genitourinary disorders
Diabetic Nephropathy
Pathophysiology of Diabetic Nephropathy
Pathogenesis begins with small vessel disease. Pathophysiology is complex, involving glycosylation of proteins, hormonally influenced cytokine release (eg, transforming growth factor-beta), deposition of mesangial matrix, and alteration of glomerular hemodynamics. Hyperfiltration, an early functional abnormality, is only a relative predictor for the development of renal failure. Hyperglycemia causes glycosylation of glomerular proteins, which may be responsible for mesangial cell proliferation and matrix expansion and vascular endothelial damage. The glomerular basement membrane classically becomes thickened. Lesions of diffuse or nodular intercapillary glomerulosclerosis are distinctive; areas of nodular glomerulosclerosis may be referred to as Kimmelstiel-Wilson lesions. There is marked hyalinosis of afferent and efferent arterioles as well as arteriosclerosis; interstitial fibrosis and tubular atrophy may be present. Only mesangial matrix expansion appears to correlate with progression to Chronic Kidney Disease . Mesangial cell proliferation and matrix expansion with endothelial damage are manifest here as thickened glomerular basement membranes without evident immune complex deposits (periodic acid-Schiff stain,×400). Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). Formation of acellular nodules within mesangial matrix is a distinctive feature of diabetic nephropathy (periodic acid-Schiff stain,×200). Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). Hyalinosis of both afferent and efferent arterioles. Image provided by Agnes Fogo, MD, and the American Journal of Kidney Diseases'Atlas of Renal Pathology(see www.ajkd.org). Diabetic nephropathy begins as glomerular hyperfiltration (increased glomerular filtration rate [GFR]); GFR normalizes with early Acute Kidney Injury (AKI) and mild Other urinary tract abnormalities commonly occurring with diabetic nephropathy that may accelerate the decline of renal function include papillary necrosis, type IV Renal Tubular Acidosis , and 