International Journal of Molecular and Cellular Medicine (IJMCM)

End-stage renal disease (ESRD), the most advanced stage of chronic kidney disease, is a major diabetes-related complication associated with severe metabolic and oxidative disturbances. Ferroptosis, an iron-dependent form of regulated cell death, may contribute to diabetic kidney disease (DKD) progression; however, its role in ESRD remains unclear.  This case-control study investigated oxidative stress markers and ferroptosis-related gene expression in ESRD patients secondary to DKD and healthy controls. Biochemical parameters, oxidative stress markers, and the mRNA expression of tumor suppressor genes (p21 and p53) and nuclear factor erythroid 2-related factor 2 (Nrf2) were assessed in peripheral blood mononuclear cells. Group comparisons were performed using appropriate statistical tests, and logistic regression was used to evaluate the relationship between ESRD status. ESRD patients showed significantly higher Nrf2 expression (P < 0.0001) and lower p53 expression (P = 0.026), while p21 expression did not differ significantly (P = 0.32). Catalase activity and malondialdehyde levels were significantly increased in ESRD (P = 0.0001), whereas glutathione peroxidase activity was decreased (P = 0.018). Logistic regression demonstrated significant associations between ESRD and CAT activity (OR = 1.082), MDA levels (OR = 3.627), GPx activity (OR = 0.985), Nrf2 expression (OR = 2.133), and p53 expression (OR = 0.711) (all P < 0.05). These findings suggest that ESRD secondary to DKD is associated with significant alterations in oxidative stress status and changes in the expression of genes linked to ferroptosis-related pathways, providing indirect evidence of their possible involvement