed between 1987 and 1992. Female sex and African American race of the donor were important predictors of allograft failure. There was a markedly increased risk of allograft failure at both extremes of donor age. Recipients of large body size had accelerated graft loss. Stratified analyses suggested an interaction between donor and recipient race; nevertheless, all non-immunologic factors examined expressed independent associations with allograft survival. In sum, antigen-independent factors appear to be important determinants of allograft performance. Additional multivariable analyses are required to assess the relative importance of these factors compared with other known immunologic factors, such as HLA antigen mismatch. These findings may have important biomedical and health care policy implications.

    Title Multifrequency Bioelectrical Impedance Estimates the Distribution of Body Water.
    Date March 1996
    Journal Journal of Applied Physiology (bethesda, Md. : 1985)
    Excerpt

    Multifrequency bioelectrical impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water in subjects with end-stage renal disease. The body's resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index (height2/resistance) determined at low frequency (5 kHz) correlated most closely with ECW (r = 0.886) using sodium bromide dilution as the standard of comparison. In contrast, the ratio of height squared to resistance determined at high frequency (500 kHz) correlated most closely with total body water (r = 0.974) using deuterium oxide dilution as the standard of comparison. The ratio of resistance at 500 kHz to resistance at 5 kHz was directly correlated (r = 0.767) with the ratio of ECW to total body water. Multifrequency bioelectrical impedance analysis may assist in the evaluation of body water distribution in endstage renal disease and other clinical disorders of fluid volume and/or distribution.

    Title Nutritional Assessment with Bioelectrical Impedance Analysis in Maintenance Hemodialysis Patients.
    Date December 1995
    Journal Journal of the American Society of Nephrology : Jasn
    Excerpt

    Protein energy malnutrition is common among persons with ESRD and contributes substantially to morbidity and mortality. The usual methods of nutritional assessment, such as anthropometry, can be misleading because of altered tissue hydration. Bioelectrical impedance analysis (BIA) has been recommended by some as a practical nutritional assessment tool but has not been validated in patients with ESRD. Thirty-three stable patients on maintenance hemodialysis were evaluated in an ambulatory clinical research center with simultaneous BIA, dual-energy x-ray absorptiometry, and deuterium oxide (D2O) and sodium bromide (NaBr) isotope dilution studies. Standard determinations of total body water (TBW) and body cell mass (BCM) were obtained and compared with values estimated by BIA. Two separate outpatient BIA measurements were also obtained approximately 2 wk before and after the clinical research center evaluation. BCM estimated by BIA was directly correlated (r = 0.92, P < 0.0001) with BCM determined by DEXA and NaBr. TBW estimated by BIA was directly correlated (r = 0.96, P < 0.0001) with TBW determined by deuterium oxide dilution. The reactance to resistance ratio (Xc/R) derived from BIA was inversely correlated (r = -0.73, P < 0.0001) with the extracellular water/TBW ratio determined by NaBr/D2O. Bland-Altman analyses showed that for TBW, BIA was in excellent agreement with D2O dilution. BCM was modestly underestimated by BIA compared with the dual-energy x-ray absorptiometry/NaBr standard and was adjusted by linear regression. The coefficients of variation on repeated BIA measurements were below 4%, demonstrating test-retest reliability. BIA is a valid and reliable method of nutritional assessment in maintenance hemodialysis patients.

    Title Potential Identifiability and Preventability of Adverse Events Using Information Systems.
    Date March 1995
    Journal Journal of the American Medical Informatics Association : Jamia
    Excerpt

    STUDY OBJECTIVE: To evaluate the potential ability of computerized information systems (ISs) to identify and prevent adverse events in medical patients. DESIGN: Clinical descriptions of all 133 adverse events identified through chart review for a cohort of 3,138 medical patients were evaluated by two reviewers. MEASUREMENTS: For each adverse event, three hierarchical levels of IS sophistication were considered: Level 1--demographics, results for all diagnostic tests, and current medications would be available on-line; Level 2--all orders would be entered on-line by physicians; and Level 3--additional clinical data, such as automated problem lists, would be available on-line. Potential for event identification and potential for event prevention were scored by each reviewer according to two distinct sets of event monitors. RESULTS: Of all the adverse events, 53% were judged identifiable using Level 1 information, 58% were judged identifiable using Level 2 information, and 89% were judged identifiable using Level 3 information. The highest-yield event monitors for identifying adverse events were "panic" laboratory results, unexpected transfer to an intensive care unit, and hospital-incurred trauma. With information from Levels 1, 2, and 3, 5%, 13%, and 23% of the adverse events, respectively, were judged preventable. For preventing these adverse events, guided-dose algorithms, drug-laboratory checks, and drug-patient characteristic checks held the most potential.

    Title The Association of Intradialytic Parenteral Nutrition Administration with Survival in Hemodialysis Patients.
    Date January 1995
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Hemodialysis patients who had received intradialytic parenteral nutrition (IDPN) during 1991 were identified. These patients were compared with unexposed controls after adjusting for demographic variables, baseline renal diagnosis, diabetic status, serum albumin (ALB), creatinine (CRE), and urea reduction ratio. At lower levels of ALB (< or = 3.4 g/dL), treatment with IDPN was associated with a reduction in the odds of death at 1 year, an effect that became stronger at lower levels of CRE (< or = 8.0 mg/dL). In contrast, treatment with IDPN in patients with normal ALB was associated with increased mortality. Time trend analyses of ALB and CRE demonstrated progressive increases toward pretreatment levels in IDPN recipients that were not evident in control subjects. These time trend data suggest that in undernourished hemodialysis patients, IDPN can effect the serum levels of valid biochemical surrogates of visceral and somatic protein nutrition. Albeit retrospective, the improvement in survival at year's end among patients with ALB < or = 3.4 g/dL suggests that malnutrition and its attendant ill effects in hemodialysis patients may respond to aggressive therapeutic intervention, such as IDPN. These important findings should be prospectively confirmed in a randomized clinical trial.

    Title Congenital Oligonephropathy: an Inborn Cause of Adult Hypertension and Progressive Renal Injury?
    Date October 1994
    Journal Current Opinion in Nephrology and Hypertension
    Title Congenital Oligonephropathy and the Etiology of Adult Hypertension and Progressive Renal Injury.
    Date March 1994
    Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
    Excerpt

    Based on the associations reviewed in this report, we have hypothesized that retardation of renal development as occurs in individuals of low birth weight gives rise to increased postnatal risks for systemic and glomerular hypertension as well as enhanced risk of expression of renal disease. This hypothesis draws on observations suggesting (1) a direct relationship between birth weight and nephron number, (2) an inverse relationship between birth weight and later-life hypertension, and (3) an inverse relationship between nephron number and blood pressure, irrespective of whether nephron number is reduced congenitally or in postnatal life (as from partial renal ablation or acquired renal disease). Additional clinical and epidemiologic studies are needed to assess these initial impressions.

    Title Parapharyngeal Soft-tissue Infection with Aeromonas Hydrophila.
    Date April 1992
    Journal Head & Neck
    Excerpt

    Parapharyngeal soft tissue infections may be rapidly progressive and life-threatening. Prompt institution of appropriate antimicrobial therapy is of paramount importance. This report highlights the potential virulence of Aeromonas hydrophila in infection of the head and neck and the need to consider this organism in selected patients.

    Title Saccharomyces Cerevisiae Empyema in a Patient with Esophago-pleural Fistula Complicating Variceal Sclerotherapy.
    Date July 1991
    Journal Chest
    Title Bioprosthetic Tricuspid Valve Stenosis Associated with Extensive Plaque Deposition in Carcinoid Heart Disease.
    Date June 1991
    Journal American Heart Journal
    Title Long-term Effects of Sevelamer Hydrochloride on the Calcium X Phosphate Product and Lipid Profile of Haemodialysis Patients
    Date
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Title Reply from the Authors
    Date
    Journal Kidney International
    Title Predictive and Pathogenetic Value of Plasma Biomarkers for Acute Kidney Injury in Patients with Acute Lung Injury*
    Date
    Journal Critical Care Medicine
    Excerpt

    OBJECTIVE:: To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury. DESIGN:: Secondary data analysis from a multicenter, randomized clinical trial. SETTING:: Intensive care units in ten university medical centers. PATIENTS:: A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial. INTERVENTIONS:: Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design. MEASUREMENTS AND MAIN RESULTS:: We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-alpha, type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003). CONCLUSIONS:: Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury.

    Title A Comparison of Change in Measured and Estimated Glomerular Filtration Rate in Patients with Nondiabetic Kidney Disease.
    Date
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    BACKGROUND AND OBJECTIVES: All glomerular filtration rate (GFR) estimating equations have been developed from cross-sectional data. The aims of this study were to examine the concordance between use of measured GFR (mGFR) and estimated GFR (eGFR) in tracking changes in kidney function over time among patients with moderately severe chronic kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort study of subjects who had been enrolled in the MDRD Study A and who had two or more contemporaneous assessments of mGFR and eGFR (n = 542; mGFR range, 25 to 55 ml/min per 1.73 m(2)) during the chronic phase (month 4 and afterwards). mGFR was based on urinary iothalamate clearance; eGFR was based on the 4-variable MDRD Study equation. Temporal changes in GFR were assessed by within-subject linear regression of time on GFR. RESULTS: Median follow-up time for all subjects was 2.6 yr; median number of GFR measurements was six. The eGFR slope tended to underestimate measured decrements in GFR. The absolute value of the difference in mGFR and eGFR slopes was <or=2 ml/min per 1.73 m(2) per yr among 58.3% of subjects; the remainder of subjects had larger absolute differences. Among the 22 variables studied, none predicted a systematic difference between mGFR slope and eGFR slope. CONCLUSIONS: Although eGFR and mGFR exhibited similar relationships to 22 baseline variables, the overall bias seen in the full cohort suggests that clinicians and researchers should exercise caution when interpreting eGFR slope as a marker of progression of kidney disease.

    Title Neighborhood Poverty and Kidney Transplantation Among Us Asians and Pacific Islanders with End-stage Renal Disease.
    Date
    Journal American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
    Excerpt

    The degree to which low transplant rates among Asians and Pacific Islanders in the United States are confounded by poverty and reduced access to care is unknown. We examined the relationship between neighborhood poverty and kidney transplant rates among 22 152 patients initiating dialysis during 1995-2003 within 1800 ZIP codes in California, Hawaii and the US-Pacific Islands. Asians and whites on dialysis were distributed across the spectrum of poverty, while Pacific Islanders were clustered in the poorest areas. Overall, worsening neighborhood poverty was associated with lower relative rates of transplant (adjusted HR [95% CI] for areas with > or =20% vs. <5% residents living in poverty, 0.41 [0.32-0.53], p < 0.001). At every level of poverty, Asians and Pacific Islanders experienced lower transplant rates compared with whites. The degree of disparity increased with worsening neighborhood poverty (adjusted HR [95% CI] for Asians-Pacific Islanders vs. whites, 0.64 [0.51-0.80], p < 0.001 for areas with <5% and 0.30 [0.21-0.44], p < 0.001 for areas with > or =20% residents living in poverty; race-poverty level interaction, p = 0.039). High levels of neighborhood poverty are associated with lower transplant rates among Asians and Pacific Islanders compared with whites. Our findings call for studies to identify cultural and local barriers to transplant among Asians and Pacific Islanders, particularly those residing in resource-poor neighborhoods.

    Title Regional Variation in Kidney Transplant Outcomes: Trends Over Time.
    Date
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    BACKGROUND AND OBJECTIVES: Clinical outcomes after kidney transplant have improved considerably in the United States over the past several decades. However, the degree to which this has occurred uniformly across the country is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Regional variations in graft failure after kidney transplant during three different time periods were examined. These time periods were chosen to coincide with major shifts in immunosuppressant usage: Era 1, cyclosporine usage, 1988 through 1989; Era 2, introduction of tacrolimus and mycophenolate mofetil, 1994 through 1995; and Era 3, widespread use of tacrolimus and mycophenolate mofetil, 1998 through 1999. Patient data were obtained from the United States Renal Data System database. For each period, regional differences in time from transplant to graft failure (organ removal, death, or return to dialysis) were examined. For each region, differences in graft failure over time were examined. RESULTS: One-year graft survival rates ranged from 76% to 83% between regions in Era 1 (n = 13,669), from 84% to 89% in Era 2 (n = 17,456), and from 87.5% to 92% in Era 3 (n = 20,375). Three-year graft survival ranged from 65% to 75% between regions in Era 1, from 84% to 89% in Era 2, and from 77% to 86% in Era 3. Adjusted models for donor and recipient characteristics showed improvements in graft survival over time in all United Network for Organ Sharing regions with minimal variation across regions. CONCLUSIONS: Regional differences in graft survival after kidney transplant are minimal, particularly when compared with the dramatic improvements in graft survival that have occurred over time.

    Title Comparison of Proposed Alternative Methods for Rescaling Dialysis Dose: Resting Energy Expenditure, High Metabolic Rate Organ Mass, Liver Size, and Body Surface Area.
    Date
    Journal Seminars in Dialysis
    Excerpt

    A number of denominators for scaling the dose of dialysis have been proposed as alternatives to the urea distribution volume (V). These include resting energy expenditure (REE), mass of high metabolic rate organs (HMRO), visceral mass, and body surface area. Metabolic rate is an unlikely denominator as it varies enormously among humans with different levels of activity and correlates poorly with the glomerular filtration rate. Similarly, scaling based on HMRO may not be optimal, as many organs with high metabolic rates such as spleen, brain, and heart are unlikely to generate unusually large amounts of uremic toxins. Visceral mass, in particular the liver and gut, has potential merit as a denominator for scaling; liver size is related to protein intake and the liver, along with the gut, is known to be responsible for the generation of suspected uremic toxins. Surface area is time-honored as a scaling method for glomerular filtration rate and scales similarly to liver size. How currently recommended dialysis doses might be affected by these alternative rescaling methods was modeled by applying anthropometric equations to a large group of dialysis patients who participated in the HEMO study. The data suggested that rescaling to REE would not be much different from scaling to V. Scaling to HMRO mass would mandate substantially higher dialysis doses for smaller patients of either gender. Rescaling to liver mass would require substantially more dialysis for women compared with men at all levels of body size. Rescaling to body surface area would require more dialysis for smaller patients of either gender and also more dialysis for women of any size. Of these proposed alternative rescaling measures, body surface area may be the best, because it reflects gender-based scaling of liver size and thereby the rate of generation of uremic toxins.

    Title Surface-area-normalized Kt/v: a Method of Rescaling Dialysis Dose to Body Surface Area-implications for Different-size Patients by Gender.
    Date
    Journal Seminars in Dialysis
    Excerpt

    Dialysis is measured as Kt/V, which scales the dose (Kt) to body water content (V). Scaling dialysis dose to body surface area (S(dub)) has been advocated, but the implications of such rescaling have not been examined. We developed a method of rescaling measured Kt/V to S(dub) and studied the effect of such alternative scaling on the minimum adequacy values that might then be applied in male and female patients of varying body size. We examined anthropometric estimates of V and S (Watson vs. Dubois estimates) in 1765 patients enrolled in the HEMO study after excluding patients with amputations. An S-normalized target stdKt/V was defined, and an adequacy ratio (R) was computed for each patient as R = D/N where D = delivered stdKt/V (calculated using the Gotch-Leypoldt equation for stdKt/V) and N = the S-normalized minimum target value. In the HEMO data set, we determined the extent to which baseline (prerandomization) stdKt/V values would have exceeded such an S-based minimum target stdKt/V. The median V(wat):S(dub) ratios were significantly higher in men (21.34) than in women (18.50). The average of these (20) was used to normalize the current suggested minimally adequate value (stdKt/V > or = 2.0/week) to the S-normalized target value (stdKt/S > or = 40 L/M(2)), assuming that average modeled V = average anthropometric V. To achieve this S-normalized target, the required single-pool (sp) Kt/V was always higher in women than in men at any level of body size. For small patients (V(wat) = 25L), required stdKt/V values were 2.05 and 2.21/week for men and women, respectively, corresponding to spKt/V values of 1.31 and 1.52/session. On the other hand, large (V(wat) = 50L) male patients would need spKt/V values of only 1.0/session. Prerandomization baseline dialysis sessions in the HEMO study were found to meet such a new S-based standard in almost all (766/773) men and in 885/992 women. An analysis of scaling dose to anthropometrically estimated liver size (L) showed similar gender ratios for V(wat):L and V(wat):S(dub), providing a potential physiologic explanation underpinning S-based scaling. S-based scaling of the dialysis dose would require considerably higher doses in small patients and in women, and would allow somewhat lower doses in larger male patients. Current dialysis practice would largely meet such an S-based adequacy standard if the dose were normalized to a V(wat):S(dub) ratio of 20.

    Title End Stage Renal Disease.
    Date
    Journal Clinical Evidence
    Excerpt

    End stage renal disease (ESRD) affects over 1500 people per million population in countries with a high prevalence, such as the USA and Japan. Approximately two thirds of people with ESRD receive haemodialysis, a quarter have kidney transplants, and a tenth receive peritoneal dialysis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different doses and osmotic agents for peritoneal dialysis? What are the effects of different doses and membrane fluxes for haemodialysis? What are the effects of interventions aimed at preventing secondary complications? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

    Title Systolic Blood Pressure and Mortality in Prevalent Haemodialysis Patients in the Hemo Study.
    Date
    Journal Journal of Human Hypertension
    Excerpt

    Previous studies of blood pressure and mortality in haemodialysis have yielded mixed results, perhaps due to confounding by comorbid conditions. We hypothesized that after improved accounting for confounding factors, higher systolic blood pressure (SBP) would be associated with higher all-cause mortality. We conducted a secondary analysis of data from the haemodialysis study, a randomized trial in prevalent haemodialysis patients. We used three proportional hazard models to determine the relative hazard at different levels of SBP: (1) Model-BL used baseline SBP; (2) Model-TV used SBP as a time-varying variable; and (3) Model-TV-Lag added a 3-month lag to Model-TV to de-emphasize changes in SBP associated with acute illness. In all the models, pre-dialysis SBP <120 mm Hg was associated with a higher risk of mortality compared with the referent group (140-159 mm Hg); higher pre-dialysis SBP was not associated with higher risk of mortality. In conclusion, we observed a robust association between lower pre-dialysis SBP and higher risk for all-cause and cardiovascular mortality in a well-characterized cohort of prevalent haemodialysis patients. Randomized clinical trials are needed to define optimal blood pressure targets in the haemodialysis population.

    Title Vascular Risk Factors and Cognitive Impairment in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (cric) Study.
    Date
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    Background and objectives Cognitive impairment is common among persons with chronic kidney disease, but the extent to which nontraditional vascular risk factors mediate this association is unclear. Design, setting, participants, & measurements We conducted cross-sectional analyses of baseline data collected from adults with chronic kidney disease participating in the Chronic Renal Insufficiency Cohort study. Cognitive impairment was defined as a Modified Mini-Mental State Exam score >1 SD below the mean score. Results Among 3591 participants, the mean age was 58.2 ± 11.0 years, and the mean estimated GFR (eGFR) was 43.4 ± 13.5 ml/min per 1.73 m(2). Cognitive impairment was present in 13%. After adjustment for demographic characteristics, prevalent vascular disease (stroke, coronary artery disease, and peripheral arterial disease) and traditional vascular risk factors (diabetes, hypertension, smoking, and elevated cholesterol), an eGFR <30 ml/min per 1.73 m(2) was associated with a 47% increased odds of cognitive impairment (odds ratio 1.47, 95% confidence interval 1.05, 2.05) relative to those with an eGFR 45 to 59 ml/min per 1.73 m(2). This association was attenuated and no longer significant after adjustment for hemoglobin concentration. While other nontraditional vascular risk factors including C-reactive protein, homocysteine, serum albumin, and albuminuria were correlated with cognitive impairment in unadjusted analyses, they were not significantly associated with cognitive impairment after adjustment for eGFR and other confounders. Conclusions The prevalence of cognitive impairment was higher among those with lower eGFR, independent of traditional vascular risk factors. This association may be explained in part by anemia.

    Title Living Donor Evaluation and Exclusion: the Stanford Experience.
    Date
    Journal Clinical Transplantation
    Excerpt

    Lapasia JB, Kong S-Y, Busque S, Scandling JD, Chertow GM, Tan JC. Living donor evaluation and exclusion: the Stanford experience.
Clin Transplant 2010 DOI: 10.1111/j.1399-0012.2010.01336.x.
© 2010 John Wiley & Sons A/S. Abstract:  Background:  The proportion of prospective living donors disqualified for medical reasons is unknown. The objective of this study is to delineate and quantify specific reasons for exclusion of prospective living donors from kidney donation. Methods:  All adult prospective kidney donors who contacted our transplant program between October 1, 2007 and April 1, 2009 were included in our analysis (n = 484). Data were collected by review of an electronic transplant database. Results:  Of the 484 prospective donors, 39 (8%) successfully donated, 229 (47%) were excluded, 104 (22%) were actively undergoing evaluation, and 112 (23%) were withdrawn before evaluation was complete. Criteria for exclusion were medical (n = 150), psychosocial (n = 22), or histocompatibility (n = 57) reasons. Of the 150 prospective donors excluded for medical reasons, 79% were excluded because of obesity, hypertension, nephrolithiasis, and/or abnormal glucose tolerance. One hundred and forty-seven (61%) intended recipients had only one prospective living donor, of whom 63 (42%) were excluded. Conclusions:  A significant proportion of prospective living kidney donors were excluded for medical reasons such as obesity (body mass index >30), hypertension, nephrolithiasis, and abnormal glucose tolerance. Longer-term studies are needed to characterize the risks to medically complex kidney donors and the potential risks and benefits afforded to recipients.

    Title Effluent Volume in Continuous Renal Replacement Therapy Overestimates the Delivered Dose of Dialysis.
    Date
    Journal Clinical Journal of the American Society of Nephrology : Cjasn
    Excerpt

    BACKGROUND AND OBJECTIVES: Studies examining dose of continuous renal replacement therapy (CRRT) and outcomes have yielded conflicting results. Most studies considered the prescribed dose as the effluent rate represented by ml/kg per hour and reported this volume as a surrogate of solute removal. Because filter fouling can reduce the efficacy of solute clearance, the actual delivered dose may be substantially lower than the observed effluent rate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were examined from 52 critically ill patients with acute kidney injury (AKI) requiring dialysis. All patients were treated with predilution continuous venovenous hemodiafiltration (CVVHDF) and regional citrate anticoagulation. Filter performance was monitored during the entire course of therapy by measuring blood urea nitrogen (BUN) and dialysis fluid urea nitrogen (FUN) at initiation and every 12 hours. Filter efficacy was assessed by calculating FUN/BUN ratios every 12 hours of filter use. Prescribed urea clearance (K, ml/min) was determined from the effluent rate. Actual delivered urea clearance was determined using dialysis-side measurements. RESULTS: Median daily treatment time was 1413 minutes (1260 to 1440) with a total effluent volume of 46.4 ± 17.4 L and urea mass removal of 13.0 ± 7.6 mg/min. Prescribed clearance overestimated the actual delivered clearance by 23.8%. This gap between prescribed and delivered clearance was related to the decrease in filter function assessed by the FUN/BUN ratio. CONCLUSIONS: Effluent volume significantly overestimates delivered dose of small solutes in CRRT. To assess adequacy of CRRT, solute clearance should be measured rather than estimated by the effluent volume.

    Title The Advance Study: a Randomized Study to Evaluate the Effects of Cinacalcet Plus Low-dose Vitamin D on Vascular Calcification in Patients on Hemodialysis.
    Date
    Journal Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
    Excerpt

    Background. This prospective, randomized, controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone. Methods. Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone (PTH) > 300 pg/mL or PTH 150-300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2) while receiving vitamin D. All subjects received calcium-based phosphate binders. Coronary artery calcification (CAC) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography. Subjects with Agatston CAC scores ≥ 30 were randomized to cinacalcet (30-180 mg/day) plus low-dose calcitriol or vitamin D analog (≤ 2 μg paricalcitol equivalent/dialysis), or flexible vitamin D therapy. The primary end point was percentage change in Agatston CAC score from baseline to Week 52. Results. Median (P10, P90) Agatston CAC scores increased 24% (- 22%, 119%) in the cinacalcet group and 31% (- 9%, 179%) in the flexible vitamin D group (P = 0.073). Corresponding changes in volume CAC scores were 22% (- 12%, 105%) and 30% (- 6%, 133%; P = 0.009). Increases in calcification scores were consistently less in the aorta, aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols, and the differences between groups were significant at the aortic valve. Conclusions. In hemodialysis patients with moderate to severe secondary hyperparathyroidism, cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification.

    Title Sepsis As a Cause and Consequence of Acute Kidney Injury: Program to Improve Care in Acute Renal Disease.
    Date
    Journal Intensive Care Medicine
    Excerpt

    Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI.

    Title End-stage Renal Disease.
    Date
    Journal Clinical Evidence
    Excerpt

    End-stage renal disease (ESRD) affects more than 1500 people per million population in countries with a high prevalence, such as Japan, Taiwan, and the US. Approximately two-thirds of people with ESRD receive haemodialysis, one quarter have kidney transplants, and one tenth receive peritoneal dialysis. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of different doses for peritoneal dialysis? What are the effects of different doses and membrane fluxes for haemodialysis? What are the effects of interventions aimed at preventing secondary complications? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

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