Targeting Gut Microbiome With Prebiotic in Patients With CKD: The TarGut-CKD Study.

Introduction: Disruption of gut microbiota underpins some of the metabolic alterations observed in chronic kidney disease (CKD). Methods: In a nonrandomized, open-label, 3-phase pilot trial, with repeated measures within each phase, we examined the efficacy of oligofructose-enriched inulin (p-inulin) in changing the gut microbiome and their metabolic products in 15 patients with CKD. The stability of microbiome and metabolome was studied during the pretreatment phase (8 weeks), a p-inulin treatment phase (12 weeks), and a post treatment phase (8 weeks) of the study. Results: Study participants completed 373 of the 420 expected study visits (88.8%). Adherence to p-inulin was 83.4%. 16S rRNA sequencing was performed in 368 stool samples. A total of 1085 stool, urine, and plasma samples were subjected to untargeted metabolomic studies. p-inulin administration altered the composition of the gut microbiota significantly, with an increase in abundance of Bifidobacterium and Anaerostipes. Intersubject variations in microbiome and metabolome were larger than intrasubject variation, indicating the stability of the gut microbiome within each phase of the study. Overall metabolite compositions assessed by beta diversity in urine and stool metabolic profiles were significantly different across study phases. Several specific metabolites in stool, urine, and plasma were significant at false discovery rate (FDR) ≤ 0.1 over phase. Specifically, there was significant enrichment in microbial metabolites derived from saccharolysis. Conclusion: Results from our study highlight the stability of the gut microbiome and the expansive effect of p-inulin on microbiome and host cometabolism in patients with CKD. Findings from this study will enable rigorous design of microbiome-based intervention trials.

Study protocol of a randomized controlled trial of fistula vs. graft arteriovenous vascular access in older adults with end-stage kidney disease on hemodialysis: the AV access trial.

BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).

Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

Abnormalities in Cardiac Structure and Function among Individuals with CKD: The COMBINE Trial.

Background: Individuals with CKD have a high burden of cardiovascular disease (CVD). Abnormalities in cardiac structure and function represent subclinical CVD and can be assessed by cardiac magnetic resonance imaging (cMRI). Methods: We investigated differences in cMRI parameters in 140 individuals with CKD stages 3b-4 who participated in the CKD Optimal Management with BInders and NicotinamidE (COMBINE) trial and in 24 age- and sex-matched healthy volunteers. Among COMBINE participants, we examined the associations of eGFR, urine albumin-creatinine ratio (UACR), phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) with baseline (N=140) and 12-month change (N=112) in cMRI parameters. Results: Mean (SD) ages of the COMBINE participants and healthy volunteers were 64.9 (11.9) and 60.4 (7.3) years, respectively. The mean (SD) baseline eGFR values in COMBINE participants were 32.1 (8.0) and 85.9 (16.0) ml/min per 1.73 m2 in healthy volunteers. The median (interquartile range [IQR]) UACR in COMBINE participants was 154 (20.3-540.0) mg/g. Individuals with CKD had lower mitral valve E/A ratio compared with healthy volunteers (for CKD versus non-CKD, ß estimate, -0.13; 95% CI, -0.24 to -0.012). Among COMBINE participants, multivariable linear regression analyses showed that higher UACR was significantly associated with lower mitral valve E/A ratio (ß estimate per 1 unit increase in natural-log UACR, -0.06; 95% CI, -0.09 to -0.03). This finding was preserved among individuals without baseline CVD. UACR was not associated with 12-month change in any cMRI parameter. eGFR, phosphate, FGF23, and PTH were not associated with any cMRI parameter in cross-sectional or change analyses. Conclusions: Individuals with CKD stages 3b-4 have evidence of cMRI abnormalities. Albuminuria was independently associated with diastolic dysfunction, as assessed by mitral valve E/A ratio, in individuals with CKD with and without clinical CVD. Albuminuria was not associated with change in any cMRI parameter.

Surgical versus percutaneous catheter placement for peritoneal dialysis: an updated systematic review and meta-analysis.

BACKGROUND: No consensus currently exists regarding the optimal approach for peritoneal dialysis catheter placement. We aimed to compare the outcomes of percutaneous and surgical peritoneal dialysis catheter placement. METHODS: A systematic review of the literature was performed using the MEDLINE, Cochrane Library, and Scopus databases (end-of-search date: August 29th, 2020). We included studies comparing percutaneous (blind, under fluoroscopic/ultrasound guidance, and "half-perc") and surgical peritoneal dialysis catheter placement (open and laparoscopic) in terms of their infectious complications (peritonitis, tunnel/exit-site infections), mechanical complications (leakage, inflow/outflow obstruction, migration, hemorrhage, hernia, bowel perforation) and long-term outcomes (malfunction, removal, replacement, surgery required, and mortality). RESULTS: Thirty-four studies were identified, including thirty-two observational studies (twenty-six retrospective and six prospective) and two randomized controlled trials. Percutaneous placement was associated with significantly lower rates of tunnel/exit-site infection [relative risk (RR) 0.72, 95% confidence interval (CI) 0.56-0.91], catheter migration (RR 0.68, 95% CI 0.49, 0.95), and catheter removal (RR 0.73, 95% CI 0.60-0.88). The 2-week and 4-week rates of early tunnel/exit-site infection were also lower in the percutaneous group (RR 0.45, 95% CI 0.22-0.93 and RR 0.41, 95% CI 0.27-0.63, respectively). No statistically significant difference was observed regarding other outcomes, including catheter survival and mechanical complications. CONCLUSION: Overall, the quality of published literature on the field of peritoneal dialysis catheter placement is poor, with a small percentage of studies being randomized clinical trials. Percutaneous peritoneal dialysis catheter placement is a safe procedure and may result in fewer complications, such as tunnel/exit-site infections, and catheter migration, compared to surgical placement. PROTOCOL REGISTRATION: PROSPERO CRD42020154951.

Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD.

BACKGROUND AND OBJECTIVES: Kidney functional magnetic resonance imaging (MRI) requires further investigation to enhance the noninvasive identification of patients at high risk of CKD progression. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this exploratory study, we obtained baseline diffusion-weighted and blood oxygen level-dependent MRI in 122 participants of the CKD Optimal Management with Binders and Nicotinamide trial, which was a multicenter, randomized, double-blinded, 12-month, four-group parallel trial of nicotinamide and lanthanum carbonate versus placebo conducted in individuals with eGFR 20-45 ml/min per 1.73 m2. Lower values of apparent diffusion coefficient (ADC) on diffusion-weighted MRI may indicate increased fibrosis, and higher values of relaxation rate (R2*) on blood oxygen level-dependent MRI may represent decreased oxygenation. Because there was no effect of active treatment on eGFR over 12 months, we tested whether baseline kidney functional MRI biomarkers were associated with eGFR decline in all 122 participants. In a subset of 87 participants with 12-month follow-up MRI data, we evaluated whether kidney functional MRI biomarkers change over time. RESULTS: Mean baseline eGFR was 32±9 ml/min per 1.73 m2, and mean annual eGFR slope was -2.3 (95% confidence interval [95% CI], -3.4 to -1.1) ml/min per 1.73 m2 per year. After adjustment for baseline covariates, baseline ADC was associated with change in eGFR over time (difference in annual eGFR slope per 1 SD increase in ADC: 1.3 [95% CI, 0.1 to 2.5] ml/min per 1.73 m2 per year, ADC×time interaction P=0.04). This association was no longer significant after further adjustment for albuminuria (difference in annual eGFR slope per 1 SD increase in ADC: 1.0 (95% CI, -0.1 to 2.2) ml/min per 1.73 m2 per year, ADC×time interaction P=0.08). There was no significant association between baseline R2* and change in eGFR over time. In 87 participants with follow-up functional MRI, ADC and R2* values remained stable over 12 months (intraclass correlation: 0.71 and 0.68, respectively). CONCLUSIONS: Baseline cortical ADC was associated with change in eGFR over time, but this association was not independent of albuminuria. Kidney functional MRI biomarkers remained stable over 1 year. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CKD Optimal Management with Binders and Nicotinamide (COMBINE), NCT02258074.

A Randomized Trial Comparing the Safety, Adherence, and Pharmacodynamics Profiles of Two Doses of Sodium Bicarbonate in CKD: the BASE Pilot Trial.

BACKGROUND: Oral sodium bicarbonate (NaHCO3) may preserve kidney function in CKD, even if initiated when serum bicarbonate concentration is normal. Adequately powered trials testing this hypothesis have not been conducted, partly because the best dose for testing is unknown. METHODS: This multicenter pilot trial assessed the safety, tolerability, adherence, and pharmacodynamics of two doses of NaHCO3 over 28 weeks in adults with eGFR 20-44 or 45-59 ml/min per 1.73 m2 with urinary albumin/creatinine (ACR) ≥50 mg/g and serum bicarbonate 20-28 meq/L. We randomly assigned 194 participants from ten clinical sites to receive higher-dose (HD-NaHCO3; 0.8 meq/kg of lean body wt per day; n=90) or lower-dose (LD-NaHCO3; 0.5 meq/kg of lean body wt per day; n=52) NaHCO3 or matching placebo (n=52). The dose was adjusted depending on side effects. The prescribed dose at week 28 was the primary outcome; a dose was considered acceptable for a full-scale trial if ≥67% of participants were on full-dose and ≥80% were on ≥25% of the per-protocol dose. RESULTS: Mean±SD baseline eGFR was 36±9 ml/min per 1.73 m2, serum bicarbonate was 24±2 meq/L, and median (IQR) ACR was 181 (25-745) mg/g. Both doses were well tolerated without significant changes in BP, weight, or serum potassium. The proportions of adverse events and hospitalizations were similar across the groups. Consequently, 87% in HD-NaHCO3, 96% in LD-NaHCO3, and 87% in placebo were on full dose at week 28; and 91% in HD-NaHCO3, 98% in LD-NaHCO3, and 92% in placebo were on ≥25% of the per-protocol dose. Mean urinary ammonium excretion was 25% lower and serum bicarbonate concentration was 1.3 meq/L higher in HD-NaHCO3 compared with LD-NaHCO3 at week 28. However, mean ACR increased by 12% in the lower-dose group and 30% in the higher-dose group. CONCLUSIONS: Both NaHCO3 doses were well tolerated over 28 weeks with no significant difference in adverse events or hospitalization compared with placebo. The higher dose lowered urinary ammonium excretion and increased serum bicarbonate more than the lower dose but was associated with a greater increase in ACR. The higher 0.8 meq/kg of lean body wt per day dose of NaHCO3 may be a reasonable choice for future trials.

Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial.

BACKGROUND: Higher serum phosphate and fibroblast growth factor-23 (FGF23) levels may be modifiable to prevent cardiovascular disease in CKD. Short-term studies have reported modest efficacy in phosphate and FGF23 reduction with intestinal phosphate binders in CKD. METHODS: To investigate effects of lanthanum carbonate (LC; a phosphate binder) and/or nicotinamide (NAM; an inhibitor of active intestinal phosphate transport) on serum phosphate and FGF23 in stage 3b/4 CKD, we conducted a randomized trial among individuals with eGFR 20-45 ml/min per 1.73 m2 to NAM (750 mg twice daily) plus LC (1000 mg thrice daily), NAM plus LC placebo, LC plus NAM placebo, or double placebo for 12 months. Dual primary end points were change from baseline in serum phosphate and intact FGF23 concentrations. RESULTS: Mean eGFR for the 205 participants was 32ml/min per 1.73 m2. At baseline, serum phosphate was 3.7 mg/dl and median FGF23 was 99 pg/ml (10th, 90th percentiles: 59, 205). Mean rates of change in phosphate increased slightly over 12 months in all groups and did not differ significantly across arms. Similarly, percent changes in FGF23 per 12 months increased for all arms except LC plus placebo, and did not differ significantly across arms. Gastrointestinal symptoms limited adherence. Adverse events rates were similar across arms. CONCLUSIONS: LC and/or NAM treatment did not significantly lower serum phosphate or FGF23 in stage 3b/4 CKD over 12 months. Although these agents appeared safe, intestinal symptoms limited adherence. Reducing phosphate and FGF23 in nondialysis CKD will require new approaches.

Working Toward an Improved Understanding of Chronic Cardiorenal Syndrome Type 4.

Chronic diseases of the heart and of the kidneys commonly coexist in individuals. Certainly combined and persistent heart and kidney failure can arise from a common pathologic insult, for example, as a consequence of poorly controlled hypertension or of severe diffuse arterial disease. However, strong evidence is emerging to suggest that cross talk exists between the heart and the kidney. Independent processes are set in motion when kidney function is chronically diminished, and these processes can have distinct adverse effects on the heart. The complex chronic heart condition that results from chronic kidney disease (CKD) has been termed cardiorenal syndrome type 4. This review will include an updated description of the cardiac morphology in patients who have CKD, an overview of the most likely CKD-sourced culprits for these cardiac changes, and the potential therapeutic strategies to limit cardiac complications in patients who have CKD.

Serum Potassium Levels and Risk of Sudden Cardiac Death Among Patients With Chronic Kidney Disease and Significant Coronary Artery Disease.

INTRODUCTION: Chronic kidney disease (CKD) patients have increased risks of sudden cardiac arrest and sudden cardiac death (SCA/SCD) that are not explained by traditional risk factors. We examined associations between serum potassium and SCA/SCD in a large cohort of patients with coronary artery disease (CAD) and moderate CKD. METHODS: Among 22,009 patients who underwent cardiac catheterization at our institution between 1999 and 2011, 6181 patients had an estimated glomerular filtration rate of ≤60 ml/min per 1.73 m2 and were not receiving renal replacement therapy. The risk of SCA/SCD and all-cause mortality associated with potassium concentration was evaluated at the time of cardiac catheterization (baseline) and most proximate to SCA/SCD events. Covariate-adjusted Cox models were used to examine relationships between baseline potassium measurements and outcomes. A propensity score-matched, case-control design was used to assess risk associations of potassium measurements obtained proximate to SCA events. RESULTS: In the baseline potassium analysis, compared with levels in the normal range, there was no significant risk association between hyperkalemia (>5 mEq/l) or hypokalemia (<3.5 mEq/l) and SCA/SCD or all-cause death after covariate adjustment. In the proximate potassium analysis, hyperkalemia occurred more frequently than hypokalemia (16.7% vs. 3%), and was associated with a doubling in SCA/SCD risk (adjusted odd ratio: 2.37; 95% confidence interval: 1.33-4.23) whereas there was no significant relationship between hypokalemia and outcome. DISCUSSION: Among CKD patients with significant CAD, elevated serum potassium levels >5.0 mEq/l are common and are associated with an increased short-term risk of SCA/SCD. Early detection and treatment of hyperkalemia may reduce the high risk of SCD among CKD patients.

Dialysate Potassium, Dialysate Magnesium, and Hemodialysis Risk.

One of the fundamental goals of the hemodialysis prescription is to maintain serum potassium levels within a narrow normal range during both the intradialytic and interdialytic intervals. Considering the extraordinarily high rate of cardiovascular mortality in the hemodialysis population, clinicians are obligated to explore whether factors related to dialytic potassium removal can be modified to improve clinical outcomes. Observational studies and circumstantial evidence suggest that extreme concentrations of serum and dialysate potassium can trigger cardiac arrest. In this review, we provide an overview of factors affecting overall potassium balance and factors modulating potassium dialysate fluxes in dialysis, and we review data linking serum and dialysate potassium concentrations with arrhythmias, cardiovascular events, and mortality. We explore potential interactions between serum and dialysate magnesium levels and risks associated with dialysate potassium levels. Finally, we conclude with proposed dialytic and novel nondialytic approaches to optimize outcomes related to potassium homeostasis in patients on hemodialysis. Dialysis clinicians need to consider changes in the overall clinical scenario when choosing dialysate potassium concentrations, and an effective change in practice will require more frequent serum potassium monitoring and responsive dialysis care teams.

Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial.

Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.

Clinical Outcomes in Dialysis Patients: Prospects for Improvement with Aldosterone Receptor Antagonists.

Patients with advanced chronic kidney disease (CKD), particularly those who have end-stage renal disease (ESRD) and require therapy with dialysis, suffer disproportionately from cardiovascular illnesses. Therapy with mineralocorticoid receptor antagonists (MRAs) effectively reduces cardiac risk in discrete populations. Blockade of the mineralocorticoid receptor carries the potential to reduce blood pressure and to promote favorable remodeling of cardiac structure. Preliminary observations suggest that MRAs can improve survival in patients with ESRD though their widespread adoption is tempered by concerns about effectiveness in patients who have reduced kidney function and the risks of hyperkalemia. This generates a particular conundrum, as sudden cardiac arrest is the predominant cause of death in patients with advanced CKD. In this review, we highlight the potential cardiovascular benefits and review the evident risks of MRAs in patients with ESRD.

Primary prevention implantable cardioverter defibrillators in end-stage kidney disease patients on dialysis: a matched cohort study.

BACKGROUND: Sudden cardiac death is the leading cause of death among end-stage kidney disease patients (ESKD) on dialysis, but the benefit of primary prevention implantable cardioverter defibrillators (ICDs) in this population is uncertain. We conducted this investigation to compare the mortality of dialysis patients receiving a primary prevention ICD with matched controls. METHODS: We used data from the National Cardiovascular Data Registry's ICD Registry to select dialysis patients who received a primary prevention ICD, and the Get with the Guidelines-Heart Failure Registry to select a comparator cohort. We matched ICD recipients and no-ICD patients using propensity score techniques to reduce confounding, and overall survival was compared between groups. RESULTS: We identified 108 dialysis patients receiving primary prevention ICDs and 195 comparable dialysis patients without ICDs. One year (3-year) mortality was 42.2% (68.8%) in the ICD registry cohort compared with 38.1% (75.7%) in the control cohort. There was no significant survival advantage associated with ICD [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.66-1.13, log-rank P = 0.29]. After propensity matching, our analysis included 86 ICD patients and 86 matched controls. Comparing the propensity-matched cohorts, 1 year (3 years) mortality was 43.4% (74.0%) in the ICD cohort and 39.7% (76.6%) in the control cohort; there was no significant difference in mortality outcome between groups (HR = 0.94, 95% CI: 0.67-1.31, log-rank P = 0.71). CONCLUSIONS: We did not observe a significant association between primary prevention ICDs and reduced mortality among ESKD patients receiving dialysis. Consideration of the potential risks and benefits of ICD implantation in these patients should be undertaken while awaiting the results of definitive clinical trials.

Prescriptions for dietary sodium in patients with chronic kidney disease: how will this shake out?

Patients with chronic kidney disease (CKD) are at risk of exhibiting expanded extracellular volume, and low-sodium diets are often prescribed to limit clinical complications from this condition. Fan et al. performed a post hoc study from the database of the Modification of Diet in Renal Disease Study. Their article, as well as other recent observations, suggests that a low-sodium diet may not be as beneficial as previously thought in all CKD patients.

Sudden cardiac arrest in ESRD patients.

End-stage renal disease (ESRD) carries a significant risk for sudden cardiac arrest (SCA), hospitalization and mortality. We present a case of a vintage hemodialysis patient who had a catastrophic event during his hemodialysis treatment - a sudden cardiac arrest. This case raises several important issues: First, patients with chronic kidney disease (CKD) (and particularly ESRD) are predisposed to an inordinate risk of SCA; second, the factors leading to SCA in CKD are unique; and lastly, it is of paramount importance to have basic life support training, crash carts and defibrillators in dialysis units. It also raises the important discussion regarding the role for automated implantable cardioverter defibrillators and medical therapy for the prevention of SCA in this population.

Analysis of early hypertension and clinical outcome with bevacizumab: results from seven phase III studies.

BACKGROUND: Hypertension is associated with antivascular endothelial growth factor treatment, but the clinical implications of hypertension are uncertain. To assess the prognostic and predictive value of bevacizumab-related hypertension, a comprehensive analysis of whether hypertension and efficacy outcomes are associated was conducted on seven company-sponsored placebo-controlled phase III studies of bevacizumab. METHODS: Patient-specific data were available from 6,486 patients with metastatic colorectal, breast, non-small cell lung, pancreatic, and renal cell cancers. Primary hypertension endpoint was a blood pressure (BP) increase of >20 mmHg systolic or >10 mmHg diastolic within the first 60 days of treatment. Additional endpoints included other predefined thresholds of change in BP and severity of hypertension graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events. To analyze the general prognostic importance of an early BP increase, multivariate Cox regression models were used to assess the correlation between BP changes and progression-free (PFS) and overall survival (OS) outcomes in the control groups. To analyze whether early BP increases could predict for benefit from bevacizumab, similar analyses were conducted in the bevacizumab-treated and control groups. RESULTS: In six of seven studies, early BP increase was neither predictive of clinical benefit from bevacizumab nor prognostic for the course of the disease. For study AVF2107g, early increased BP was associated with longer PFS and OS times in the bevacizumab group but shorter OS time in the control group. CONCLUSIONS: Early treatment-related BP increases do not predict clinical benefit from bevacizumab based on PFS or OS outcomes. BP increases do not appear to have general prognostic importance for patients with advanced cancer.

Dialysate calcium concentration and the risk of sudden cardiac arrest in hemodialysis patients.

BACKGROUND AND OBJECTIVES: The optimal dialysate calcium concentration to maintain normal mineralization and reduce risk of cardiovascular events in hemodialysis patients is debated. Guidelines suggest that dialysate Ca concentration should be lowered to avoid vascular calcification, but cardiac arrhythmias may be more likely to occur at lower dialysate Ca. Concurrent use of QT-prolonging medications may also exacerbate arrhythmic risk. This study examined the influence of serum Ca, dialysate Ca, and QT interval-prolonging medications on the risk of sudden cardiac arrest in a cohort of hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This case-control study among 43,200 hemodialysis patients occurred between 2002 and 2005; 510 patients who experienced a witnessed sudden cardiac arrest were compared with 1560 matched controls. This study examined covariate-adjusted sudden cardiac arrest risk associations with serum Ca, dialysate Ca, serum dialysate Ca gradient, and prescription of QT-prolonging medications using logistic regression techniques. RESULTS: Patients assigned to low Ca dialysate<2.5 mEq/L were more likely to be exposed to larger serum dialysate Ca gradient and had a greater fall in BP during dialysis treatment. After accounting for covariates and baseline differences, low Ca dialysate<2.5 mEq/L (odds ratio=2.00, 95% confidence interval=1.40-2.90), higher corrected serum Ca (odds ratio=1.10, 95% confidence interval=1.00-1.30), and increasing serum dialysate Ca gradient (odds ratio=1.40, 95% confidence interval=1.10-1.80) were associated with increased risk of sudden cardiac arrest, whereas there were no significant risk associations with QT-prolonging medications. CONCLUSIONS: Increased risk of sudden cardiac arrest associated with low Ca dialysate and large serum dialysate Ca gradients should be considered in determining the optimal dialysate Ca prescription.