Diabetic nephropathy is a progressive renal disease and represents a serious late complication of diabetes. There are familial clustering and huge ethnic differences in the occurrence of diabetic nephropathy, which point to a genetic predisposition. Diabetic nephropathy is defined by persistent albuminuria (albumin excretion rate [AER] > 300 mg/day), declining glomerular filtration rate and rising blood pressure. Several years of incipient nephropathy, characterized by worsening microalbuminuria (AER 30 to 300 mg/day or 20 to 200 micrograms/min), which is Albustix-negative and detectable by special assays only, are followed by established nephropathy. The natural history of nephropathy differs between insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In IDDM, nephropathy develops in 30 to 40% of cases. The incidence peaks after 15 to 16 years of diabetes. In NIDDM, estimates of prevalence range from 15 to 20%, and nephropathy often supervenes after a shorter known duration of diabetes than in IDDM. GFR is often increased above normal (hyperfiltration) from the onset of IDDM due to increased renal blood flow, glomerular capillary hypertension and increased filtration surface. The glomeruli are hypertrophied and the kidneys enlarged. In both IDDM and NIDDM, GFR begins to decline irreversibly, when AER has risen to 100 to 300 mg/day at an average rate of 10 ml/min. per year. This is due to progressive reduction of the filtration surface area through mesangial expansion. Serum creatinine levels begin to rise when GFR falls below 50 ml/min, and then end-stage renal failure follows after an average of five years.(ABSTRACT TRUNCATED AT 250 WORDS)