en Clinical Biochemistry Clinical Biochemistry Original Article Original Article <p style="text-align: justify;"><span style="font-size:12px;"><span style="font-family:Tahoma;"><span style="line-height:107%">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.&nbsp; 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 <i>(p21 </i>and<i> p53)</i> and nuclear factor erythroid 2-related factor 2 (<i>Nrf2)</i> 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 <i>Nrf2</i> expression (P < 0.0001) and lower <i>p53</i> expression (P = 0.026), while <i>p21</i> 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), <i>Nrf2</i> expression (OR = 2.133), and <i>p53</i> 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</span></span></span></p> End-stage renal disease, Diabetic kidney disease, Ferroptosis, Gene expression, Oxidative stress 1356 1367 http://ijmcmed.org/browse.php?a_code=A-10-8477-3&slc_lang=en&sid=1 Shaker Ghalioun Ebrh shakeralhdedi12345@gmail.com 100319475328460038276 0009-0006-9153-4594 No Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Gholamreza Dehghan dehghan2001d@yahoo.com 100319475328460038277 100319475328460038277 Yes Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran Hamid Tayebi Khosroshahi khosroshahiht@gmail.com 100319475328460038278 100319475328460038278 No Department of Nephrology, Tabriz University of Medical Sciences, Tabriz, Iran Mohammad Khalaj Kondori khalaj49@gmail.com 100319475328460038279 100319475328460038279 No Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran