Long-Term Effects of Frequent In-Center Hemodialysis

Abstract

The Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in-center hemodialysis sessions per week for 12 months. As reported previously, frequent in-center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self-reported physical health. Here, we determined the long-term effects of the 12-month frequent in-center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%-90% range, 1.5-5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self-reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post-trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in-center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.

Keywords: clinical trial; end-stage renal disease; hemodialysis.

Figure 1.

CONSORT diagram. Disposition of Study Subjects. Consolidated Standards of Reporting Trials diagram. HD, hemodialysis.

Figure 2.

Kaplan-Meier curves depicting survival of patients randomized to the frequent and conventional hemodialysis groups. (A) Displays the survival curves including follow-up after transplantation; (B) displays the survival curves with follow-up censored at transplantation. The relative hazards were computed using Cox proportional hazards regression. HR, hazard ratio.

Figure 3.

Posterior distributions of the relative hazard comparing mortality during extended follow-up among patients randomized to frequent and conventional hemodialysis under prior distributions representing neutral (A) and optimistic (B) perspectives on the probability of a treatment benefit. The posterior distributions characterize the implications of the observed relative hazard of 0.54 (downward pointing arrow) for individuals with the perspectives indicated by the conservative and enthusiastic priors before observing the results. The posterior probabilities of harm (black region), a small benefit with relative hazard between 0.8 and 1 (gray region), and a substantial benefit with relative hazard ≤0.8 are 0.07, 0.32, and 0.61, respectively, under the neutral prior and 0.02, 0.11, and 0.87, respectively, under the optimistic prior.