Advanced glycosylated end-products (AGEs) in non-diabetic patients undergoing dialysis.

Renal failure is associated with the accumulation of advanced glycosylated endproducts as a consequence of an impaired renal clearance. We confirmed the finding that in sera of ESRD patients the AGE-β 2 -microglobulin fraction is significantly elevated in contrast to healthy controls but also to diabetic patients without dialysis. Furthermore, we investigated the question, as to whether the continuously high glucose concentration in the abdominal cavity of CAPD patients leads to a local production of AGE. We found increased levels of AGE in the dialysate of CAPD patients after long dwell times as compared to the serum concentrations. In immunohistochemical studies we proved the presence of high amounts of AGE in the mesothelial and submesothelial tissue of patients on perennial CAPD. In in vitro experiments mesothelial cells, cultured on glyosylated collagen, showed a disturbed, net-like growth and an impaired matrix production. Further studies demonstrated that the disturbed matrix production was paralleled by an impaired production of the metalloproteinase gelatinase and its natural inhibitors TIMP-1 and TIMP-2. These alterations may (at least in part) be responsible for the long-term damage of the peritoneal membrane observed in CAPD patients.