In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation.

Background and objectives: Vascular access standards are predominantly based on older, single-center reports; however, the hemodialysis population has changed dramatically and primary arteriovenous fistula failure is a huge problem. This prospective, multicenter study used standardized definitions to analyze patency rates and potential risk factors that affect functional patency and late arteriovenous fistula functionality. Design, setting, participants, & measurements: Eleven centers participated in a guidelines implementation program. All new permanent vascular accesses were included. Patency and functional patency, defined as access survival from creation and from first dialysis use, respectively, were calculated using Kaplan-Meier analysis. Risk factors for primary functional patency loss (intervention-free interval) and secondary failure (abandonment) were determined using regression models. Results: A total of 491 arteriovenous fistulas were placed in 395 patients. Six-, 12-, and 18-mo secondary patency and functional patency were 75 ± 2.0, 70 ± 2.3, and 67 ± 2.7% and 90 ± 1.9, 88 ± 2.2, and 86 ± 2.7%, respectively. Primary failure rate was 40%. Thrombosis rate was 0.14 per patient-year. Diabetes and arteriovenous fistula surveillance were significantly associated with primary functional patency loss. Preoperative duplex was inversely related to secondary failure. The secondary failure rate per hospital varied from 0 to 39%. Conclusions: This study showed a marked difference between patency and functional patency, likely to be explained by high primary failure rates. Hemodialysis patients with diabetes can be expected to have reduced primary functional patency rates, but if treated adequately, then arteriovenous fistula functionality can be maintained as long as in patients without diabetes.

Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. After a median follow-up of 2.5 years (Q1–Q3: 1.9–3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m² body surface area (BSA) per session], with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.

Summary: Background and objectives: There is increasing awareness that residual renal function (RRF) has beneficial effects in hemodialysis (HD) patients. The aim of this study was to investigate the role of RRF, expressed as GFR, in phosphate and anemia management in chronic HD patients. Design, setting, participants, & measurements: Baseline data of 552 consecutive patients from the Convective Transport Study (CONTRAST) were analyzed. Patients with a urinary output ≥100 ml/24 h (n = 295) were categorized in tertiles on the basis of degree of GFR and compared with anuric patients (i.e., urinary output 4.13 ml/min per 1.73 m²), as compared with 46% in anuric patients despite lower prescription of phosphate-binding agents. Mean hemoglobin levels were 11.9 ± 1.2 g/dl with no differences between the GFR categories. The ESA index was 31% lower in patients in the upper tertile as compared with anuric patients. After adjustments for patient characteristics, patients in the upper tertile had significantly lower serum phosphate levels and ESA index as compared with anuric patients. Conclusions: This study suggests a strong relation between RRF and improved phosphate and anemia control in HD patients. Efforts to preserve RRF in HD patients could improve outcomes and should be encouraged.

Randomized trials of catheter-based renal denervation (RDN) as therapy for resistant hypertension showed conflicting results in blood pressure (BP) lowering effect. Adherence to medication is modest in this patient group and may importantly drive these conflicting results. SYMPATHY is a prospective open label multicenter trial in Dutch patients with resistant hypertension. Primary outcome was change in daytime systolic ambulatory BP at 6 months. Patients were randomly assigned to RDN on top of usual care. Adherence to BP lowering drugs was assessed at baseline and follow-up, using blood samples drawn synchronously with BP measurements. Patients and physicians were unaware of the adherence assessment. Primary analyses showed a mean difference between RDN (n=95) and control (n=44) in changes in daytime systolic ambulatory BP after 6 months of 2.0 mm Hg (95% confidence interval, −6.1 to 10.2 mm Hg) in favor of control. In 80% of patients, fewer medications were detected than prescribed and adherence changed during follow-up in 31%. In those with stable adherence during follow-up, mean difference between RDN and control for daytime systolic ambulatory BP was −3.3 mm Hg (−13.7 to 7.2 mm Hg) in favor of RDN. RDN as therapy for resistant hypertension was not superior to usual care. Objective assessment of medication use shows that medication adherence is extremely poor, when patients are unaware of monitoring. Changes over time in adherence are common and affect treatment estimates considerably. Objective measurement of medication adherence during follow-up is strongly recommended in randomized trials. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850901.