The reduction of the dismally high mortality of current end-stage renal disease patients maintained on conventional standard haemodialysis (HD) remains an unmet medical need. Online haemodiafiltration (HDF) modes with various sites of fluid substitution (post-, pre-, mixed- and mid-dilution) are increasingly used worldwide as promising alternatives to conventional HD. Large scale cohort studies, post hoc analyses of randomized trials, and individual participant meta-analyses suggest that post-dilution and pre-dilution, especially with high substitution volumes, improve outcomes compared with conventional standard HD. However, there is no definitive proof of a survival advantage of HDF over standard HD. The different modes of high-volume HDF should be considered a therapeutic platform allowing to personalize and tailor routine HDF treatment. The selection of the HDF mode should be made according to individual patient characteristics. Utilizing high retention onset membranes, expanded haemodialysis (HDx) can achieve the same solute removal performance as HDF. Subgroups of high-volume OL-HDF patients could benefit from HDx. Ongoing and future trials should provide definitive proof for the superiority of high-volume OL-HDF over conventional HD or HDx to give guidance for the most favourable mode of dialytic therapy for clinical use.
Keywords: End-stage renal disease; Expanded haemodialysis; Haemodiafiltration; Survival.