A two-hit approach in the development of an experimental peritoneal sclerosis model

Models of encapsulating peritoneal sclerosis (EPS) are often based on local administration of chemical irritants. Our aim was to develop a clinically relevant "two-hit" model with incorporation of renal failure and exposure to conventional dialysis solutions. We randomly allocated 36 male Wistar rats that had undergone catheter implantation and a 70% nephrectomy to 3 peritoneal infusion groups. The experimental group was exposed to a 3.86% glucose-based conventional dialysis solution for 8 weeks, after which the animals received a second hit of intraperitoneal blood administration. Two weeks later the rats were humanely euthanized The two control groups were exposed to the conventional dialysis solution alone or to a buffer without glucose for 8 weeks. All animals underwent a peritoneal function test at the end of the experiment. Peritoneal adhesions were counted at autopsy, and omental tissue was obtained for morphometrics. The rats that received blood as a second hit developed numerous intraperitoneal adhesions as seen in EPS, but without cocoon formation. Microscopically, no differences in fibrosis scores and vessel counts were observed between the groups. Peritoneal function parameters were also similar in all groups. The short infusion period could be the reason that we found no differences between the groups, with the exception of the large amount of intraperitoneal adhesions in the experimental group. Modifications to the described rat model are required to develop a clinically relevant EPS model. Besides renal failure and long-term exposure to bioincompatibleperitoneal dialysis solutions, a different second hit or several additional hits could be incorporated into an experimental model of EPS.