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Hemodiafiltration versus High-flux Hemodialysis and Risk of Mortality: A Multinational Target Trial Emulation
Giovanni F M Strippoli1,2, Giovanni Tripepi3, Bernard Canaud4
1Department of Precision and Regenerative Medicine and Jonian Area (Dimepre-J), University of Bari, Italy.
Journal of the American Society of Nephrology : JASN
|August 13, 2026
Summary
High-volume post-dilution hemodiafiltration (HDF) is linked to better survival than high-flux hemodialysis (HD) in real-world practice. This study found HDF associated with a reduced risk of all-cause mortality in dialysis patients.
Area of Science:
- Nephrology
- Clinical Epidemiology
- Renal Replacement Therapy
Background:
- Randomized trials suggest high-volume post-dilution hemodiafiltration (HDF) may improve survival over high-flux hemodialysis (HD).
- Limited evidence exists from routine clinical practice, especially from underrepresented regions.
- Need for real-world data to validate HDF's survival benefits.
Purpose of the Study:
- To emulate a target trial comparing HDF with high-flux HD using multinational registry data.
- To assess the association between HDF and all-cause mortality in a large, diverse dialysis population.
- To investigate survival outcomes in routine clinical practice settings.
Main Methods:
- Emulated target trial using data from the EuCliD® multinational registry (2014-2019).
- Included adults receiving thrice-weekly in-center dialysis, with follow-up starting 91 days post-initiation.
- Used inverse probability weighting to emulate randomized assignment; primary outcome was all-cause mortality, with kidney transplantation as a competing risk.
Main Results:
- Hemodiafiltration (HDF) was associated with a significantly lower risk of all-cause mortality compared to high-flux hemodialysis (HD) (HR 0.72; 95% CI 0.67-0.77).
- At 2 years, weighted cumulative incidence of death was 20.6% for HDF vs. 22.3% for HD, an absolute risk reduction of 1.7 percentage points.
- Results were consistent across sensitivity analyses and broadly similar across subgroups, with a stronger benefit noted in patients with pre-existing cardiovascular disease.
Conclusions:
- Sustained high-volume post-dilution hemodiafiltration is associated with reduced mortality compared to high-flux hemodialysis in a large, multinational real-world setting.
- Findings support the use of HDF for improving survival outcomes in dialysis patients.
- Further research is needed to clarify the dose-response relationship between convective volumes and survival benefits.
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