Hemodiafiltration versus High-Flux Hemodialysis and Risk of Mortality: A Multinational Target Trial Emulation

Randomized trials suggested that hemodiafiltration improved survival over high-flux hemodialysis, but real-world evidence is limited. Target trial emulation showed that hemodiafiltration was associated with lower mortality than high-flux hemodialysis. The findings supported broader use of hemodiafiltration when technically feasible and clinically appropriate.

Randomized trials suggest that high-volume postdilution hemodiafiltration (HDF) may improve survival compared with high-flux hemodialysis, but evidence from routine clinical practice and from regions underrepresented in trials remains limited.

We emulated a target trial comparing HDF with high-flux hemodialysis using data from European Clinical Database, a multinational registry of dialysis patients treated in 8 European countries. Adults receiving thrice-weekly in-center dialysis between 2014 and 2019 were eligible. Follow-up began 91 days after dialysis initiation. Sustained treatment strategies were defined as receipt of the assigned modality for at least 90% of sessions. Inverse probability weighting was used to emulate randomized treatment assignment. The primary outcome was all-cause mortality, with kidney transplantation treated as a competing event.

Among 19,539 eligible patients at day 91, inverse probability weighting created a weighted pseudopopulation of 19,758 patients (8641 HDF; 11,117 hemodialysis). During a median follow-up of 16 months (interquartile range, 6-32), 4282 deaths occurred. HDF was associated with a lower risk of all-cause mortality compared with high-flux hemodialysis (hazard ratio, 0.72; 95% confidence interval, 0.67 to 0.77). At 2 years, the weighted cumulative incidence of death was 20.6% in the HDF group and 22.3% in the hemodialysis group, corresponding to an absolute risk reduction of 1.7% points. The results were consistent across sensitivity analyses, including analyses accounting for country, competing risks, informative censoring, protocol adherence, and an intention-to-treat-like exposure definition. The association was broadly similar across prespecified subgroups, with only a stronger relative benefit observed among patients with preexisting cardiovascular disease (interaction P < 0.001). Higher delivered convective volumes were associated with better survival; however, these findings should be interpreted cautiously because higher convective volumes may reflect patient stability and center expertise rather than a causal dose-response relationship.

In this large multinational target trial emulation, sustained high-volume postdilution HDF was associated with lower mortality than high-flux hemodialysis.