Patient and caregiver knowledge and utilization of partial versus radical nephrectomy: results of a national kidney foundation survey to assess educational needs of kidney cancer patients and caregivers.

BACKGROUND: In response to requests from patients, caregivers, and physicians for information on kidney cancer, the National Kidney Foundation (NKF) conducted a survey to assess the educational needs of the kidney cancer community. Key areas of assessment were patient and caregiver knowledge of risk factors for chronic kidney disease (CKD), including kidney cancer and nephrectomy, and of kidney-sparing surgical options. STUDY DESIGN: Survey to assess educational needs of patients with kidney cancer and caregivers. SETTING & PARTICIPANTS: Respondents were invited through physician referrals and online sources and included 365 adult patients with kidney cancer and 52 caregivers. PREDICTOR: Age, geographic region, and cancer stages 1-2 versus 3-4. OUTCOMES & MEASUREMENTS: Survey responses were descriptively analyzed, with data compared and weighted to the population age and geographic characteristics of the general kidney cancer population. RESULTS: 83% of 181 early-stage patients, 92% of 123 late-stage patients, and 86% of 113 patients who did not know their stage received radical nephrectomy. Although 62% agreed that radical nephrectomy for cancer treatment is a risk factor for CKD, only 40% agreed that losing part or all of 1 kidney from injury or a disease other than cancer is a risk factor for CKD. 56% agreed that kidney cancer can be related to CKD. LIMITATIONS: We did not have patient medical records to validate responses and we do not know the number of people who were invited to take the survey but declined. CONCLUSIONS: There is a lack of patient awareness that kidney cancer and radical nephrectomy are risk factors for CKD. Only a minority of patients underwent partial nephrectomy or were given it as an option for their early-stage kidney cancer. This suggests a knowledge deficit among physicians, surgeons, patients, and caregivers alike that there is a bidirectional relationship between kidney cancer and CKD and that kidney-sparing surgery is preferable when feasible.

Cardiovascular toxicity of epoetin-alfa in patients with chronic kidney disease.

BACKGROUND: Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events. We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin (Hb) irrespective of treatment target and randomized allocation. METHODS: We performed a post hoc analysis from the CHOIR trial. Inclusion criteria were Hb <11.0 g/dl and estimated glomerular filtration rates of 15-50 ml/min/1.73 m(2). To be included in the present analysis, subjects needed to be free of the composite event at 4 months, receive epoetin-alfa, and have ≥1 postbaseline Hb measurement. The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable, while the achieved Hb at month 4 was the confounder representing the subject's underlying response to treatment. The primary outcome was the composite of death, heart failure hospitalization, stroke, or myocardial infarction. A Cox proportional hazard regression model was used in time-to-event analysis. RESULTS: Among 1,244 subjects with complete data, the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure. Cox proportional hazard analysis found that those in the middle tertile of Hb achieved (>11.5 to <12.7 g/dl) and the lowest tertile of epoetin-alfa dose exposure level (<5,164 units/week) had the lowest risk. Irrespective of Hb achieved, the relative risk in the highest tertile (>10,095 units/week) of epoetin-alfa dose exposure level was significantly escalated (hazard ratios ranged from 2.536 to 3.572, p < 0.05, when compared to the group of middle Hb tertile and lowered dose tertile). In a multivariable model that adjusted for achieved Hb, albumin, cholesterol, age, prior heart failure, prior stroke, prior deep venous thrombosis, atrial fibrillation or malignancy, the average weekly dose had a significant (p = 0.005) relative risk of 1.067 per 1,000 units of epoetin-alfa for the primary end point. CONCLUSIONS: In the CHOIR trial, average epoetin-alfa doses >10,095 units/week were associated with increased risks for cardiovascular events irrespective of the Hb achieved within the first 4 months of treatment. These data suggest the weekly epoetin-alfa dose and not the Hb achieved was a principal determinant in the primary outcome observed implicating a cardiovascular toxicity of this erythrocyte-stimulating agent.

Atrial fibrillation: the beat is faster than the answers.

The prevalence of atrial fibrillation is much greater among persons with end-stage renal disease (ESRD) than among the general population. While significant advances have been made recently in the treatment of atrial fibrillation in the general population, we know very little about the treatment of atrial fibrillation among those with ESRD. This Commentary explores gaps in our knowledge of how to treat this vulnerable and sick population.

Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

BACKGROUND: Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. STUDY DESIGN: Secondary analysis of a randomized controlled trial. SETTING & PARTICIPANTS: 1,432 participants with CKD and anemia. INTERVENTION: Participants were randomly assigned to target hemoglobin levels of 13.5 versus 11.3 g/dL with the use of epoetin alfa. OUTCOMES & MEASUREMENTS: Cox regression was used to estimate HRs for progression of CKD (a composite of doubling of creatinine level, initiation of renal replacement therapy, or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate, proteinuria, diabetes, heart failure, and smoking history) also were examined. RESULTS: Participants randomly assigned to higher hemoglobin targets experienced shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03-1.52; P = 0.02) and multivariable models (HR, 1.22; 95% CI, 1.00-1.48; P = 0.05). These differences were attributable to higher rates of renal replacement therapy and death for participants in the high hemoglobin arm. Hemoglobin target did not interact with estimated glomerular filtration rate, proteinuria, diabetes, or heart failure (P > 0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (P = 0.04) such that the higher target had a greater risk of CKD progression for participants who currently smoked (HR, 2.50; 95% CI, 1.23-5.09; P = 0.01), which was not present for those who did not currently smoke (HR, 1.15; 95% CI, 0.93-1.41; P = 0.2). LIMITATIONS: A post hoc analysis; thus, cause and effect cannot be determined. CONCLUSIONS: These results suggest that a high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.

Acute kidney injury and cardiovascular outcomes in acute severe hypertension.

BACKGROUND: Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. METHODS AND RESULTS: The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). CONCLUSIONS: Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

Getting the urine to the lab: time to think outside of the specimen cup.

Rucker and colleagues examine the relationship between distance to a nephrologist and the likelihood of seeing a nephrologist. They demonstrate that increasing distance from a nephrologist has a 'protective effect' against seeing a nephrologist and is associated with a greater risk of hospitalization, a longer hospitalization, and a greater mortality risk. Implications of these associations as well as the mechanisms supporting them are explored.

Veterans more likely to start hemodialysis with an arteriovenous fistula.

Hemodialysis via arteriovenous fistulas (AVFs) is associated with reduced morbidity and mortality when compared to alternative vascular accesses, yet few patients in the United States start dialysis with AVFs. Recent studies have demonstrated higher quality of care for many conditions in Veterans Affairs' Medical Centers (VAMC); however, differences in quality of vascular access care are unknown. We used patient-level data (6/05-5/06) from Medicare claims (n = 25,912) to compare the proportions of AVF among incident patients at VAMC-affiliated (n = 20) and unaffiliated dialysis (n = 1631) facilities. Multivariate logistic regression was used to determine whether associations of access type with facility type were independent. Compared to non-VAMC patients, a larger proportion of VAMC patients started dialysis with AVFs (20.9% versus 11.6% in non-VAMC patients; OR 1.99, [95% CI 1.55-2.56]). Although attenuated, this finding persisted in models adjusted for demographics (OR 1.65 [95% CI 1.28-2.13]) and demographics with comorbidities (OR 1.70 [95% CI 1.31-2.20]). However, after accounting for pre end-stage renal disease (ESRD) care, similar proportions of VAMC and non-VAMC patients started hemodialysis with an AVF (OR 1.28 [95% CI 0.98-1.66]). In conclusion, patients receiving care at VAMC-associated facilities were more likely to start hemodialysis with AVFs, perhaps because of better pre-ESRD care. Nonetheless, AVF rates remain suboptimal, indicating a need for ongoing vascular access evaluation and improvement.

Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors.

BACKGROUND: High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR). METHODS: A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 µg/kg/week) and high-dose (≥ 1 µg/kg/week)). RESULTS: Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 µg/kg/week) vs usual-dose (0.5 µg/kg/week) ESA.In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (rs = 0.39, p = 0.03). In adjusted analyses, higher ESA dose (per µcg/kg/week) was associated with a 53% greater odds of sEpoR being above the median (p < 0.05). CONCLUSION: High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT00526747.

Hypothesis: an erythropoietin honeymoon phase exists.

TREAT was a recently concluded, and well-powered and designed, study of anemia treatment in chronic kidney disease (CKD). Unlike most previous studies of ESA treatment in nondialysis CKD, TREAT was a placebo-controlled trial. The placebo group in TREAT provides a unique long-term view of a conservative approach to anemia management in nondialysis CKD. The course of mean Hgb levels in the placebo group ran counter to expectations, increasing over time. We discuss possible reasons for this, including a new hypothesis that there may be an erythropoietin 'honeymoon phase' similar to that observed in diabetes mellitus. We propose investigation of this phenomenon as it could lead to less expensive and safer approaches to treatment of CKD anemia.

A secondary analysis of the CHOIR trial shows that comorbid conditions differentially affect outcomes during anemia treatment.

The CHOIR trial in anemic patients with chronic kidney disease compared epoetin-alfa treatment with low (11.3 g/l) and high (13.5 g/l) hemoglobin targets on the composite end point of death, hospitalization for heart failure, stroke, and myocardial infarction. However, other anemia management trials in patients with chronic kidney disease found there was increased risk when hemoglobin is targeted above 13 g/dl. In this secondary analysis of the CHOIR trial, we compared outcomes among the subgroups of patients with diabetes and heart failure to describe the comparative relationship of treatment to these two different hemoglobin goals. By Cox regression analysis, there was no increased risk associated with the higher hemoglobin target among patients with heart failure. In patients without heart failure, however, the hazard ratio (1.86) associated with the higher target was significant. Comparing survival curves in an unadjusted model, patients with diabetes did not have a greater hazard associated with the higher target. Subjects without diabetes had a significantly greater hazard in the high as compared to the low target, but the interaction between diabetes and the target was not significant. We suggest that the increased risks associated with higher hemoglobin targets are not clinically apparent among subgroups with greater mortality risk. These differential outcomes underscore the need for dedicated trials in these subpopulations.

Cystatin C, albuminuria, and 5-year all-cause mortality in HIV-infected persons.

BACKGROUND: Compared with controls, human immunodeficiency virus (HIV)-infected persons have a greater prevalence of kidney disease, assessed according to high cystatin C level and albuminuria, but not according to creatinine level. However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied. STUDY DESIGN: We conducted an observational cohort study to determine the association of kidney disease (measured according to albuminuria, cystatin C, and serum creatinine) with mortality. SETTING & PARTICIPANTS: 922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) Study. PREDICTOR: Serum cystatin C and serum creatinine levels were used to estimate glomerular filtration rates (eGFR(SCysC) and eGFR(SCr), respectively). Albuminuria was defined as a positive urine dipstick result (≥ 1+) or urine albumin-creatinine ratio >30 mg/g. OUTCOME: 5-Year mortality. RESULTS: At baseline, decreased kidney function (eGFR(SCysC) <60 mL/min/1.73 m(2)) or albuminuria was present in 28% of participants. After 5 years of follow-up, mortality was 48% in those with both eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria, 23% in those with eGFR(SCysC) < 60 mL/min/1.73 m(2) alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory marker levels, eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria were associated with a nearly 2-fold increase in mortality, whereas eGFR(SCr) < 60 mL/min/1.73 m(2) did not appear to have a substantial association with mortality. Together, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria accounted for 17% of the population-level attributable risk of mortality. LIMITATIONS: Vital status was unknown in 261 participants from the original cohort. CONCLUSIONS: Kidney disease marked by albuminuria or increased cystatin C level appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.

Perioperative outcomes among patients with end-stage renal disease following coronary artery bypass surgery in the USA.

BACKGROUND: Patients with end-stage renal disease (ESRD) requiring chronic haemodialysis who undergo coronary artery bypass graft surgery (CABG) are at significant risk for perioperative mortality. However, the impact of changes in ESRD patient volume and characteristics over time on operative outcomes is unclear. METHODS: Using the Nationwide Inpatient Sample database (1988-03), we evaluated rates of CABG surgery with and without concurrent valve surgery among ESRD patients and outcomes including in-hospital mortality, and length of hospital stay. Multivariate regression models were used to account for patient characteristics and potential cofounders. RESULTS: From 1988 to 2003, annual rates of CABG among ESRD patients doubled from 2.5 to 5 per 1000 patient-years. Concomitantly, patient case-mix changed to include patients with greater co-morbidities such as diabetes, hypertension and obesity (all P < 0.001). Nonetheless, among ESRD patients, in-hospital mortality rates declined nearly 6-fold from over 31% to 5.4% (versus 4.7% to 1.8% among non-ESRD), and the median length of in-hospital stay dropped in half from 25 to 13 days (versus 14 to 10 days among non-ESRD). CONCLUSIONS: Since 1988, an increasing number of patients with ESRD have been receiving CABG in the USA. Despite increasing co-morbidities, operative mortality rates and length of in-hospital stay have declined substantially. Nonetheless, mortality rates remain almost 3-fold higher compared to non-ESRD patients indicating a need for ongoing improvement.

Randomized evaluation of efficacy and safety of ferric carboxymaltose in patients with iron deficiency anaemia and impaired renal function (REPAIR-IDA): rationale and study design.

BACKGROUND: Patients with iron deficiency anaemia (IDA) in the setting of non-dialysis-dependent chronic kidney disease (NDD-CKD) may benefit from treatment with intravenous (IV) iron. Ferric carboxymaltose (FCM) is a novel IV iron formulation designed to permit larger infusions compared to currently available IV standards such as Venofer(R) (iron sucrose). METHODS: The primary objective of REPAIR-IDA is to estimate the cardiovascular safety and efficacy of FCM (two doses at 15 mg/kg to a maximum of 750 mg per dose) compared to Venofer(R) (1000 mg administered as five infusions of 200 mg) in subjects who have IDA and NDD-CKD. REPAIR-IDA is a multi-centre, randomized, active-controlled, open-label study. Eligible patients must have haemoglobin (Hgb) < or = 11.5 g/dL and CKD defined as (1) GFR < 60 mL/min/1.73 m(2) on two occasions or (2) GFR < 90 mL/min/1.73 m(2) and either evidence of renal injury by urinalysis or elevated Framingham cardiovascular risk score. Two thousand and five hundred patients will be randomized to FCM or Venofer(R) in a 1:1 ratio. The primary efficacy endpoint is mean change in Hgb from baseline to the highest observed Hgb between baseline and Day 56. The primary safety endpoint is the proportion of subjects experiencing at least one of the following events: death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalization, congestive heart failure requiring hospitalization or medical intervention, arrhythmias, hypertension or hypotension during the 120 days following randomization. CONCLUSION: REPAIR-IDA will assess the efficacy and safety of two 750-mg infusions of FCM compared to an FDA-approved IV iron regimen in patients with NDD-CKD at increased risk for cardiovascular disease.

Decreased pulse pressure during hemodialysis is associated with improved 6-month outcomes.

Pulse pressure is a well established marker of vascular stiffness and is associated with increased mortality in hemodialysis patients. Here we sought to determine if a decrease in pulse pressure during hemodialysis was associated with improved outcomes using data from 438 hemodialysis patients enrolled in the 6-month Crit-Line Intradialytic Monitoring Benefit Study. The relationship between changes in pulse pressure during dialysis (2-week average) and the primary end point of non-access-related hospitalization and death were adjusted for demographics, comorbidities, medications, and laboratory variables. In the analyses that included both pre- and post-dialysis pulse pressure, higher pre-dialysis and lower post-dialysis pulse pressure were associated with a decreased hazard of the primary end point. Further, every 10 mm Hg decrease in pulse pressure during dialysis was associated with a 20% lower hazard of the primary end point. In separate models that included pulse pressure and the change in pulse pressure during dialysis, neither pre- nor post-dialysis pulse pressure were associated with the primary end point, but each 10 mm Hg decrease in pulse pressure during dialysis was associated with about a 20% lower hazard of the primary end point. Our study found that in prevalent dialysis subjects, a decrease in pulse pressure during dialysis was associated with improved outcomes. Further study is needed to identify how to control pulse pressure to improve outcomes.

The effects of HIV type-1 viral suppression and non-viral factors on quantitative proteinuria in the highly active antiretroviral therapy era.

BACKGROUND: Proteinuria is associated with progressive renal disease and overall mortality in HIV-infected patients; however, the prevalence and correlates of quantitative proteinuria in the highly active antiretroviral therapy era are unknown. METHODS: Spot urine protein to creatinine (P/Cr) ratios, an accepted measure of quantitative daily proteinuria, were measured annually since 2002 in participants of the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort. We used linear regression models with general estimating equations to identify factors associated with the abnormal P/Cr thresholds of >/=0.2 and >/=1.0. RESULTS: Of the 2,857 participants (most of whom were receiving antiretroviral therapy) analysed, 16% and 3% had P/Cr levels >/=0.2 and >/=1.0, respectively, at first measurement. P/Cr levels did not change during a median follow-up of 3 years (interquartile range 2-4). Factors associated with P/Cr>/=0.2 at any measurement included greater age, lower glomerular filtration rate, female sex, antiretroviral therapy prior to entry into parent randomized trial, HIV type-1 RNA level >/=400 copies/ml, lower CD4(+) T-cell count and history of hypertension, diabetes or hepatitis C coinfection (all P<0.04). Black race and higher non-high-density lipoprotein cholesterol levels were associated with P/Cr levels >/=1.0, but not with P/Cr levels >/=0.2. Hepatitis B coinfection and current use of adefovir, indinavir and tenofovir were not associated with either of the P/Cr thresholds. CONCLUSIONS: Both HIV-1 and non-HIV-1-related factors are associated with abnormal levels of proteinuria and identify those who are at a greater risk of worse clinical outcomes. Several of these factors are differentially associated with lower and higher proteinuria thresholds.

Association of blood pressure increases during hemodialysis with 2-year mortality in incident hemodialysis patients: a secondary analysis of the Dialysis Morbidity and Mortality Wave 2 Study.

BACKGROUND: Intradialytic increases in blood pressure (BP) can complicate the management of hypertension in hemodialysis (HD) patients. However, the long-term consequences are uncertain. Thus, we sought to determine whether BP increases during HD were associated with greater 2-year mortality in incident HD patients. STUDY DESIGN: Secondary analysis of a prospective dialysis cohort. SETTING & PARTICIPANTS: Incident HD patients in the Dialysis Morbidity and Mortality Wave 2 Study. PREDICTORS: Changes in systolic BP (SBP) during HD (ie, postdialysis SBP -- predialysis SBP), averaged from 3 HD sessions before enrollment. OUTCOME: Time to 2-year all-cause mortality. MEASUREMENTS: Cox regression was used to model hazard ratios for mortality associated with changes in SBP during HD while adjusting for demographics, comorbid conditions, interdialytic weight gain, laboratory variables, and antihypertensive agents. RESULTS: Of 1,748 patients, 12.2% showed greater than 10-mm Hg increases in SBP during HD. In adjusted analyses, every 10-mm Hg increase in SBP during HD was associated independently with a 6% increased hazard of death (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.11). When also adjusted for diastolic BP and postdialysis SBP, the adjusted hazard of death associated with increasing SBP during HD remained significant (hazard ratio, 1.12; 95% confidence interval, 1.05 to 1.21 per 10-mm Hg increase in SBP during HD). However, in analyses adjusted for predialysis SBP, there was a significant interaction between change in SBP and predialysis SBP. In analyses stratified by predialysis SBP, trends for increased mortality associated with increasing SBP during dialysis were present in patients with predialysis SBP less than 160 mm Hg. However, this relationship was significant only in patients with predialysis SBP less than 120 mm Hg. LIMITATIONS: Secondary analysis with a limited number of baseline BP measurements and limited information about dialysis prescription. CONCLUSIONS: Increasing SBP by more than 10 mm Hg during HD occurs in approximately 10% of incident patients, and although increasing SBP during HD was associated with decreased 2-year survival, these findings were limited to patients with predialysis SBP less than 120 mm Hg.

Phosphate binders in chronic kidney disease and end-stage renal disease: a patient-centered approach.

Disorders of calcium and phosphorus metabolism are associated with significant morbidity and mortality in patients with advanced chronic kidney disease. These patients typically require oral phosphate binders to maintain phosphorus homeostasis, but the choice of which among several agents to use has been actively investigated and debated. Recent debate has been polarized between those who favor calcium-based binders for their proven efficacy and relatively low cost and those who favor sevelamer for its putative beneficial effects on inflammatory biomarkers and vascular calcification. This review summarizes the current state of the art of prescribing phosphate binders, ranging from large-scale clinical trials to focused mechanistic studies, and proposes that the available evidence does not conclusively prove the relative superiority of any one binder.

Medical costs of abnormal serum sodium levels.

An abnormal serum sodium level is the most common electrolyte disorder in the United States and can have a significant impact on morbidity and mortality. The direct medical costs of abnormal serum sodium levels are not well understood. The impact of hyponatremia and hypernatremia on 6-mo and 1-yr direct medical costs was examined by analyzing data from the Integrated HealthCare Information Services National Managed Care Benchmark Database. During the period analyzed, there were 1274 patients (0.8%) with hyponatremia (serum sodium <135 mmol/L), 162,829 (97.3%) with normal serum sodium levels, and 3196 (1.9%) with hypernatremia (>145 mmol/L). Controlling for age, sex, region, and comorbidities, hyponatremia was a significant independent predictor of costs at 6 mo (41.2% increase in costs; 95% confidence interval, 30.3% to 53.0%) and at 1 yr (45.7% increase; 95% confidence interval, 34.2% to 58.2%). Costs associated with hypernatremia were not significantly different from those incurred by patients with normal serum sodium. In conclusion, hyponatremia is a significant independent predictor of 6-mo and 1-yr direct medical costs.

Renal dysfunction and tenofovir toxicity in HIV-infected patients.

Potentially nephrotoxic drugs are only 1 of several causes of renal dysfunction in HIV. Data from the period before the wide use of tenofovir show a variety of prerenal, renal, and obstructive causes of acute renal failure (ARF) in HIV outpatients. Results of clinical trials of tenofovir indicate a rate of ARF of approximately 1%, with observational cohort data indicating a somewhat higher rate. Thus, in evaluating patients with rising serum creatinine levels, including those receiving tenofovir, diagnostic efforts should go beyond discontinuation of potentially offending drugs. This article summarizes a presentation on renal dysfunction in HIV and renal toxicity of antiretroviral drugs made by Lynda A. Szczech, MD, MSCE, at an International AIDS Society-USA Continuing Medical Education course in Washington, DC, in May 2008. The original presentation is available as a Webcast at www.iasusa.org.

Negative trials in nephrology: what can we learn?

Chronic kidney disease is assuming epidemic proportions, and an increasing number of clinical trials are testing treatments developed to improve morbidity and mortality. Surprisingly, however, a large proportion of these trials have had negative or neutral results. When trials unexpectedly demonstrate either no benefit or a detrimental impact of a treatment, especially when that treatment is already used in practice, critics commonly argue that the results were dictated by flawed trial design rather than the intrinsic properties of the treatment. In kidney disease therapeutics, trials commonly rely on observational data and test the hypothesis that these associations may be extrapolated to cause-and-effect. Other key issues in trial design that may affect outcomes include the impact of enrolling relatively healthier subjects, the complexity of recruiting participants with specific characteristics while maintaining generalizability, and the subtleties of event adjudication and quality of life assessments. In this article, general principles of trial design will be discussed and the potential lessons learned from recent trials in nephrology will be critically reviewed.