Diabetic nephropathy (DN) is the primary cause of chronic kidney disease in individuals with diabetes. Increasing evidence implicates hyperglycemia-induced mitochondrial dysfunction and overproduction of mitochondrial reactive oxygen species (mtROS) as significant contributors to diabetic kidney disease (DKD). This review aimed to elucidate the role of mitochondrial oxidative stress in the progression of DKD and to assess emerging therapeutic strategies targeting mitochondria. A comprehensive analysis of both experimental and clinical studies was conducted, focusing on the mitochondrial mechanisms underlying DKD and therapeutic approaches, including conventional renoprotective agents and mitochondria-targeted interventions. Hyperglycemia enhances electron transport chain activity, leading to excessive mtROS generation and activation of inflammatory, fibrotic, and apoptotic signaling pathways. Current therapies, such as SGLT2 inhibitors, RAAS blockade, and systemic antioxidants, provide partial protection, but do not directly address mitochondrial oxidative stress. Emerging strategies, including mitochondria- targeted antioxidants, Nrf2 activators, mitophagy inducers, and nanoparticle-based delivery systems, have shown promising renoprotective effects in preclinical and early clinical studies. Targeting mitochondrial dysfunction represents a promising therapeutic paradigm for DKD. Future research should prioritize the development of precise mitochondrial delivery systems, sensitive mitochondrial biomarkers, and rational combination therapies to enhance clinical translation and patient outcomes.
Goutam et al. (Thu,) studied this question.