#591 A murine model of peritoneal fibrosis in adenine-induced chronic kidney disease

Abstract Background and Aims Peritoneal fibrosis is a complication in end-stage-renal-disease patients undergoing peritoneal dialysis, leading to peritoneum function failure. However, most studies investigate peritoneal fibrosis using animals with normal renal function. This study establishes a murine model of peritoneal fibrosis in adenine-induced chronic kidney disease. Method 6-week-old C57BL/6 mice were fed a 0.2% adenine diet for 6 weeks to induce chronic kidney disease. A single intraperitoneal injection of 0.05% Sodium hypochlorite (NaClO) was used to induce peritoneal fibrosis. After 7 days of NaClO injection, mice were sacrificed and plasma was collected to measure renal function. The adhesion score evaluated the intent of peritoneal fibrosis and Masson's trichrome stain quantified the thickness of the peritoneal membrane. The peritoneal equilibration test was performed by injecting 2 mL 2.5% peritoneal dialysis solution for 30 minutes, to assess the changes in the peritoneal solute transport rates and ultrafiltration volume. Results In the adenine-CKD group, each mouse consumed an average of 3.14 g of food daily, equivalent to 6.28 mg of adenine per day. Blood urea nitrogen and creatinine levels were significantly elevated in the adenine-CKD group. (Fig. 1) After NaClO injury, peritoneal adhesion scores were significantly higher in both the normal and adenine groups, especially the adenine group. Peritoneal adhesions in the adenine group were particularly observed in the intestines and omentum. (Fig. 2A) Thickening of the parietal and visceral peritoneal membrane was observed in NaClO-injured mice, with no differences in the two diets. (Fig. 2B) The peritoneal equilibration test showed that NaClO-injured mice absorbed more glucose from the dialysate, resulting in a corresponding decrease in net ultrafiltration. (Fig. 2C and D) Conclusion NaCIO-induced peritoneal fibrosis led to thickened, adhesive peritoneal membranes and a loss of the osmotic gradient, resulting in reduced water removal. Although the adenine group exhibited higher adhesion scores, the decline in renal function did not affect membrane thickening, peritoneal solute transport, or ultrafiltration. This model is relevant to human patients with peritoneal fibrosis and impaired renal function.