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High-dose hemodiafiltration improved survival compared with standard hemodialysis for patients with kidney failure resulting in the need for kidney-replacement therapy, according to the randomized CONVINCE trial.

High-dose hemodiafiltration cut all-cause mortality to 17.3% compared with 21.9% on conventional high-flux hemodialysis over a median 30 months of follow-up (HR 0.77, 95% CI 0.65-0.93), reported researchers led by Peter J. Blankestijn, MD, of University Medical Center Utrecht in the Netherlands.

These findings settle the concerns of confounding by indication in prior supportive evidence, the group suggested in the in conjunction with a presentation at the European Renal Association meeting in Milan.

Hemodiafiltration is a dialysis technique -- used largely in the ICU setting in the U.S. but more commonly in Europe and Japan -- for ultrafiltration by both diffusion and convection to boost removal of larger molecules while maintaining fluid balance by infusing sterile non-pyrogenic replacement fluid directly into the patient's blood.

Three prior randomized controlled trials were inconclusive on the survival benefits of hemodiafiltration versus standard hemodialysis, while a fourth showed a survival benefit with hemodiafiltration.

"However, concerns about attrition during follow-up in these trials were raised by observers in the scientific and nephrology communities," Blankestijn's group noted. Patient-level meta-analysis of the four trials also supported a survival benefit with hemodiafiltration when the convection dose was at least 23 L per session in post-dilution mode, but that was not a predefined analysis -- raising concerns of confounding by indication.

For the , Blankestijn and colleagues aimed to increase "the likelihood of an unbiased effect estimate through the trial design, which included complete follow-up of mortality, no data censoring after certain key events (e.g., renal transplantation), and competing-risk statistical analyses."

The trial included 1,360 adults with stage V kidney failure who had been treated with dialysis for at least 3 months. To eliminate the confounding by indication concerns, all participants had to be candidates for high-dose hemodiafiltration with a convection volume of at least 23 L in post-dilution mode per session and be willing to have dialysis three times a week.

Patients with a history of cardiovascular disease or diabetes had the same mortality risk, regardless of randomized treatment group, but hemodiafiltration reduced the likelihood of death during the median 30 months of follow-up by a relative 42% in those without a history of cardiovascular disease (HR 0.58, 95% CI 0.42-0.79) and by 35% among those without diabetes mellitus (HR 0.65, 95% CI 0.48-0.87).

Among the secondary outcomes, death from cardiovascular causes, recurrent hospitalization, and the composite outcome of fatal or nonfatal cardiovascular outcomes didn't differ between groups.

Hemodiafiltration, however, reduced infection-related death (HR 0.69, 95% CI 0.49-0.96), including COVID-19 deaths, as the trial was conducted from November 2018 through April 2021, during the first waves of the pandemic.

The researchers cautioned that drawing conclusions about reduced risk of COVID-19 mortality was "complicated because COVID-19 as a diagnosis was added during the course of the trial. We cannot make the distinction between death from COVID-19 and death from other causes (e.g., cardiovascular) in a patient with COVID-19."

The pandemic also reduced the sample size compared with what was planned due to difficulties in recruitment during lockdowns. Lower-than-expected mortality rates in the trial "can be partly attributed to selection by the treating physician to enroll patients who were likely to reach a convection volume of at least 23 liters during each session, an indication that these patients had relatively good vascular access," Blankestijn's group wrote, although not invalidating the mortality advantage of hemodiafiltration.

The largely European population studied might impact generalizability to patients who are not white, as could the potential that the inclusion criteria resulted in a healthier population than typical for hemodialysis patients in the U.S.

A pooled analysis of the trial findings with those of the prior trials could allow for more precise exploration of the benefits of hemodiafiltration in subgroups, the researchers noted.

Meanwhile, it's at least clear from all the trials that "the safety of hemodiafiltration was acceptable, provided that hygienic and microbiologic rules are fully respected," they concluded.

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