Online hemodiafiltration for kidney failure: guidance and best clinical practice recommendations from the Italian Society of Nephrology
Giovanni F M Strippoli, Giovanni Pellegrino, Jörgen Hegbrant, Paolo Fabbrini, Paolo Luca Maria Lentini, Filippo Aucella, Vincenzo Panichi, Maurizio Gallieni, Bernard Canaud, Andrew Davenport, Alberto Ortiz, Rosa Ramos, Jolanta Malyszko, Rümeyza Kazancıoğlu, Martin Kuhlman, Ana Carina Ferreira, Krister Cromm, Sagar Nigwekar, Allen R Nissenson, Luca De NicolaAbstract
Background
Online hemodiafiltration (HDF) enhances the removal of middle molecules, including large-middle molecules, through the combined action of diffusion and convection. Randomized controlled trials (RCTs) and individual participant data (IPD) meta-analyses demonstrate improved cardiovascular outcomes and, importantly, a reduction in all-cause mortality when HDF is delivered with sufficiently high convective volumes in post-dilution mode. These findings underscore that an adequate convective dose is a critical determinant of clinical benefits compared to high-flux hemodialysis (HD). However, translation into consistent clinical practice remains heterogeneous. Therefore, the Italian Society of Nephrology convened an international, multidisciplinary panel to synthesize randomized evidence comparing online post-dilution HDF with high-flux HD in adults receiving maintenance hemodialysis.
Methods
The critical outcomes included all-cause and cardiovascular mortality, whereas the important outcomes included selected patient-reported health domains, including physical function, patient-perceived cognitive function, pain interference, social participation, and health-related quality of life. The certainty of the evidence was appraised using the GRADE methodology. Structured guidance recommendations and best practice statements were developed through a consensus. Sensitivity analyses were performed to assess the robustness of the observed mortality effect.
Results
High-volume post-dilution HDF reduces all-cause mortality (hazard ratio 0.84; 95% CI 0 74–0.95; moderate-certainty evidence) and cardiovascular mortality (hazard ratio 0.78, 95% CI 0.64–0.96; moderate-certainty evidence; data from an individual participant data analysis of trials of high volume HDF versus high-flux HD). Emerging evidence suggests slower deterioration in selected patient-reported domains, including physical function, patient-perceived cognitive function, pain interference, and social participation (low-certainty evidence). Safety with on-line post-dilution HDF has been demonstrated to be similar to that of high-flux HD.
Conclusions
Online post-dilution HDF should be regarded as a dose-dependent therapy. We recommend its use to reduce cardiovascular mortality and suggest high-volume HDF to reduce all-cause mortality and slow deterioration in selected patient-reported health domains. Effective implementation in clinical practice requires a targeted and individualized approach with careful optimization and monitoring of convective volume, along with appropriate treatment time, blood-flow rate, supporting infrastructure, and consideration of patient preferences. This guidance provides evidence-based recommendations and best practice statements for its use.