Anatomic Pathology: Renal Pathology

• Diabetic nephropathy develops in approximately 50% of patients with diabetes mellitus. Diabetic nephropathy is the major cause of end-stage renal disease in the United States and much of the developed world.

• The basic lesion of diabetes mellitus is a progressive thickening of capillary and arteriolar basement membranes throughout the body (microangiopathy). This process is due to excessive synthesis of collagenous proteins and glycoproteins resulting from abnormal glucose metabolism, which promotes glycosylation of basement membrane proteins and the formation of advanced glycation end-products. Major target organs are kidneys, retinas, heart, major blood vessels, and nerves. Generally, diabetic retinopathy and diabetic nephropathy develop concurrently (i.e., it is highly unusual for a patient to have diabetic nephropathy without evidence of diabetic retinopathy).

• Diabetic nephropathy is characterized by thickening of basement membranes throughout the kidney, including mesangial matrix, glomerular basement membrane (GBM), tubular basement membrane, interstitial capillary basement membrane, and the walls of arteries and arterioles.

• Mesangial sclerosis often forms nodules (Kimmelstiel-Wilson nodules). There may be dilatation of glomerular capillaries surrounding the nodules, producing glomerular capillary microaneurysms that are analogous to the microaneurysms in the retina.

• Clinically, the first sign of diabetic nephropathy is mild proteinuria (microalbuminuria), which may precede by years the development of full nephrotic syndrome or renal insufficiency.