Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study

Abstract

Introduction: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α₁-Microglobulin (α₁-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α₁-m and β₂-microglobulin (β₂-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. Methods: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α₁-m, β₂-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. Results: Clearance rates of α₁-m at 60 min were −2.8 ± 5.2 mL/min with Pre-PS, −0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α₁-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β₂-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. Conclusion: The removal rate of α₁-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β₂-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α₁-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.