Advanced glycosylation end products in diabetic renal and vascular disease.

An increasing body of experimental data supports the important, etiologic role of advanced glycosylation end products (AGEs) in the development of the renal and vascular complications of diabetes. Advanced glycosylation end products arise from glucose-derived Amadori products and act to increase vascular permeability, enhance protein and lipoprotein deposition, inactivate nitric oxide, and promote matrix protein synthesis and glomerular sclerosis. Loss of normal renal function increases the level of circulating plasma AGEs and contributes markedly to their ultimate tissue toxicity. Aminoguanidine, a recently developed pharmacologic inhibitor of advanced glycosylation, is presently undergoing phase II/III clinical trials in diabetic nephropathy and may offer a specific therapeutic modality for diminishing the formation and toxicity of AGEs.