Carbonyl Stress: Increased Carbonyl Modification of Proteins by Autoxidation Products of Carbohydrates and Lipids in Uremia

Advanced glycation end-products (AGEs) are formed during non enzymatic glycation and oxidation (glycoxidation) reactions. This process is accelerated in diabetics owing to hyperglycemia, and it has been implicated in the pathogenesis of diabetic complications. Surprisingly, AGEs increase in normoglycemic uremic patients to a much greater extent than in diabetics. AGE accumulation in uremia cannot be attributed to hyperglycemia nor simply to a decreased removal by glomerular filtration. Recently gathered evidence has suggested that, in uremia, the increased carbonyl compounds derived from carbohydrates and lipids modify proteins not only by glycoxidation reaction but also by lipoxidation reaction ("carbonyl stress"). Carbonyl stress has been implicated in the pathogenesis of long-term uremic complications such as dialysisrelated amyloidosis. With regard to continuous ambulatory peritoneal