Mitochondrial Oxidative Stress and Vascular Remodeling in Uric Acid Nephropathy: Mechanistic Insights and Therapeutic Implications.

Abstract

Uric acid nephropathy (UAN), driven by sustained hyperuricemia, is an underrecognized but increasingly prevalent contributor to chronic kidney disease (CKD) progression. Mitochondrial oxidative stress and vascular remodeling are central to its pathogenesis. Excess mitochondrial reactive oxygen species (ROS) cause renal tubular injury, impair mitophagy, and activate pro-apoptotic signaling pathways. In parallel, ROS disrupt endothelial homeostasis, promote phenotypic switching of vascular smooth muscle cells, and induce pathological structural changes in the renal microvasculature. These processes are mutually reinforcing, thereby exacerbating inflammation, hypoxia, and fibrosis. This review synthesizes emerging mechanistic insights into the mitochondrial-vascular axis in UAN and discusses therapeutic strategies targeting mitochondrial dysfunction and vascular pathology. Particular emphasis is placed on mitochondria-targeted antioxidants and inhibitors of key signaling pathways as potential interventions to interrupt the ROS-remodeling cycle. We also highlight the need for biomarker development and clinical translation. A more comprehensive understanding of mitochondrial-vascular crosstalk may ultimately enable the development of effective strategies to slow or halt UAN progression.