New Dialysis Techniques

Abstract

Introduction and Aims: The Frequent Hemodialysis Network Nocturnal trial randomized 87 subjects to 6 times per week home nocturnal hemodialysis (FNHD) or to 3 times per week hemodialysis (3HD) for 1 year. Subjects were subsequently free to modify their treatment schedule. We describe effects of randomized treatment assignment on mortality over a median follow-up of 3.7 years. Methods: We obtained dates of death and kidney transplantation through July 2011 using linkage to USRDS and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment. Results: For randomized subjects (FNHD vs. 3HD), 62% vs. 0%, 51% vs. 27%, and 52% vs. 33% received frequent long hemodialysis (≥27 hours of dialysis over ≥4.5 treatments per week) during the trial, the first year after the trial, and subsequently. There were 14 deaths in the FNHD arm and 5 deaths in the 3HD arm overall; during the first year after the trial there were 9 deaths in the FNHD arm and 1 death in the 3HD arm. The overall mortality hazard ratio for randomization to FNHD vs. 3HD was 3.88, (95% CI: 1.27 to 11.79), p = 0.01. The 19 deaths in the two treatment groups included 9 deaths related to cardiac causes, 2 to infection, and 1 to the dialysis procedure itself (unrecognized central venous catheter disconnection at night in a subject randomized to FNHD). Three deaths, all in the conventional group, were due to cancer. The finding of higher mortality for patients randomized to FNHD compared to 3HD was observed consistently for all-cause mortality over the entire follow-up (14 vs. 5 deaths), all-cause mortality censoring transplants (14 deaths vs. 4 deaths), cardiac or infectious deaths (9 vs. 2 deaths), and deaths of all causes excluding cancer (14 vs. 2 deaths).Pre-specified subgroups were tested for interaction with mortality, including age, sex, race, Canadian vs. U.S. center, experienced vs. inexperienced center, ESRD vintage, or baseline left ventricular mass; none approached statistical significance. The trend toward higher mortality in the FNHD group was particularly marked among patients with ≤ 500 ml/day of urine volume at baseline. Vascular access events did not appear to predict mortality: in the FNHD group, 12 post-trial deaths in 43 subjects were evenly distributed among those with and those without vascular access events during the randomized trial phase.The results of as-treated analyses relating mortality to a patient's exposure to frequent long hemodialysis (≥27 hours/week and ≥4.5 treatments/week) over the previous 12 months was 3.06 (95% CI 1.11 to 8.43, p = 0.03) and over the previous 6 months was 1.12 (95% CI: 0.44 to 3.22, p = 0.74). The attenuation of the as-treated hazard ratio reflected the reclassification of 3 deaths from the frequent long category using the 12 month running average to the non-frequent long category using the six month moving average. Conclusions: Our observation of higher mortality among subjects randomized to FNHD compared to 3HD raises concerns regard...

The Use of a Multidimensional Measure of Dialysis Adequacy—Moving beyond Small Solute Kinetics

“…With the development of more efficient dialyzers in the 1980s and the increased focus on reduction of urea, a small, readily dialyzable solute, as the indicator of dialysis adequacy, the typical dialysis session length decreased from 6-8 to 2.5-4 hours (28). More recently, several large observational studies have found an association between longer dialysis session duration and lower mortality risk (29)(30)(31); however, reduced mortality with longer dialysis time is not evident in all such analyses (32), and an effect of dialysis time on mortality has not yet been established in a sufficiently powered randomized trial. Increased dialysis time may have contributed to the benefit of daily dialysis on the important surrogate outcome, left ventricular mass index (LVMI): in the Frequent Hemodialysis Network (FHN) Trial, the total weekly time was greater with dialysis 6 times/ wk than with 3 times/wk, but the relative contributions of increased solute clearance and lower ultrafiltration rate resulting from increased dialysis time is not known (25).…”