Hemodiafiltration Offers Survival Benefit in Patients With Kidney Failure

The incidence of kidney failure is increasing worldwide. Patients with kidney failure are commonly treated with hemodiafiltration or hemodialysis. While practice differences across the globe may favor one method over the other, hemodialysis is used more often overall.

There have been four randomized, controlled trials examining possible survival benefits associated with hemodiafiltration versus hemodialysis. Of those four trials, three were inconclusive and the fourth demonstrated a survival benefit for hemodiafiltration. Results of a meta-analysis of individual patient data from the four trials indicated a survival benefit with hemodiafiltration when a convection volume was delivered at a high dose, with a putative threshold of at least 23 liters per session in postdilution mode.

Due to the inconsistency and limitations of the previously published studies, Peter J. Blankestijin, MD, and colleagues conducted a pragmatic, multinational, randomized, controlled trial among patients with kidney failure who had received high-flux hemodialysis for at least 3 months. Results were reported online in the New England Journal of Medicine.

The primary outcome of interest was death from any cause. Secondary outcomes included cause-specific mortality, composite fatal and nonfatal cardiovascualr events, kidney transplantation, and recurrent hospitalizations for any cause and for causes related to infection. Cardiovascular events were defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary procedure, therapeutic carotid procedure, and vascular intervention or peripheral limb amputation.

The trial intervention was high-dose hemodiafiltration with on-line production of substitution fluid and ultrapure bicarbonate-based dialysis fluid at a convection volume of at least 23 liters per session in postdilution mode. The comparison group received conventional hemodialysis by means of high-flux dialysis membranes and ultrapure bicarbonate-based dialysis fluid.

Cox proportional-hazards models were used to estimate hazard ratios (HR) and corresponding 95% CIs for the primary and key secondary outcomes involving single events. The Anderson-Gill model was applied for recurrent outcomes of hospitalizations for any cause and for cause-specific reasons. Both models included the trial site as a random effect. Competing risk analyses with kidney transplantation as the competing event were conducted for the primary outcomes.

Trial enrollment occurred from November 2018 through April 2021. A total of 1360 patients underwent randomization in a 1:1 ratio to receive either high-dose hemodiafiltration or continuation of high-flux hemodialysis; 683 patients were assigned to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. At baseline, the two groups were well balanced in demographics, coexisting illnesses, laboratory values, and medications. Median follow-up was 30 months for both groups. Loss to follow-up occurred in 18 patients in the hemodiafiltration group and in 12 patients in the hemodialysis group.

The target volume of at least 23 liters per session for high-dose convection was achieved in 92% of delivered hemodiafiltration sessions. The mean convection volume among the patients was stable during the study period. The Kt/V value (K is urea clearance by the dialyzer, t is treatment time, and V is urea distribution volume) was higher in the hemodiafiltration group than in the hemodialysis group and remained higher during the study period.

The primary outcome of death from any cause occurred in 17.3% of patients (n=118) in the hemodiafiltration group (7.13 events per 100 patient-years) compared with 21.9% of patients (n=148) in the hemodialysis group (9.19 events per 100 patient-years) (HR, 0.77; 95% CI, 0.65-0.93; P=.005). Of the 266 deaths, 25.6% (n=68) were attributed to cardiovascular disease, 9.8% (n=26) to COVID-19, and 21.1% (n=56) to other infections.

Among patients with a history of cardiovascualr disease at baseline, the risk of death was similar in the two study groups (HR, 0.99; 95% CI, 0.76-1.28). Among patients with no history of cardiovascular disease at baseline, the risk of death was lower in the hemodiafiltration group (HR, 0.58; 95% CI, 0.42-0.79). Among patients with diabetes mellitus, the risk of death was similar in the two groups (HR, 0.97; 95% CI, 0.72-1.31). Among patients without diabetes mellitus, the risk of death was lower in the hemodiafiltration group compared with the hemodialysis group (HR, 0.65; 95% CI, 0.48-0.87).

The two groups were similar in the risk of death from cardiovascualr causes (HR, 0.81; 95% CI, 0.49-1.33) and the composite outcome of fatal or nonfatal cardiovascualr outcomes (HR, 1.07; 95% CI, 0.86-1.33). For infection-related death, including death from COVID-19, there was an apparent reduction in favor of the high-dose hemodiafiltration group (HR, 0.69; 95% CI, 0.49-0.96).

The two groups were similar in the risks of recurrent hospitalization, including for nonfatal hospitalization (HR, 1.11 (95% CI, 0.98-1.25), hospitalization for infection including COVID-19 infection (HR, 1.06; 95% CI, 0.86-1.30), and hospitalization for infection that excluded COVID-19 (HR, 0.97; 95% CI, 0.74-1.26).

Limitations to the study findings cited by the authors included the sample size being smaller than anticipated due to the COVID-19 pandemic that limited participant recruitment, and the overall risk of death being lower than that used for determine the sample size.

In summary, the researchers said “In our trial, at a median follow-up of 30 months after randomization, patients with kidney failure who received high-dose hemodiafiltration had a lower risk of death than those who received conventional high-flux hemodialysis.”

Takeaway Points

1. Researchers reported results of a multinational, randomized, controlled trial to determine whether high-dose hemodiafiltration offers survival benefits compared with hemodialysis in a population of patients with kidney failure.
2. Patients were randomized in a 1:1 ratio to receive either high-dose hemodiafiltration or to continue conventional high-flux hemodialysis.
3. Patients in the hemodiafiltration group had a lower risk of death from any cause compared with patients in the conventional hemodialysis group.

Source: New England Journal of Medicine