Why High-Volume Hemodiafiltration Should Be the New Standard in Dialysis Care: A Comprehensive Review of Clinical Outcomes and Mechanisms

The management of end-stage kidney disease (ESKD) poses a substantial clinical and economic challenge, characterized by a growing patient burden, rising healthcare costs, and persistent unmet needs to enhance survival outcomes and quality of life. Background/Objectives: Conventional high-flux hemodialysis (HD) remains the dominant form of renal replacement therapy for ESKD but is still associated with substantial morbidity and mortality. High-volume post-dilution online hemodiafiltration (HVHDF) offers a promising alternative by enhancing convective removal of uremic toxins. Methods: We conducted a narrative review of randomized controlled trials, meta-analyses, real-world cohort studies, and registry analyses published between 2010 and 2024. Evidence was categorized into short-term, medium-term, and long-term outcomes, including hemodynamic stability, inflammation, anemia, infection risk, cardiovascular events, cognitive decline, quality of life, and survival. Results: HVHDF improves short-term outcomes by enhancing toxin clearance, stabilizing blood pressure, reducing inflammation and oxidative stress, and improving anemia management. Medium-term benefits include improved nutritional status, reduced hospitalizations related to infections, and improved neurological and immune function. Long-term data from major trials (e.g., ESHOL, CONVINCE) and large real-world studies show consistent reductions in all-cause and cardiovascular mortality, particularly with convection volumes ≥23 L/session. A clear dose-response relationship supports the clinical relevance of convection volume targets. HVHDF has also shown benefits in preserving cognitive function and enhancing health-related quality of life. Conclusions: Strong and converging evidence supports HVHDF as a superior dialysis modality. Given its survival benefits, better tolerance, and broader impact on patient outcomes, HVHDF should be considered the new standard of care in dialysis, especially in light of the recent regulatory approval of the machine that provides the ability to perform HDF in the United States.