Proteomic profiling of arteriovenous fistula tissue identifies dysregulated oxidoreductase proteins in diabetic end-stage renal disease.

BACKGROUND: Diabetes mellitus is a leading cause of end-stage renal disease (ESRD), with up to 35% of patients with diabetes mellitus developing kidney disease. This study aims to monitor protein expression changes in ESRD patients with and without type 2 diabetes mellitus (T2DM). METHODS: A total of 186 ESRD patients who underwent arteriovenous fistula creation surgery were enrolled in this study. Of these, 148 patients were classified into the T2DM (n = 73) and non-T2DM (n = 75) groups. Data-independent acquisition proteomic analysis was conducted to analyze differentially expressed proteins. Enzyme-linked immunosorbent assay kits, immunohistochemical staining, Western blotting were employed to validate the differently expressed proteins within the cohort. RESULTS: Proteomic analysis identified 26 upregulated and 15 downregulated proteins in the T2DM group compared with the non-T2DM group. The serum concentrations of 4-hydroxynonenal, malondialdehyde, and glutathione were elevated in the T2DM group. The immunohistochemical staining index for GPX4 and xCT was lower, while α-SMA, IL-6, TNF-α, and TGF-β levels were higher in the T2DM group compared with the non-T2DM group. Western blotting indicated the downregulation of SOD1 and GPX4 as well as upregulation of PTGS2 and ACLS4 in the T2DM group accompanied by increased levels of Fe(2+), total iron, and Fe(3+). CONCLUSION: This study underscores oxidoreductase activity-related proteins, including ferroptosis-related proteins to be differentially expressed in ESRD combined with T2DM.