End-stage renal failure is a severe and relatively frequent complication of insulin-dependent diabetes, also representing the only growing cause of uremia requiring replacement therapy in Western countries. Five principal pathogenic factors are to be considered: genetic, immunologic, hemorheologic, biochemic, and hemodynamic; of these, nonenzymatic glycosylation of proteins and glomerular hyperfiltration appear to be most important. In the last few years, a better understanding of the natural history of type I diabetes has been gained, with particular significance attributed to the stage of the disease defined as incipient diabetic nephropathy which is characterized by microalbuminuria. However, advances in pathophysiologic notions have not always been followed by corresponding results in the prevention and therapy of diabetic nephropathy; possible reasons for this are briefly discussed. In spite of these uncertainties, the importance of achieving the best possible correction of glycemic homeostasis and of albeit initial elevations in the arterial pressure appears to be well established.

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