Hyperglycemia-induced microvascular disease is the fundamental cause of diabetic kidney disease. More specifically, hyperglycemia perturbs metabolic pathways, particularly in tissues that do not regulate intracellular glucose levels. This favors a broad range of pathogenic oxidative chemistries including the formation of advanced glycation end-products (AGEs), toxic carbonyls, and reactive oxygen species (ROS) that are considered to be the principal causative factors in the development of diabetic microvascular disease.