Abstract
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 β2-microglobulin-related amyloids (Aβ2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating β2-microglobulin (β2M). 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 Aβ2M 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 β2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aβ2M 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 Aβ2M amyloidogenesis by reducing the amyloid-related proteins.
Acknowledgements
The authors thank Kaneka Co. for the technical assistance.
Author contributions
All authors contributed to the study’s conception, design, analysis and interpretation of data. The specific contributions are as follows: conception and study design: S.Y., F.G., Y.G., T.Y. and I.N.; sampling: S.Y., K.G., K.O., N.I., H.S., I.E. and R.A.; proteomic analysis: S.Y., Keiko Yamamoto (K.Y.1), Y.H. and M.S.; measurement of serum levels of proteins: S.Y., M.K. and M.D.; in vitro amyloid fibril formation: S.Y., Keiichi Yamaguchi (K.Y.2), K.N. and Y.G. Data interpretation: S.Y., S.G. and I.N.; manuscript drafting: S.Y., K.Y.1 and K.Y.2. Supervision and mentorship: Y.G., S.G., F.G., T.Y. and I.N. Each author contributed important intellectual content during the drafting or revision of the manuscript and takes responsibility for the overall work, ensuring that any questions regarding the accuracy or integrity of any part of the study are appropriately investigated and resolved.
Disclosure statement
This study was conducted via a collaboration between Niigata University and Kaneka Co. SY has received honoraria from Kyowa Kirin and research funding from Toray Medical Co., Ltd and Kaneka Co. The other authors declare no competing interests.
Data availability statement
Restrictions apply to the availability of the data analyzed in this study to preserve patient confidentiality. Data will be shared upon request to the corresponding author.