Introduction: Online hemodiafiltration (OL-HDF) and hemodialysis (HD) using high-performance membranes such as adsorptive, medium cut-off (MCO), and super high-flux (SHF) dialyzers have been implemented to enhance the removal of middle molecules (MM). The aim of this study was to compare the efficacy of different dialysis strategies and dialyzers on small solutes and MM reduction ratio (RR) and mass removal. Methods: We performed a prospective study in 8 HD patients. Each patient underwent 9 dialysis sessions: seven sessions on HD using either Theranova 500™, Elisio 21H™, Renak PS-2.0W™, Filtryzer BK-2.1F™, Vie 21X™, TS-2.1UL™ or FDY 210-GW™ dialyzers and two sessions on OL-HDF using Elisio 21H™ or Renak PS-2.0W™ dialyzers. Results: Urea mass removal and RR were similar between all dialysis strategies. The lowest beta2-microglobulin RR was achieved with Filtryzer BK-2.1F™ HD (p < 0.05). Compared to Elisio 21H™ HD, Renak PS-2.0W™ OL-HDF produced higher beta2-microglobulin mass removal (181 ± 46 vs. 317 ± 161 mg, p < 0.05). Theranova 500™ HD, Vie 21X™ HD, FDY 210-GW™ HD, Elisio 21H™ OL-HDF, and Renak PS-2.0W™ OL-HDF induced higher RR for kappa and lambda FLC, as compared to Elisio 21H™ HD and Filtryzer BK-2.1F™ HD (p < 0.05). Renak PS-2.0W™ OL-HDF achieved higher kappa FLC mass removal compared to Elisio 21H™ HD (563 ± 515 vs. 141 ± 47 mg, p < 0.01) and to Renak PS-2.0W™ HD (563 ± 515 vs. 153 ± 25 mg, p < 0.05). Albumin loss varied from 0.02 ± 0.05 to 7.6 ± 3.8 g/session with Elisio 21H™ HD and Renak PS-2.0W™ OL-HDF, respectively. Compared to all other strategies, Renak PS-2.0W™ OL-HDF induced a significantly higher albumin loss (p < 0.05). Conclusion: This study confirms that albumin loss and removal of MM are similar using conventional Elisio 21H™ OL-HDF, MCO-HD, and SHF type V dialyzers. Although Renak PS-2.0W™ OL-HDF provides high performance for MM depuration, this protein-permeable dialyzer should not be used in OL-HDF because of excessive albumin loss.

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