Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine (proteinuria or albuminuria), rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years. Pathophysiologic abnormalities in diabetic nephropathy usually begin with long-standing poorly controlled blood glucose levels. This is followed by multiple changes in the filtration units of the kidneys, the nephrons. (There are normally about 750,000–1.5 million nephrons in each adult kidney). Initially, there is constriction of the efferent arterioles and dilation of afferent arterioles, with resulting glomerular capillary hypertension and hyperfiltration particularly as nephrons become obsolescent and the adaption of hyperfiltration paradoxically causes further shear stress related damage to the delicate glomerular capillaries, further proteinuria, rising blood pressure and a vicious circle of additional nephron damage and decline in overall renal function. Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane, a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial matrix. This matrix invades the glomerular capillaries and produces deposits called Kimmelstiel-Wilson nodules.
Stephan Morgenthaler, Paul Refinetti, Mariya Yuryevna Skvortsova