Beyond Kt/V: Redefining Dialysis Adequacy as Targeted Cardiovascular Risk Reduction
Carmine Zoccali, Giovanni Strippoli, Francesco Locatelli, Francesca Mallamaci, Len Usyat, Stefano StuardAbstract
Background
Cardiovascular 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.
Aim
This 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 synthesis
Randomized 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.
Conclusions
Future 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.