High-Volume Hemodiafiltration Remains the Benchmark for Survival Evidence in Dialysis

At the recent European Renal Association (ERA) Congress in Glasgow, researchers presented updated results from the Spanish MOTheR study.¹

While the study adds information to a growing body of dialysis research, high-volume hemodiafiltration (HvHDF, achieving convection volume of at least 23 liters) remains an advanced dialysis therapy supported by large multinational randomized studies showing the most significant reduction in the risk of mortality for people receiving dialysis.

Key Takeaways:

High-volume hemodiafiltration (HvHDF) remains the only advanced dialysis therapy supported by large multinational randomized evidence demonstrating a statistically significant reduction in all-cause mortality.
The MOTheR study was designed to determine whether treatment with a medium cut-off dialyzer was not more than 25% worse for a composite endpoint of all-cause mortality or various cardiovascular events compared to online hemodiafiltration (OL-HDF) ̶ a type of study known as a non-inferiority trial.
This study, limited to a single country, had multiple unplanned interim analyses. Less than 30 percent of the originally enrolled patients had complete follow-up to the end of the study.
While the study met its primary endpoint using a broad combined measure of either death or non-fatal cardiovascular events, the confidence intervals were broad, meaning there remains substantial uncertainty around the results.
And importantly, the study failed to show non-inferiority for mortality when analyzed independently.
MOTheR should therefore not be interpreted as demonstrating statistical equivalent or comparable mortality outcomes between Theranova medium cut-off dialyzers and OL-HDF.
Treatment decisions should continue to be guided by the totality of evidence, including multinational randomized trials, long-term real-world experience, and the ability to consistently deliver and monitor therapy in routine clinical practice.

Understanding What MOTheR Demonstrated

MOTheR was a randomized study conducted in a single country comparing treatment with a medium cut-off dialyzer and online hemodiafiltration (OL-HDF).

The study met its primary objective using a broad combined measure of either mortality or non-fatal cardiovascular events, that may not be equally meaningful for patients and their families.

And importantly, the study failed to demonstrate comparable results for mortality when mortality was examined on its own.

Mortality remains one of the most important outcomes for patients receiving dialysis and is therefore a critical consideration when interpreting the findings.

Results Should Be Interpreted in the Context of the Study Design

As with any non-inferiority study, findings should be interpreted within the context of how the study was designed.

Important considerations include:

the use of a broad combined endpoint rather than mortality alone
the wide 25% non-inferiority margin
non-inferiority does not imply equivalence
the modest number of patients (262) on the MCO arm, with multiple unplanned interim analyses, and less than 30 percent of all analyzed patients completing follow-up to the end of the study
conducted within a single country that may not reflect broader dialysis populations
the uncertainty reflected by the wide confidence intervals around key outcomes

The study was substantially smaller than landmark outcome trials evaluating high-volume hemodiafiltration and was not designed to demonstrate either equivalence or superiority.

These factors are critically important when considering how broadly the findings can be applied and what conclusions can reasonably be drawn about treatment outcomes.

High-Volume Hemodiafiltration Is Supported by the Strongest Clinical Evidence

High-volume hemodiafiltration is the advanced extracorporeal dialysis therapy supported by a large multinational randomized controlled trial demonstrating the most statistically significant reduction in the risk of mortality.

The ground-breaking CONVINCE² trial, published in the New England Journal of Medicine, demonstrated a 23% reduction in all-cause mortality using a single, clinically meaningful endpoint focused on mortality. In addition, more than two decades of real-world experience across more than 90 countries and tens of thousands of patients have demonstrated HvHDF is associated with improvements in mortality, hospitalization rates³, and patient-reported outcomes.⁴

By contrast, MOTheR did not demonstrate comparable results for mortality and therefore does not provide the same level of evidence supporting mortality outcomes.

Dr Bernard Canaud, Emeritus Professor of Nephrology at the Montpellier University School of Medicine, commented: “As clinicians, we must not confuse what the study demonstrated and what it did not: MOTheR met a broad composite endpoint, but it did not establish non-inferiority for mortality, which remains one of the most important measures of treatment benefit in dialysis.”

Supporting Physician Choice Through Evidence-Based Care

Patients and physicians benefit from having multiple treatment options available.

Fresenius Medical Care supports individualized treatment decisions based on patient needs, local practice requirements, and the strength of available clinical evidence.

The best treatment decisions are made when physicians understand not only the available technologies, but also the quality and strength of the evidence supporting each option.

HvHDF uniquely provides a measurable and prescribable convective dose, allowing treatment delivery to be monitored, standardized, and optimized in routine clinical practice.

We are excited about the rollout of the HvHDF therapy to benefit dialysis patients around the world, including the 5008X CAREsystem in the U.S.

De Sequera P, et al. MOTheR HDx study: A multicentre, open-label, prospective, randomized study to explore the morbidity and mortality in patients dialyzed with the Theranova HDx in comparison to online hemodiafiltration. Presented at: ERA Congress; June 3–6, 2026; Glasgow, Scotland.
Blankestijn PJ, Vernooij RWM, Hockham C, Strippoli GFM, Canaud B, Hegbrant J, Barth C, Covic A, Cromm K, Cucui A, Davenport A, Rose M, Török M, Woodward M, Bots ML; CONVINCE Scientific Committee Investigators. Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure. N Engl J Med. 2023 Aug 24;389(8):700-709. doi: 10.1056/NEJMoa2304820
Zhang Y, Winter A, Ficociello LH, Ferrera BA, Carioni P, Apel C, Arkossy O, Anger M, Kossmann R, Usvyat LA, Stuard S. Real-World Hospitalization Outcomes with On-Line Hemodiafiltration Versus High-Flux Hemodialysis: A Retrospective, International Cohort Study. Clin J Am Soc Nephrol. 2025 Dec 23;21(5):852–9. doi: 10.2215/CJN.0000000955
Rose M, Fischer FH, Liegl G, Strippoli GFM, Hockham C, Vernooij RWM, Barth C, Canaud B, Covic A, Cromm K, Cucui AM, Davenport A, Fischer KI, Hegbrant J, Jaha H, Schappert A, Török M, Woodward M, Bots ML, Blankestijn PJ; CONVINCE Scientific Committee and CONVINCE Investigators. The CONVINCE randomized trial found positive effects on quality of life for patients with chronic kidney disease treated with hemodiafiltration. Kidney Int. 2024 Nov;106(5):961-971. doi: 10.1016/j.kint.2024.07.014