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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/Vurea, 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.

In a multicenter, randomized trial, 2776 patients undergoing maintenance hemodialysis who were not currently taking a statin were randomly assigned to rosuvastatin or placebo. At a median of 3.8 years of follow-up, rates of the composite primary end point of death from cardiovascular causes, myocardial infarction, or stroke did not differ significantly between the two study groups. Patients undergoing maintenance hemodialysis were randomly assigned to rosuvastatin or placebo. At a median of 3.8 years of follow-up, rates of the composite primary end point of death from cardiovascular causes, myocardial infarction, or stroke did not differ significantly between the two study groups. Patients undergoing maintenance hemodialysis have a greatly increased risk of premature cardiovascular disease. 1 , 2 However, the pattern of cardiovascular disease in such patients differs from that in the general population, and although the risk of myocardial infarction is increased, other cardiovascular events, such as sudden cardiac death and heart failure, predominate. 1 – 3 Moreover, the relationship between cardiovascular disease and conventional risk factors is inconsistent, inverse, or U-shaped. 1 , 2 , 4 Since low-density lipoprotein (LDL) cholesterol levels may be low or normal in patients with advanced renal disease, there is particular uncertainty regarding the use of lipid-lowering therapy. 1 , 2 , 4 , 5 Statin . . .

ObjectivesA prospective randomised trial to compare two different durations of maintenance immunosuppressive therapy for the prevention of relapse in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV).MethodsPatients with AAV were recruited 18–24 months after diagnosis if they were in stable remission after cyclophosphamide/prednisolone-based induction followed by azathioprine/prednisolone maintenance therapy. They were randomised (1:1) to receive continued azathioprine/prednisolone to 48 months from diagnosis (continuation group) or to withdraw azathioprine/prednisolone by 24 months (withdrawal group). The primary endpoint was the relapse risk, from randomisation to 48 months from diagnosis.ResultsOne hundred and seventeen patients were randomised and 110 remained to the trial end. At entry, median serum creatinine was 116 μmol/L (range 58–372), 53% were ANCA positive. The percentage of patients presenting with relapse was higher in the withdrawal than in the continuation treatment group (63% vs 22%, p<0.0001, OR 5.96, 95% CI 2.58 to 13.77). ANCA positivity at randomisation was associated with relapse risk (51% vs 29%, p=0.017, OR 2.57, 95% CI 1.16 to 5.68). Renal function, ANCA specificity, vasculitis type and age were not predictive of relapse. Severe adverse events were more frequent in the continuation than withdrawal groups (nine vs three events), but the continuation group had better renal outcome (0 vs 4 cases of end-stage renal disease), with no difference in patient survival.ConclusionsProlonged remission maintenance therapy with azathioprine/prednisolone, beyond 24 months after diagnosis reduces relapse risk out to 48 months and improves renal survival in AAV.Trial registration numberISRCTN13739474

Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (−15.3 to 34.6) in patients treated with HDF and increased by 11.9% (−15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

This study assessed the relationship between initial responsiveness to darbepoetin alfa and outcomes in patients with chronic kidney disease and type 2 diabetes mellitus. A poor initial hematopoietic response was associated with an increased risk of death or cardiovascular events. Erythropoiesis-stimulating agents (ESAs) have been credited with a reduced need for red-cell transfusion and improved quality of life for patients with end-stage kidney disease who have severe anemia. 1 In patients with chronic kidney disease who do not require dialysis and have moderate anemia, the use of ESAs remains substantial, despite little evidence of benefit and increased concern that these agents may confer harm. 2 – 4 Trials comparing lower and higher hemoglobin targets have been interpreted to suggest that targeting of a lower hemoglobin range would be a safer approach in these patients, 2 , 5 , 6 leading to recommendations for continued use of . . .

Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Patients with advanced CKD (blood creatinine ≥1.7 mg/dL [≥ 150 μmol/L] in men or ≥1.5 mg/dL [ ≥ 130 μmol/L] in women) with no known history of myocardial infarction or coronary revascularization were randomized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily (with the latter arm rerandomized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo). The key outcome will be major atherosclerotic events, defined as the combination of myocardial infarction, coronary death, ischemic stroke, or any revascularization procedure. A total of 9,438 CKD patients were randomized, of whom 3,056 were on dialysis. Mean age was 61 years, two thirds were male, one fifth had diabetes mellitus, and one sixth had vascular disease. Compared with either placebo or simvastatin alone, allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy, hepatic toxicity, or biliary complications during the first year of follow-up. Compared with placebo, allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL (1.10 mmol/L) at 1 year and 33 mg/dL (0.85 mmol/L) at 2.5 years. Follow-up is scheduled to continue until August 2010, when all patients will have been followed for at least 4 years. SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD.

Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants. Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase. These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.

This study aimed to investigate the effects of different dialysis modalities on cognitive function in patients with end stage renal disease and to explore their association with the clearance of protein bound uremic toxins. A total of 135 patients undergoing maintenance hemodialysis were enrolled and randomly assigned to one of three treatment groups hemodialysis HD hemodialysis combined with hemodiafiltration HD + HDF and hemodialysis combined with hemodiafiltration plus hemoperfusion HD + HDF + HP. Cognitive function was evaluated using the Mini Mental State Examination MMSE and the Montreal Cognitive Assessment MoCA which assess multiple domains including memory attention executive function and orientation. Plasma levels of homocysteine Hcy and indoxyl sulfate IS were measured before and after dialysis sessions. Statistical analysis included comparisons among groups Spearman correlation multiple linear and logistic regression and receiver operating characteristic ROC curve analysis. Cognitive scores improved progressively across the three groups with the greatest improvement observed in the HD + HDF + HP group. Toxin levels decreased accordingly and were lowest in the HD + HDF + HP group. Multivariate analysis identified Hcy and IS as independent risk factors for cognitive impairment. ROC analysis demonstrated that both toxins had strong predictive value for cognitive decline. The results indicate that combined HDF and HP enhances removal of protein bound toxins and is associated with better preservation of cognitive function. These findings suggest that triple modality dialysis may provide a promising strategy to reduce cognitive decline and improve neurological outcomes in patients undergoing maintenance hemodialysis.

Online hemodiafiltration (Ol-HDF) and expanded hemodialysis (HDx; using medium cut-off dialyzers) have shown superior removal of diverse uremic toxins, particularly middle molecules and inflammatory cytokines, compared to conventional hemodialysis (HD). However, the relative efficacy of toxin removal between HDx and Ol-HDF remains unclear. This study aimed to compare these two techniques. A randomized controlled trial was conducted among thrice-weekly hemodialysis patients. Participants were randomized into either a post-dilution Ol-HDF group or an HDx group using two types of medium cut-off dialyzers (Theranova 500 ® and Elisio HX21 ® ) over 8 weeks. Efficacy was assessed by reduction ratios (RR) and pre-dialysis toxin levels. Statistical analysis used T-tests and generalized estimating equations. A total of 40 patients were enrolled (mean age 64.6 ± 12.0 years; 82.5% male; dialysis vintage 53.4 ± 38.0 months). The Ol-HDF group, with a mean convection volume of 24.7 L, had significantly higher RR for beta-2 microglobulin (82.8% vs. 74.6%; p  < 0.001), parathyroid hormone (80.4% vs. 60.6%; p  = 0.007), homocysteine (58.0% vs. 50.0%; p  = 0.009), and kappa- and lambda-free light chains (73.3% vs. 64.6%; p  = 0.0001 and 62.5% vs. 52.0%; p  = 0.0026, respectively). Pre-dialysis toxin levels at the end of the study were similar between groups. These findings highlight that Ol-HDF demonstrated superior removal of uremic toxins, while HDx was comparable to Ol-HDF in maintaining pre-dialysis levels of middle molecules and inflammatory cytokines. Trial registration This study was registered in the Thai Clinical Trials Registry (TCTR) on the first posted date 10/02/2023 with the registration number TCTR20230210004.