ADVANCED GLYCATION ENDPRODUCTS AND DIABETIC NEPHROPATHY

Diabetic nephropathy is currently the single largest cause of endstage renal disease (ESRD) in the United States and many European countries . The primary cause for the development of diabetic complications (inc luding diabetic nephropathy) is persistent exposure to hyperglycemia, although genetic and other incompletely understood factors also play a n important role. Although much consideration has been given to the pa thogenesis and genetics of the disease itself, the mechanisms by which persistent exposure to hyperglycemia cause biochemical and metabolic alterations have been very sketchily understood. Recently, a growing b ody of evidence has linked the accumulation of the late products of gl ucose-protein interaction to a variety of chronic complications, inclu ding diabetic nephropathy. The formation of irreversible advanced glyc osylation endproducts (AGEs) resulting from the spontaneous reaction b etween glucose and proteins occur most noticeably on long-lived struct ural proteins. Recent studies demonstrate that the pathogenesis of dia betic nephropathy is caused by the hyperglycemia-accelerated formation of AGEs. Also, reactive AGE peptides in the circulation are thought t o play a role as a new version of so called middle molecule toxic subs tances. This evidence is opening a new window for our understanding of the pathogenesis of diabetic nephropathy.