Three stimuli prompt reexamination of the course of end-stage renal disease (ESRD) in diabetes mellitus: (1) The remarkable pandemic of type 2 diabetes that is still in its growth phase1,2; (2) the belief that careful study of metabolic events during the course of diabetes will yield insight into the pathogenesis of cardiovascular complications that end life in both diabetic and nondiabetic patients with ESRD3,4; and (3) emerging interventions based on molecular biology that promise interdiction of diabetic complications, including kidney failure.s In 1985, Mauer and Chavers wrote that "diabetes is the most important cause of ESRD in the Western world,"6 superceding glomerulonephritis and hypertensive renal disease in incidence and prevalence. At least 16 million people in the United States have diabetes, but more than one third are unaware of the disorder. As recounted by the Centers for Disease Control in the National Diabetes Fact Sheet,? in 1999, in the United States, 798,000 people developed newly diagnosed diabetes, and 187,000 of these died of diabetes. With some variation in age, race, and sex, diabetes in 1996 ranked from the 8th (white men aged 45 to 65 years) to the 4th (black women aged 45 years and over) leading cause of death.8 The financial burden for health care expenditures generated by diabetes in the United States ranges 1999