Strippoli, Giovanni FM

Abstract 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.

Abstract Background Pain is the highest prioritized patient-reported outcome in people with autosomal dominant polycystic kidney disease (ADPKD) but remains infrequently and inconsistently measured in clinical trials and poorly managed in clinical settings. A recently completed systematic review of pain in ADPKD identified 26 different outcome measures. None of these measures were considered appropriate as a core outcome measure due to the lack of patient-important dimensions, inadequate content, relatively long duration of completion time and limited evidence to support psychometric robustness. Methods We convened an international Standardized Outcomes in Nephrology–Polycystic Kidney Disease consensus workshop involving 21 patients/caregivers and 40 health professionals (clinicians, nurses, researchers, policy makers and industry representatives) from 18 countries to discuss the identification or development of a core outcome measure for pain. Results Four themes were identified highlighting fundamental issues for the measurement of pain in ADPKD: distressing and disrupting life participation; variability and ambiguity in defining pain; stigma, frustration and adaptation to pain; and ensuring validity and feasibility of pain measures. Conclusions Existing measures were found to be insufficient in capturing pain as a core outcome and there was consensus on the need for a new validated measure that is simple, succinct and addresses the impact of pain on life participation. This measure will facilitate the appropriate prioritization of pain in all trials and guide clinical decision making in people with ADPKD.