In-center hemodialysis six times per week versus three times per week

Abstract

Background: 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.

Methods: Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey. Secondary outcomes included cognitive performance; self-reported depression; laboratory markers of nutrition, mineral metabolism, and anemia; blood pressure; and rates of hospitalization and of interventions related to vascular access.

Results: Patients in the frequent-hemodialysis group averaged 5.2 sessions per week; the weekly standard Kt/V(urea) (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) was significantly higher in the frequent-hemodialysis group than in the conventional-hemodialysis group (3.54±0.56 vs. 2.49±0.27). Frequent hemodialysis was associated with significant benefits with respect to both coprimary composite outcomes (hazard ratio for death or increase in left ventricular mass, 0.61; 95% confidence interval [CI], 0.46 to 0.82; hazard ratio for death or a decrease in the physical-health composite score, 0.70; 95% CI, 0.53 to 0.92). Patients randomly assigned to frequent hemodialysis were more likely to undergo interventions related to vascular access than were patients assigned to conventional hemodialysis (hazard ratio, 1.71; 95% CI, 1.08 to 2.73). Frequent hemodialysis was associated with improved control of hypertension and hyperphosphatemia. There were no significant effects of frequent hemodialysis on cognitive performance, self-reported depression, serum albumin concentration, or use of erythropoiesis-stimulating agents.

Conclusions: Frequent hemodialysis, as compared with conventional hemodialysis, was associated with favorable results with respect to the composite outcomes of death or change in left ventricular mass and death or change in a physical-health composite score but prompted more frequent interventions related to vascular access. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT00264758.).

Figure 1. Coprimary Composite Outcomes and Main Secondary Outcomes

Kaplan–Meier curves are shown for the composite outcomes of death or change in left ventricular (LV) mass (Panel A) and death or change in the physical-health composite (PHC) score from the RAND 36-item health survey (Panel B). For each value for the coprimary composite outcome on the horizontal axis, the Kaplan–Meier curve indicates the proportion of patients in the respective treatment groups with an equal or more favorable outcome. The horizontal distance between the Kaplan–Meier curves at the 50% value on the vertical axes indicates the median composite outcome results. Median outcomes for the composite outcome of death or change in LV mass correspond to a reduction in LV mass of 12.3 g in the frequent-hemodialysis group, as compared with a reduction of 2.2 g in the conventional-dialysis group (difference in medians, 10.1 g). The greater separation in the two curves on the right side of the graph of the change in LV mass is because nine patients had reductions in LV mass of at least 60 g; all of them were in the frequent-hemodialysis group. The median results for the composite outcome of death or change in physical-health composite score correspond to an increase in the physical-health composite score of 2 points in the frequent-hemodialysis group as compared with no change in the conventional-dialysis group (difference in medians, 2 points). Changes in LV mass ranged from a decrease of 51.2 g to an increase of 68.8 g in the conventional-dialysis group and from a decrease of 174.5 g to an increase of 61.9 g in the frequent-hemodialysis group. Changes in the physical-health composite score ranged from a decrease of 27 points to an increase of 22 points in conventional-dialysis group, and from a decrease of 28 points to an increase of 29 points in the frequent-hemodialysis group. The standardized effect sizes for the main secondary outcomes (Panel C) were calculated as follows: the mean differences in LV mass, physical-health composite score (in which higher scores indicate better physical health), Beck Depression Inventory score (in which higher scores indicate more severe depression), albumin concentration before dialysis, phosphorus concentration before dialysis, and systolic blood pressure before dialysis were divided by the baseline standard deviation; the mean difference in log dose of erythropoiesis-stimulating agent (ESA) was divided by the standard deviation of the log baseline ESA dose; the log risk ratio for failure to complete the Trail Making Test Part B was divided by square root ([1 – p]/p), where p is the fraction of participants who did not complete the test within 5 minutes at baseline; the log hazard ratio for hospitalization unrelated to vascular access or death was divided by square root (1/p), where p is the fraction of patients with a hospitalization unrelated to vascular access or death. ESA doses of less than 5000 erythropoietin equivalent units were set to 5000 before log transformation.