Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis

Background: Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of beta 2-microglobulin-related amyloids (A beta 2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating beta 2-microglobulin (beta 2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis. Methods: We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on A beta 2M amyloid fibril formation in vitro. Results: We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as beta 2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the A beta 2M amyloid fibril formation. Conclusions: HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting A beta 2M amyloidogenesis by reducing the amyloid-related proteins.