Effect of Drug Additives to Peritoneal Dialysis Solutions on the Viability and Function of Mouse Peritoneal Cells

Abstract

Peritoneal dialysis (PD) solutions and therapeutic drugs frequently added to PD solutions in clinical practice have been shown to reduce the viability and to impair the function of mouse peritoneal cells. The cytotoxicity of PD solutions, directly related to the dextrose concentration, was more marked towards resident than elicited peritoneal cells. None of the drug additives, heparin and insulin amongst them, were cytotoxic when tested alone or combined with 4.25% PD solution, with the exception of phosphatidylcholine which markedly enhanced the cytotoxicity of the PD solution. While the function of mouse peritoneal macrophages as measured by their hydrogen peroxide production was largely unaffected by PD solutions and drug additives when tested separately, the combination of 4.25% PD solution with any of the drug additives resulted in complete abolition of macrophage respiratory burst. The results should caution against the indiscriminate addition of drugs to PD solutions in dialysis patients.

Biocompatibility of a Glucose-Free, Acidic Lactated Solution for Peritoneal Dialysis Evaluated by Population Analysis of Mesothelium

“…Conversely, the reduced viability of mesothelium treated with acidic fluids was mainly attributed by other investigators to the low pH of the solution [14]. It is interesting to note that other in vitro studies, exposing peritoneal macrophages [2] or mesothelial cells [3] to high-glucose, lactated, and acidic solutions for PD, suggested a relevant cytotoxic effect of the glucose concentration per se.…”

“…Several lines of investigation revealed detrimental effects induced by glucose-enriched, lactate-buffered peritoneal dialysis (PD) solutions, commonly used in clinical wards upon acutely exposed mesothelial cells in culture [1, 2, 3, 4]. The detected changes included: reduced cell viability [2, 3, 4], a substantial decrease of interleukin 6 and prostaglandin F 1α synthesis [5], inhibition of cell proliferation [6], a drop in the intracellular concentration of reduced glutathione [7], and even increased generation of hydrogen peroxide [8].…”

“…The detected changes included: reduced cell viability [2, 3, 4], a substantial decrease of interleukin 6 and prostaglandin F 1α synthesis [5], inhibition of cell proliferation [6], a drop in the intracellular concentration of reduced glutathione [7], and even increased generation of hydrogen peroxide [8]. Although this information is not to be overlooked, its relevance vis-à-vis the in vivo biocompatibility is still unclear.…”

Effect of Phosphatidylcholine on the Function of Human Mesothelial Cells in vitro

“…We pro pose that even a low-concentration chronic intraperitoneal administration of phosphatidylcholine may disturb the functional integrity of the mésothélium. Furthermore, Gag-non et al [4] showed that phosphatidylcholine cytotoxicity on peritoneal macrophages increases when the cells are incubated in hypertonic fluid rather than in the buffered medium. Based on this observation, one may speculate that in vivo repair of injured cells is more efficient than in vitro when the cells are cultured in medium, the composition of which only partially resembles the composition of body fluid: we propose that our observations on the toxicity of various factors (osmotic solutes, antiseptics, phosphatidylchonile) to mesothelial cells in vitro reflect the real situation in vivo although the intensity of this process in the body milieu may be lower.…”

Free Radicals in Peritoneal Dialysis: Agents of Damage?

“…Peritoneal macrophages and neutrophils are potential sources of free radicals. However, the high osmolality and low pH of the dialysis solution is toxic to these cells, reducing their viability (51,52,53) and decreasing their capacity to generate oxygen-derived free radicals (54)(55)(56). During peritoneal dialysis, the pH of the dialysate solution is adjusted to normal within 30 60 min (57), while its osmolality is continuously decreasing due to absorption of osmotic solutes and flow of water into the peritoneal cavity.…”