Kidney Week

Abstract: FR-OR28

Mass Spectrometry-Based Proteomic Analysis of Adsorbed Molecules in a Hexadecyl-Immobilized Cellulose Beads Column for the Treatment of Dialysis-Related Amyloidosis

Session Information

• Dialysis: Outcomes and Achievements
  November 05, 2021 | Location: Simulive, Virtual Only
  Abstract Time: 04:30 PM - 06:00 PM

Category: Dialysis

• 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

• Yamamoto, Suguru, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Suguru Yamamoto, MD, PhD

• Yamamoto, Keiko, Biofluid Biomarker Center, Niigata University, Niigata, Japan

Keiko Yamamoto,

• Hirao, Yoshitoshi, Biofluid Biomarker Center, Niigata University, Niigata, Japan

Yoshitoshi Hirao,

• Goto, Shin, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Shin Goto,

• Yamamoto, Tadashi, Biofluid Biomarker Center, Niigata University, Niigata, Japan

Tadashi Yamamoto,

• Gejyo, Fumitake, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan

Fumitake Gejyo,

• Narita, Ichiei, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

Ichiei Narita,

Background

Dialysis-related amyloidosis (DRA) is a serious complication in CKD patients undergoing long-term hemodialysis (HD). β₂-microglobulin (β₂-m)-related amyloid deposition induces osteoarticular disorders including carpal tunnel syndrome. Direct hemoperfusion with a column containing hexadecyl-immobilized cellulose beads (HICB) is used to adsorb circulating β₂-m to inhibit the progression of DRA. As use of the column improves joint pain and physical functions; it is possible that the column adsorbs not only β₂-m but also other molecules associated with amyloidogenesis and inflammation.

Methods

We included 14 HD patients with DRA. Proteins were extracted from the HICB-containing column after treatment and identified using liquid chromatography-linked mass chromatography. We measured the adsorption rate of the proteins detected by proteomics, and compared it with those in the patients undergoing HD and hemodiafiltration (HDF). The amyloid tissue deposition in the carpal tunnel in the HD patients (n = 8) was corrected using laser microdissection and examined on liquid chromatography-linked mass chromatography. The protein profiles were compared between the HICB-containing column and the amyloid lesions.

Results

With high confidence criteria, 200 proteins adsorbed by the HICB were identified (e.g., β₂-m SIN, 193.8 ± 143.4; lysozyme SIN, 156.5 ± 47.8). After passing the HICB-containing column, the serum levels of several proteins were decreased as compared with those in the HD dialyzer and HDF hemofilter (e.g., adsorption rate of β₂-m, 80.5 ± 9.8% vs 38.0 ± 25.5% [HD] and 25.0 ± 14.6% [HDF], p < 0.01; lysozyme, 79.2 ± 10.9% vs 15.8 ± 18.8% [HD] and 10.0 ± 13.4% [HDF], p < 0.01). In the amyloid deposited in the carpal tunnel, 143 proteins were identified, of which 54 were also found in the HICB-containing column. Cellular protein metabolic process was one of major Gene Ontology pathways in the common proteins (p = 1.05E-10).

Conclusion

The HICB-containing column adsorbed various proteins in the HD patients with DRA, of which some were found in the lesions with amyloid deposition. The results suggest that direct hemoperfusion with the HICB-containing column contributes to the improvement of DRA by reducing the levels of related proteins.

Funding

• Commercial Support – Kaneka Medix Co