Supplementary Material for: Removal of α1-microglobulin using post-dilution online hemodiafiltration with polymethylmethacrylate membrane: an open-label, single-arm study

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. Alpha-1-microglobulin (α1-m), 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: The clearances 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 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%]. The adsorption clearance of β2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than in Pre-PS. Discussion/Conclusion: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. 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 poor nutritional state.