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 < 0.08); 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.