The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Abstract

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

Trial registration: ClinicalTrials.gov NCT00271999.

Figure 1. FHN Nocturnal Trial patient flow

FHN, Frequent Hemodialysis Network; GFR, glomerular filtration rate; LV, left ventricular; MRI, magnetic resonance imaging; PHC, physical health composite.

Figure 2. Separation in treatment parameters between groups

Shown are distributions of the number of dialysis treatments per week (left), weekly treatment time in hours (center), and weekly standard Kt/V_urea (right) for the conventional (top) and frequent nocturnal (bottom) treatment groups. Each quantity was first averaged over the follow-up period separately for each patient. See Table 2 for means and s.d.s.

Figure 3. Mortality/LV mass composite and mortality/PHC composite results

Kaplan–Meier curves (conventional arm, black; frequent nocturnal arm, red) for the (a) death/LV mass composite and the (b) death/PHC composite. For any given value of the composite outcome indicated on the horizontal axis (time of death on the left, change in either LV mass or PHC among survivors on the right), the Kaplan–Meier curves indicate 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 axis indicates the median composite outcome results. CI, confidence interval; HR, hazard ratio; LV, left ventricular; PHC, physical health composite.

Figure 4. Histogram of change in left ventricular (LV) mass and physical health composite (PHC)

Shown are distributions of the change in LV mass (n = 76, a) and PHC (n = 77, b) in the nocturnal and conventional arms of the trial. Change in PHC summary includes one additional patient whose final PHC score occurred in the 8th month of follow-up whose PHC was censored in the primary PHC composite time-to-event analysis.

Figure 5. Main secondary results

The calculation of the standardized effect sizes is described in ref. . BP, blood pressure; CI, confidence interval; ESA, erythropoiesis-stimulating agent; HR, hazard ratio; LV, left ventricular.

Figure 6. Time to first vascular access event

Shown are Kaplan–Meier curves representing the conventional therapy (black) and the frequent nocturnal (red) groups for the time from randomization to each patient’s first access event, defined as an access failure or other access procedure. CI, confidence interval; HR, hazard ratio.