Obesity and Diabetic Kidney Disease: Role of Oxidant Stress and Redox Balance.

SIGNIFICANCE: Reactive oxygen species (ROS) reactive nitrogen species (RNS) and redox processes are of key importance in obesity- and diabetes-related kidney disease; however, there remains significant controversy in the field. RECENT ADVANCES: New data from imaging and in vivo models of obesity and diabetic kidney disease have shed new insights into this field. In the setting of obesity- and diabetes-related kidney injury, there is a growing recognition that the major moieties of ROS and RNS are hydrogen peroxide and peroxynitrite with the enzymatic sources being NADPH oxidases and nitric oxide synthase, respectively. However, the role of mitochondrial superoxide as a driver of renal complications remains unclear. CRITICAL ISSUES: Several key issues that are often not discussed are the specific ROS and RNS molecules, the source of generation, the location of production, and downstream targets. FUTURE DIRECTIONS: Further understanding of the role of ROS/RNS/redox and their relationship with key signaling and metabolic pathways such as AMP-activated protein kinase (AMPK) and hypoxia-inducible factor 1-α (HIF1α) will be critical to a new understanding of kidney complications of caloric challenges and new therapeutic approaches. Antioxid. Redox Signal. 25, 208-216.