NO in Diabetic Nephropathy

The incidence of diabetes mellitus has reached epidemic proportions; some 10-12 million people in the United States alone are afflicted with diabetes mellitus [1]. The vascular complications of diabetes represent major risk factors for cardiovascular morbidity and mortality. Diabetic nephropathy has emerged as the leading cause of end-stage kidney failure in many centers in the United States, and diabetic retinopathy is the leading cause of blindness. The risk of fatal myocardial infarction is increased threefold to fourfold in diabetic individuals. Diabetic nephropathy is essentially a microvascular disease of the kidneys [2]. The natural history of renal involvement in insulin-dependent diabetes mellitus is characterized by a spectrum of abnormalities, beginning with functional hemodynamic alterations [3], followed by structural alterations [4], which, in some 30-50% of subjects progress to end-stage renal failure. Renal blood flow and glomerular filtration rate are increased during the initiating phase of diabetes in both humans and in animal models. The recent discovery that nitric oxide (NO) serves as a physiologic modulator of renal blood flow and of glomerular filtration rate prompted investigators to examine the potential role of NO in the mediation of diabetes-induced hyperfiltration. NO-mediated responses appear to be enhanced during the initiating phase of experimental diabetes, but as the disease progresses, responses mediated by NO become impaired.