Sulodexide modulates the dialysate effect on the peritoneal mesothelium.

Abstract

Peritoneal membrane damage during chronic peritoneal dialysis is the main cause of that treatment failure. Preservation of the mesothelial cells (MC) is important for the survival of the peritoneum. Evaluation of dialysates effect on the function of MC and potential modification of that effect by sulodexide (heparin 80% and dermatan sulfate 20%). Dialysate effluents, after the overnight exchange with dianeal 1.5% dextrose, were collected from 7 continuous ambulatory peritoneal dialysis (CAPD) patients, and their effect ± sulodexide 0.5 LRU/mL on genes expression, secretory activity and protein synthesis in MC was studied. Exposure of MC to the studied dialysates caused intracellular oxidative stress and significantly increased expression of the genes regulating the synthesis of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-beta (TGF-β), vascular cell adhesion molecule 1 (VCAM-1) and vascular endothelial growth factor (VEGF). Secretion of the studied molecules from MC treated with dialysates was increased: by 96% for IL-6 (P < 0.01), 34% for MCP-1(P < 0.01), 24% for TGF-β (P < 0.01), 27% for VCAM-1 (P < 0.01), and by 15% for VEGF (P < 0.01). Sulodexide reduced the stimulatory effect of the dialysates on the intracellular generation of free radicals, genes expression and secretory activity of MC. These cells exposed to the dialysates showed increased synthesis of total protein (by 216%, P < 0.005) and collagen (by 264%, P < 0.005), as compared to standard culture medium. Supplementation of the dialysates with sulodexide resulted in weaker stimulation of collagen synthesis (-21% versus dialysate). We concluded that peritoneal dialysate changes the genes expression and phenotype of MC to a proinflammatory, profibrotic and proangiogenic one. Sulodexide reduces these negative effects of the dialysate.