The Effect of Different Hemodialysis Modalities on Cardiovascular Events and Patients’ Outcomes: A Narrative Review

Abstract: Hemodialysis (HD) remains the cornerstone of renal replacement therapy for patients with End-Stage Kidney Disease (ESKD). Over the past two decades, conventional HD has been followed by more advanced dialysis modalities, including online hemodiafiltration (HDF) and expanded hemodialysis (HDx). These have been introduced to improve solute clearance and clinical outcomes. Yet cardiovascular events, mortality, and symptom burden remain unacceptably high, and it remains unclear which modality is optimal. Studies so far have shown that HDF, which combines diffusive and convective transport, is associated with lower all-cause and cardiovascular mortality than conventional HD. This is particularly the case when HDF achieves adequate convection volume and in patients with certain characteristics. HDx, which employs medium cut-off membranes, enables the clearance of larger middle molecules and may reduce inflammation, hospitalization, and symptom burden, data on hard cardiovascular and survival endpoints remain limited. Across modalities, studies assessing quality of life, symptom relief, and treatment tolerability are few and often underpowered, leaving important patient priorities underexplored. In parallel, the implementation of resourceintensive modalities such as HDF raises concerns about water, energy, and plastic use. This underscores the need for overall environmental sustainability in a growing dialysis population. Current evidence supports an individualized, outcome-driven approach to prescribing HD, HDF, and HDx, balancing potential cardiovascular and survival advantages of high-volume HDF and HDx against feasibility, cost, and environmental impact. This narrative review synthesizes evidence from randomized controlled trials and large observational cohorts comparing conventional low- and high-flux HD with post-dilution HDF and HDx, highlighting key clinical and methodological controversies.