Background: Patients undergoing maintenance hemodialysis (HD) exhibit increased levels of uremic toxins, which are associated with poor outcomes. Recently, new dialysis membranes have allowed clearance of solutes with higher molecular weight, without significant albumin losses high-retention-onset-HD (HRO-HD). Methods: Prospective crossover trial, in which 16 prevalent patients switched from high-flux HD (HF-HD) to online hemodiafiltration (olHDF) and HRO-HD for 4 weeks. The following variables were evaluated: pre- and post-dialysis serum concentrations of albumin, urea, phosphate (P), beta-2 microglobulin (β2M), and total mass (TM) extraction and dialyzer clearance of urea, P, and β2M. Results: Comparing HF-HD, olHDF, and HRO-HD, respectively, there were no differences regarding pre-dialysis serum concentrations of albumin (3.94 ± 0.36, 4.06 ± 0.22, and 3.93 ± 0.41 g/dL, p = 0.495), urea (166 ± 29, 167 ± 30, and 164 ± 27 mg/dL, p = 0.971), P (4.9 ± 2.1, 5.2 ± 1.6, and 4.9 ± 2.1 mg/dL, p = 0.879), and β2M (31.3 ± 7.1, 32.6 ± 8.6, and 33.7 ± 5.9 µg/mL, p = 0.646). β2M clearance was significantly lower in HF-HD in comparison to both olHDF and HRO-HD: 43 (37–53) versus 64 (48–85) mL/min, p = 0.013, and 69 (58–86) mL/min, p = 0.015, respectively. Post-dialysis β2M serum concentration was higher in HF-HD in comparison to olHDF and HRO-HD: 11.6 (9.6–12.4) vs. 5.7 (4.5–7.0) µg/mL, p = 0.001, and 5.6 (5.3–7.6) µg/mL, p = 0.001, respectively. TM extraction of urea, P, and β2M were similar across the 3 dialysis modalities. Conclusions: olHDF and HRO-HD were superior to HF-HD regarding β2M clearance, leading to lower post-dialysis β2M levels.
