Among patients in the Frequent Hemodialysis Network (FHN) Nocturnal Trial, those assigned to frequent nocturnal hemodialysis had higher mortality rates than those assigned to conventional dialysis. That was the primary finding of a post-trial observational study conducted by Michael V. Rocco, MD, MSCE, and colleagues and reported in the American Journal of Kidney Diseases [2015;66(3):459-468].
The FHN Nocturnal Trial was designed to assess the safety and efficacy of nocturnal hemodialysis six times a week compared with conventional home hemodialysis three times a week on intermediate outcomes. The trial was not powered for comparisons of mortality between treatment groups; however, mortality was a specified secondary outcome for descriptive purposes. The current report reflected data on the mortality analysis during extended follow-up of the FHN Nocturnal Trial.
The FHN Nocturnal Trial was a multicenter, randomized clinical trial in which 87 patients were randomly assigned in a 1:1 ratio to receive either six times weekly nocturnal hemodialysis (nocturnal hemodialysis) or three times weekly hemodialysis (conventional hemodialysis). Patients were enrolled in March 2006 and follow-up continued until May 2010. At the end of the 1-year trial period, patients were allowed to modify their dialysis regimens according to their preferences as agreed to by their attending physician.
Additional data (prospective and retrospective) could be collected from consenting participants. The extended follow-up data were collected from April 2010 through April 2011 when surviving participants had reached their 13th to 57th month of follow-up.
Of the 87 enrolled patients, 83 remained in follow-up at the end of the 12-month randomized trial phase, including six who had received a kidney transplant. Fifty-two patients consented to linkage with the United States Renal Data System; for those patients, extended follow-up data on mortality and transplantation was obtained through July 31, 2011. Mortality and transplantation data on the remaining 31 patients were obtained from the institutional review boards of the individual clinical sites; mortality and transplantation status were ascertained for those patients during the summer of 2012. The researchers used log-rank tests and Cox regression to relate mortality to the initial randomization assignment.
Median follow-up for the trial and post-trial observation period was 3.7 years. During that time, there were two deaths in the nocturnal arm (12-month trial period) and an additional 12 deaths during the post-trial period in the nocturnal hemodialysis arm. In the conventional arm, there was one death during the 12-month trial period and four during the post-trial period. Nine of the frequent nocturnal deaths occurred during the first year after the randomized trial ended. Twenty-one individuals had undergone transplantation, three without transplants were lost to follow-up, and 44 were confirmed alive without transplants.
In the primary intent-to-treat analysis that included the full follow-up period, the overall mortality hazard ratio (HR) in the nocturnal arm was 3.88 (95% confidence interval [CI], 1.27-11.79; P=.01). None of the 14 deaths in the nocturnal group and one of the five deaths in the conventional group occurred after transplantation. Hence, censoring for transplantation increased the relative HR for mortality for those assigned to the nocturnal group to 5.98 (95% CI, 1.71-20.92; P=.002).
The mortality rate differential between randomized arms was not affected by the prespecified subgroups of age, sex, race, US versus Canadian center, experienced versus inexperienced center, end-stage renal disease vintage, baseline left ventricular mass, or baseline urine volumes. Cause of death in the two treatment groups included nine deaths related to cardiac causes, two to infection, and one to the dialysis procedure itself. Three deaths (all in the conventional arm) were due to cancer.
Five post-trial deaths in the nocturnal arm were recorded among 22 participants without vascular access events during the trial phase and seven were recorded among 21 participants with access events. In the conventional arm, four post-trial deaths occurred among 26 participants with no access events; no events occurred among 15 participants with access events during the randomized trial phase. None of the deaths was clearly related to a vascular access event.
For purposes of the as-treated analyses, a frequent and long schedule was defined as the combination of >4.5 hemodialysis sessions per week and a weekly dialysis time >27 hours. Sixty-one percent of participants in the nocturnal group met both of these criteria for frequent long dialysis compared with 0% in the conventional group during the trial period; 51% versus 27% during the first year post trial; and 52% versus 33% subsequently.
Using as-treated analysis with a 12-month running treatment average, ten of 13 deaths in the nocturnal group occurred in participants who had been following a frequent-long schedule. No deaths occurred in conventional group participants who decided, after the trial ended, to move to a frequent-long schedule.
The HR for mortality was 3.06 (95% CI, 1.11-8.43; P=.03). Six-month running treatment data showed an HR of 1.19 (95% CI, 0.44-3.21; P=.7). Attenuation of the as-treated HR reflected the reclassification of three deaths from the frequent-long category using the 12-month running average to the non–frequent-long category using the 6-month moving average. There was no significant association between mortality and the number of treatments per week or weekly treatment time when averaged over either the prior 6 months or the prior 12 months when these variables were analyzed as continuous variables.
“In summary, our observation of higher mortality among individuals randomly assigned to the nocturnal hemodialysis group compared to the conventional hemodialysis group raises concerns regarding the long-term effects of frequent nocturnal hemodialysis, but should be interpreted cautiously due to a surprisingly low (0.03 per patient-year) mortality for individuals randomly assigned to the conventional group, low statistical power for the mortality comparison, and the high rate of hemodialysis prescription changes,” the researchers said.
- There are few available data on the long-term mortality rate for patients who receive nocturnal home hemodialysis.
- Researchers analyzed data from the Frequent Hemodialysis Network Nocturnal Trial to assess long-term mortality rates during an extended follow-up of that trial.
- Patients in the nocturnal group had a higher mortality rate compared with those in the conventional hemodialysis group.