High-Volume Online Hemodiafiltration: Does Patient Phenotype Matter?

Online hemodiafiltration (OL-HDF) has been associated with improved clinical outcomes compared with conventional hemodialysis in randomized trials, particularly in studies achieving high convection volumes. Whether specific patient phenotypes derive greater benefit from OL-HDF remains uncertain. This narrative review examines the available evidence regarding potential clinical phenotypes associated with enhanced benefit from high-volume OL-HDF, including older adults, anuric patients, individuals with heart failure, patients with poor intradialytic hemodynamic tolerance, frail patients, those with increased inflammatory burden, and incident dialysis patients. Current randomized evidence has not detected convincing treatment-effect modification across the clinical subgroups examined; however, most subgroup analyses were not designed or powered to establish equivalence of treatment effects. Higher achieved convection volumes have been associated with improved outcomes, although these observational or post-randomization associations should not be interpreted as proof of a causal dose–response relationship. Nevertheless, several high-risk clinical scenarios may be associated with greater absolute clinical benefit because of an elevated baseline risk of adverse outcomes. Available data suggest that personalization of OL-HDF should focus less on selecting eligible phenotypes and more on optimizing treatment delivery according to patient characteristics, treatment goals, and technical feasibility. Future research should explore patient-centred outcomes and identify strategies to maximize the benefits of high-volume OL-HDF within a precision medicine framework.