Recent advances in understanding mechanisms and natural history of diabetic renal disease.

A large subset of individuals with insulin-dependent diabetes mellitus (IDDM) develops clinical nephropathy that progresses to end-stage renal failure. Identification of clinically proteinuric patients has limited impact on management of the condition. No treatment strategy has succeeded in permanently arresting the evolution of clinical nephropathy. However, important advances have been made in slowing its progress, and these are reviewed in this study. Treatment of raised blood pressure early in the course of diabetic renal disease has emerged as the most effective therapeutic measure. Susceptible individuals can be detected before persistent proteinuria becomes manifest by screening IDDM patients for microalbuminuria, which has proved predictive of persistent proteinuria in approximately 80% of cases. Microalbuminuria can be associated with a raised glomerular filtration rate and is often accompanied by subclinical increases in arterial blood pressure. The independent predictive significance of the two latter variables remains to be established in humans. Unfortunately, microalbuminuria is not apparent until 5 yr after stabilization of newly diagnosed diabetes, suggesting that it is a marker of early disease rather than an indicator of susceptibility. However, many therapeutic interventions, ranging from blood glucose control to low-protein diet and angiotensin-converting enzyme inhibition, are effective in reducing or even normalizing microalbuminuria. If current controlled trials show that treatment of microalbuminuric patients prevents progression to clinical nephropathy, the diagnostic criteria for diabetic renal disease will require radical revision.