On-Line High-Volume Hemodiafiltration: Current Evidence and Clinical Outcomes.

Despite continuous technological advances in dialysis therapy, patients with kidney failure undergoing maintenance hemodialysis continue to experience high morbidity and mortality, largely driven by cardiovascular disease and chronic inflammation. Conventional hemodialysis efficiently removes small solutes but has limited capacity to eliminate middle molecules and protein-bound uremic toxins that contribute to cardiovascular complications. On-line hemodiafiltration (OL-HDF) combines diffusive and convective transport, improving the clearance of a wider range of uremic toxins. Beyond its effects on solute removal, OL-HDF has been associated with improvements in several intermediate clinical outcomes, including better control of mineral metabolism, reduced inflammation, improved endothelial function, reduces the risk of intradialytic hypotension, and probable benefits in anemia management, nutritional status, and patient-reported quality of life. Over the past 3 decades, clinical research has evolved from mechanistic studies to randomized controlled trials and large-scale observational analyses evaluating hard clinical outcomes. Secondary analyses of clinical studies consistently identify convective volume as the effective "dose" of OL-HDF, demonstrating survival benefits when it exceeds 23 L per session. This chapter reviews the current clinical evidence on OL-HDF, including randomized trials, pooled analyses, real-world data, and translational outcomes, and discusses how treatment delivery and convective dose influence the clinical effectiveness of this modality.