Andrzej Breborowicz

In vitro simulation of the effect of peritoneal dialysis solution on mesothelial cells

All previous in vitro biocompatibility tests of peritoneal dialysis fluids have shown that these have inhibitory effects on the function of peritoneal mesothelium. This report presents results from in vitro experiments performed to study the effect of dialysis fluids (Dianeal 1.36 and Dianeal 3.86; Baxter, Round Lake, IL) on the function of mesothelial cells under conditions that simulate the in vivo state of these solutions in the peritoneal cavity. Thus, cells were initially exposed only to the unused fluids that were thereafter gradually diluted (over 4 hours) with pooled effluent dialysate from continuous ambulatory peritoneal dialysis patients. During the following 20 hours, cells were incubated in a mixture of unused fluid (10% vol/vol) and dialysate effluent (90% vol/vol). The mesothelial cells exposed to dialysis fluids under such conditions became activated cells compared with exposed to dialysate effluent (control) alone. Thus, synthesis by mesothelial cells of all tested substances was enhanced during exposure of the mesothelium to the dialysis fluids: interleukin-6: Dianeal 1.36, +257%; Dianeal 3.86, +181% (both P < 0.05); hyaluronic acid: Dianeal 1.36, +72%; Dianeal 3.86, +63% (both P < 0.05); tissue plasminogen activator: Dianeal 3.86, +33% (P < 0.05); and plasminogen activator/inhibitor-1: Dianeal 1.36, +28%; Dianeal 3.86, +38% (both P < 0.05). Our results show that the peritoneal mesothelium becomes activated when it is exposed to acidic, hyperosmotic dialysis fluids diluted with the dialysate effluent, in a manner that imitates the in vivo changes in these solutions during their intraperitoneal dwell.

EFFECTS OF HYALURONAN USED AS A SUPPLEMENT IN PERITONEAL DIALYSIS SOLUTIONS

ABSTRACT Hyaluronan present in the peritoneal cavity is removed during the course of peritoneal dialysis. The addition of hyaluronan to dialysis fluids has been proposed as a means to improve peritoneal transport functions and to protect the peritoneal membrane during peritoneal dialysis. Studies in rats have examined the effect of hyaluronan, added to dialysis solutions, on peritoneal permeability, inflammation and morphology. Addition of 10 mg/dL high-molecular weight (hmw) hyaluronan (m.w. 1.8-2.4 × 10 6 D) to the dialysis solution caused significant improvements in fluid and solute transport. Net ultrafiltration of water across the peritoneum increased, whereas the membranes permeability to protein declined. During an eight hour dwell in the peritoneal cavity, about 25% of the administered hyaluronan was absorbed, and concentrations in the peritoneal interstitium and in blood increased significantly. Absorbed hyaluronan was rapidly metabolised and, was not affected by the uremic status of the animal. Hyaluronan reduced the acute intraperitoneal inflammation induced by the initiation of peritoneal dialysis and the surgical procedure. In rats exposed to dialysis solution supplemented with hyaluronan (10 mg/dL) for one month, the interstitial connective tissue in the peritoneal membrane was less thickened than that of control rats, and the membrane had a lower permeability to protein and reduced hydraulic conductivity. potentially helping to promote the removal of water during dialysis. Thus, supplementation of peritoneal dialysis solutions with hyaluronan may improve peritoneal transport and fluid removal while helping to reduce peritoneal inflammation caused by the dialysis procedure.