Pathophysiology of Diabetic Nephropathy

Diabetic nephropathy affects approximately 25–35% of patients with diabetes mellitus, whether type 1 or type 2. The disease progresses through various clinical stages from hyperfiltration, to microalbuminuria, to macroalbuminuria, to nephrotic proteinuria, to progressive chronic kidney disease that eventually leads to end-stage renal disease. These stages are generally associated with structural pathological changes affecting all compartments of the kidney: the glomerulus, the tubules, the vasculature, and the interstitium. With the increased glycemia, various metabolites and by-prodcuts, including advanced glycation end products and reactive oxygen species, are stimulated. These metabolic insults converge with the main driver of the hemodynamic insult, angiotensin II, to induce diabetic renal pathology at its different levels. The advances in genetics and molecular biology will continue to reveal more about the pathogenesis of diabetic nephropathy, but the multifactorial nature of the disease has defied attempts at a general theory that unifies all the known cellular and biochemical pathways.