Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration

Background. Ultra-filtration failure is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD). This complication is related to histological changes of the peritoneum, i.e. severe interstitial fibrosis and microvascular sclerosis. Although their pathogenesis has not been elucidated yet, advanced glycation end products (AGEs) have been shown to accumulate in the peritoneal tissue of CAPD patients. Methods. Peritoneal biopsy specimens from 14 CAPD patients with low ultra-filtration (n =9) and high ultrafiltration (n=5) capacity were immunohistochemically investigated using a monoclonal antibody against AGEs (6D12). The severity of peritoneal fibrosis, microvascular sclerosis and intensity of AGE accumulation were semi-quantitatively evaluated. Peritoneal ultra-filtration capacity was evaluated by calculating daily ultrafiltration volume per body weight (UFV/BW) and D/D-0 (glucose) of the peritoneal equilibration test. Results. In all patients with low ultra-filtration, AGE accumulated in the peritoneal fibrous tissue and microvascular walls. Remarkably, AGE accumulated more intensely in hyalinized fibrosis of small venular media. Extent of AGE accumulation in peritoneal interstitium and vascular walls correlated with the progression of interstitial fibrosis (p=0.727, P=0.0088) and vascular sclerosis (rho = 0.915, P = 0.001). UFV/BW was inversely correlated to interstitial fibrosis (rho=-0.660, P=0.0174), microvascular sclerosis (rho=-0.671, P=0.0155) and microvascular AGE accumulation (rho=-0.678, P=0.0145). Conclusions, In CAPD patients, AGE formation in the peritoneum correlates with the development of severe interstitial fibrosis and microvascular sclerosis, which is associated clinically with impaired peritoneal ultra-filtration.