Role of advanced glycation end products and growth factors in peritoneal dysfunction in CAPD patients

Abstract

High levels of glucose degradation products in peritoneal dialysis fluids are believed to cause excess accumulation of advanced glycation end products (AGEs) in the peritoneum during continuous ambulatory peritoneal dialysis (CAPD) treatment, resulting in functional and structural changes in the peritoneal membrane of CAPD patients. In this study, we investigated whether AGEs, the receptor for AGE (RAGE), and growth factors are involved in deteriorating ultrafiltration (UF) capacity of the peritoneal membrane in patients on CAPD therapy. Immunohistochemical staining showed that ODI-GLC19, a novel monoclonal anti-AGE antibody, was localized exclusively in peritoneal cells, in contrast to imidazolone, localized mostly in peritoneal degenerative collagen. Numbers of ODI-GLC19- and RAGE-positive cells in the peritoneum were increased significantly in CAPD patients, even before a decrease in UF capacity, compared with patients with nonrenal disease. Cells positive for ODI-GLC19 were identified as myofibroblasts and RAGE-positive cells and partly as CD68-positive macrophages in the peritoneum. The peritoneal membrane was thickened significantly in CAPD patients, especially patients with low UF. The number of blood vessels was increased significantly in CAPD patients with low UF. Transforming growth factor-beta1, macrophage colony-stimulating factor, and vascular endothelial growth factor were recognized in the peritoneum of CAPD patients, especially those with low UF, where imidazolone was deposited. Focal hepatocyte growth factor expression was noted in the peritoneum of patients with low UF in moderate intensity, specifically in the area without severe structural changes. In conclusion, progressive accumulation of AGEs in the peritoneum may promote peritoneal expression of various growth factors and subsequently deteriorate UF capacity in CAPD patients.