Abstract
Loss of ultrafiltration is one of the important complications to deny the longterm continuation of CAPD therapy. The low pH and high osmotic pressure of the dialysate are often pointed out as the causes of the ultrafiltration loss. We prepared sodium chondroitin sulfate (CHS) as a dialysate osmotic agent that was considered to have a protective effect on the peritoneum. And we investigated its usefulness in an animal model (CAPD rabbits; in vivo), and in cultured human peritoneal mesothelial cells (in vitro). We prepared glucose containing dialysates (PERITOLIQ®: P135, P250, P400) as a control, CHS-containing dialysates of the same osmolality as these three, and a CHS 1.5%-containing dialysate of 290mOsm/L. One hundred fifty-ml quantities of one these dialysates was infused into the peritoneal cavity of a each of three CAPD rabbits, and the effluent was measured for 24 hours after the infusion. Such dialysates were infused once daily for 4 weeks and the peritoneal function was studied by performing PET once weekly. Also, to investigate the cytotoxicity of the CHS-containing dialysate, we incubated human peritoneal mesothelial cells for 6 hours in each dialysate and measured their 51Cr release into the medium. As a result, the effluent volume was decreased over time in the three PERITOLIQ-dialysate groups, and at 24 hours after the infusion no effluent was obtained at all. CHS-containing dialysates, however, produced an effluent which was increased in a dose-dependent manner, and its volume was maintained satisfactorily even after 24 hours. Regarding the effluent volume measured at the weekly PET, it was impossible to measure it in the CHS250 and CHS400 groups, and there were about a 70 percent decrease in the P250 and P400 groups, about a 40 percent decrease in the P135 and CHS135 groups, but only a slight decrease (about 15 percent) in the CHS 1.5% group. The higher the osmolality of the dialysates containing PERITOLIQ or CHS, the more cytotoxic they were for cultured human mesothelial cells. Based on the observations that the effluent could be retained when the CHS-containing dialysate was used even at low osmolality and that its pH could be easily neutralized, CHS was considered to be an effective osmotic agent.