High-Volume Hemodiafiltration: Expanding the Evidence Beyond Randomized Trials – A Critical Perspective on the 2025 EuDial Consensus

The 2025 EuDial Consensus systematically compared hemodiafiltration (HDF) to high-flux hemodialysis (HD), highlighting HDF's superior removal of middle-molecular-weight uremic toxins, potential survival advantages, and immunomodulatory properties. High-volume HDF (HV-HDF), defined by a substitution volume exceeding 23 L per session, was associated with improved cardiovascular outcomes, reduced infection-related mortality, and decreased systemic inflammation. Background/Objectives: Nevertheless, the consensus refrains from endorsing HDF as the standard of care, citing insufficient evidence to prevent sudden cardiac death, reduce intradialytic hypotension, or significantly lower hospitalization rates compared to HD. Methods: This review critically evaluates the EuDial Consensus, highlighting its methodological strengths while noting potential limitations stemming from an exclusive reliance on randomized controlled trials (RCTs). The exclusion of real-world evidence (RWE) and mechanistic studies may have led to an underestimation of HDF's broader clinical benefits, particularly in cardiovascular stability, inflammation control, and anemia management. Results: Multiple studies have demonstrated HDF’s capacity to enhance immune function, improve erythropoiesis, and increase clearance of beta-2 microglobulin (β2M) and other pro-inflammatory toxins. Furthermore, the CONVINCE trial’s economic analysis supports HDF’s cost-effectiveness, especially when considering improved survival and reduced dependency on erythropoiesis-stimulating agents. Conclusions: Future research should integrate RWE and mechanistic insights to define better HDF’s therapeutic potential, particularly concerning anemia control, infection mitigation, and hemodynamic stability. While the EuDial Consensus provides valuable clinical guidance, its conclusions should be contextualized within a broader and evolving evidence base. Given its multidimensional benefits, post-dilution High-Volume HDF is increasingly viewed as a preferred renal replacement therapy modality, warranting wider clinical practice adoption.