Carbonyl stress: Increased carbonyl modification of tissue and cellular proteins in uremia

Advanced glycation end-products (AGEs) are formed during non enzymatic glyc ation and oxidation (glycoxidation) reactions. This process is accelerated in diabetics owing to hyperglycemia, and it has been implicated in the path ogenesis of diabetic complications. Surprisingly, AGEs increase in normogly cemic uremic patients to a much greater extent than in diabetics. AGE accum ulation in uremia cannot be attributed to hyperglycemia nor simply to a dec reased removal by glomerular filtration. Recently gathered evidence has sug gested that, in uremia, the increased carbonyl compounds derived from carbo hydrates 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 dialysis-related amyloidosis. With regard to continu ous ambulatory peritoneal dialysis (CAPD), the peritoneal cavity appears to be in a state of severe overload of carbonyl compounds derived from CAPD s olution containing high glucose, from heat sterilization of the solution, a nd from uremic circulation. Carbonyl stress might modify not only peritonea l matrix proteins and alter their structures, but also react with mesotheli al and endothelial cell surface proteins and initiate a range of inflammato ry responses. Carbonyl stress might therefore contribute to the development of peritoneal sclerosis in patients with long-term CAPD.