Diabetic Nephropathy and Oxidative Stress

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide and represents a major complication of diabetes mellitus. Increasing evidence implicates oxidative stress (OS) as a central driver in the initiation and progression of DN through complex molecular and cellular mechanisms. This narrative review systematically synthesizes published literature on OS in DN. Relevant studies were identified through electronic databases, including PubMed, Scopus, and Web of Science, focusing on molecular pathways, biomarkers, and therapeutic strategies. Data were qualitatively analyzed and integrated to provide a comprehensive overview. OS in DN is primarily driven by hyperglycemia-induced overproduction of reactive oxygen species via mitochondrial dysfunction, NADPH oxidase (NOX) activation, and accumulation of advanced glycation end-products. Key signaling pathways, including nuclear factor kappa B, nuclear factor erythroid 2-related factor 2 (Nrf2), and transforming growth factor-beta/Smad, mediate inflammation and fibrosis. Biomarkers such as 8-hydroxy-2′-deoxyguanosine, malondialdehyde, and NOX4 are consistently associated with disease progression. Emerging therapeutic strategies targeting oxidative pathways – such as Nrf2 activators and mitochondrial antioxidants – demonstrate promising potential. Therefore, OS plays a pivotal role in DN pathogenesis and progression. Targeted antioxidant therapies and early biomarker detection may improve disease management and clinical outcomes. Further clinical validation is required to translate these findings into practice.