Carmine Zoccali, Giovanni Strippoli, Francesco Locatelli, Francesca Mallamaci, Len Usyat, Stefano Stuard

CONCLUSIONSFuture trials should be multicenter, phenotype-enriched, mechanism-specific, adequately powered, and endpoint-adjudicated. Endpoints should match the intervention: rhythm monitoring for potassium strategies, cardiac magnetic resonance and objective volume assessment for sodium or volume interventions, and integrated inflammatory, nutritional, vascular, and clinical outcomes for membrane-based approaches.AIMThis narrative review examines dialysis strategies intended to mitigate cardiovascular stress arising from cyclic volume loading, rapid ultrafiltration, electrolyte shifts, myocardial stunning, vascular stiffness, inflammation and anemia, middle-molecule toxicity, loss of residual kidney function, and the long interdialytic interval.EVIDENCE SYNTHESISRandomized trials and individual-patient-data meta-analyses have evaluated high-dose online hemodiafiltration, with some studies reporting improved survival compared with conventional hemodialysis. Results have varied across trials, and questions remain regarding treatment delivery, generalizability and the mechanisms underlying the observed effects. More frequent, nocturnal, and long-duration dialysis schedules improve intermediate endpoints, including left ventricular mass, blood pressure, phosphate control, ultrafiltration intensity, and treatment tolerance, but hard-outcome evidence remains limited. Expanded hemodialysis with medium cut-off membranes improves clearance of larger middle molecules, although cardiovascular benefit is unproven. Individualized dialysate potassium and sodium prescriptions are physiologically compelling precision-dialysis approaches targeting arrhythmia risk, volume overload, blood pressure, and cardiac remodeling, but definitive endpoint trials are needed. Incremental dialysis might preserve residual kidney function in selected incident patients, but cardiovascular benefit remains vulnerable to selection bias.BACKGROUNDCardiovascular disease remains the leading cause of death in patients receiving maintenance dialysis, whereas conventional thrice-weekly hemodialysis was developed primarily around small-solute clearance rather than cardiovascular protection.

Peter J Blankestijn, Sanne Roos, Claudia Barth, Michiel L Bots, Krister Cromm, Andrew Davenport, Jörgen Hegbrant, Giovanni Strippoli, Robin W M Vernooij, Bernard Canaud

Hemodiafiltration (HDF) with online production of substitution fluid has emerged as kidney replacement therapy and is increasingly adopted worldwide. Recent randomized controlled trials, individual participant data meta-analyses, and large real-world studies have demonstrated that high-volume HDF improves clinical outcomes compared with conventional high-flux hemodialysis (HD), including reduction in all-cause mortality and hospitalization. Importantly, these benefits appear dose-dependent, with achieved convective volume serving as a modifiable treatment target. Beyond survival, data suggest advantages in patient reported outcomes and evidence for cost-effectiveness. This review provides a practical overview of contemporary HDF delivery, focusing on the prescription variables that determine treatment performance, including vascular access, blood flow rate, filtration fraction, treatment time, dialyzer characteristics, and machine technology. Current evidence suggests that high-volume post-dilution HDF can be achieved safely and reproducibly in routine clinical practice using standard thrice-weekly treatment schedules and contemporary dialysis platforms. Monitoring should extend beyond conventional small-solute clearance metrics to include indicators of middle-molecule removal and patient-centered outcomes. Future developments are expected to move HDF from a uniform prescription strategy towards a more individualized approach. Emerging data support refinement of convection-volume targets according to patient characteristics and treatment response, while incorporation of patient-reported outcomes and predictive models may facilitate precision-based therapy. Advances in automation, digital monitoring, biosensors, and artificial intelligence are most likely to further optimize treatment delivery and personalization. Although implementation requires investment in infrastructure, training, and quality assurance, growing evidence suggests that these costs may be offset by improved clinical outcomes, reduced healthcare utilization, and enhanced sustainability. Collectively, current evidence supports high-volume HDF as among the most effective dialysis modality currently available and it is likely to become the global standard for kidney replacement therapy.