Solute clearances and fluid removal in the frequent hemodialysis network trials

Abstract

Background: The Frequent Hemodialysis Network (FHN) is conducting 2 randomized clinical trials, a daytime in-center trial ("daily") comparing 6 versus 3 treatments/wk, and a home nocturnal trial comparing 6 nocturnal treatments versus 3 conventional treatments/wk. The goal of this study was to project separation between the treatment and control arms of these studies for measures of dialysis dose by using simulations based on 2-compartment variable-volume models.

Setting & participants: Data from the most recent hemodialysis treatment in 100 patients dialyzed 3 times/wk at facilities of the Renal Research Institute in New York and from 2 data sets (n = 154 and 115 patients) from the Hemodialysis (HEMO) trial.

Design: Observational study.

Predictor: Dialysis prescriptions for the treatment and control arms in the FHN trials. DIALYSIS REGIMEN OUTCOMES: Treatment time, ultrafiltration rate, standard Kt/V/wk for urea (stdKt/V(urea)), and continuous clearance estimates based on ratios of urea, creatinine, and normalized beta(2)-microglobulin generation rates (denoted by Gn) to time-averaged concentrations (TACs) of these solutes during 1 treatment week.

Results: The expected differences between median values in the experimental and control groups were weekly treatment time: daily trial, 29%; nocturnal trial, 234%; ultrafiltration rate: daily, -20%; nocturnal, -69%; stdKt/V(urea): daily, 52%; nocturnal, 133%; Gn(urea)/TAC(urea): daily, 34%; nocturnal, 130%; Gn(cr)/TAC(cr): daily, 31%; nocturnal, 135%; and Gn(beta2)/TAC(beta2): daily, 8%; nocturnal, 67%.

Limitations: Use of simulated data and assumption of equivalent volumes and ultrafiltration rates between treatment arms.

Conclusions: The nocturnal 6-times-weekly regimen produces substantially greater separation between the treatment and control arms than the daytime 6-times-weekly regimen for a wide range of treatment parameters. However, the 6-times-weekly interventions in both FHN trials will produce substantially greater separation than in the HEMO trial, where separations in median weekly treatment time and stdKt/V(urea) between the 3-times-weekly high- and standard-dose groups were 18% and 17%, respectively. The FHN trials will test whether substantial increases in solute clearance and other effects of frequent hemodialysis materially influence selected intermediate outcome measures.

Trial registration: ClinicalTrials.gov NCT00264758 NCT00271999.