The effect of steroid-sirolimus combination on the experimental model of sclerosing encapsulated peritonitis in rats

Peritoneal dialysis (PD) , an alternative renal replacement treatment modality for end stage renal failure patients, has some serious complications that limits it for long-term use besides its certain advantages. Major complications are bacterial peritonitis and sclerosing encapsulated peritonitis (SEP). SEP is a clinical syndrome resulting from the pathologic processes that terminate with peritoneal sclerosis and coccooning of intestinal loops. It is a nadir but seriously fatal complication of PD. Major risk factors playing role in development of SEP are prolonged PD duration, infectious peritonitis episodes, exposure of peritoneal membrane to bioincompatible solutions, EMT, and cessation of PD. SEP occurring in PD patients who underwent renal transplantation has been attributed to the use of profibrotic effects of calcineurine inhibitors of immunosuppressive regimens. At present there is not any established treatment modality for SEP. The effects of some immunosuppressive agents have been documented in both human and experimental studies. The inhibitors of mammalian target of rapamycin (mTOR), everolimus and sirolimus, have attenuated SEP findings in experimental rat models. The effect of combination of sirolimus with steroid has not been documented so far. Objective : The aim of the study was to determine the effect of combination of sirolimus and steroid on experimental SEP model developed in rats. Materials and method : 42 wistar albino male rats were divided into 6 groups : 1) control group (C), 2 ml isotonic saline injected intraperitoneally (i.p) daily for 3 weeks, 2) chlorhexidine gluconate group (KG), 2 ml 0.1%CG and 15% ethanol dissolved in saline injected i.p daily for 3 weeks ,3) resting group (R) , CG for three weeks plus 3 weeks peritoneal rest, 4) prednisolone group (P), CG for 3 weeks and then prednisolone 0.1mg/kg (10 mg in 1 L tap water) for 3 weeks by feeding tube, 5) sirolimus group (Sir), CG for 3 weeks and then oral sirolimus ( 1mg /kg/day) for 3 weeks , 6) prednisolone-sirolimus group (P-Sir), CG for 3 weeks and then orally prednisolone and sirolimus for 3 weeks. At the end of 6 weeks rats were sacrified by ether anestezia. The specimens were collected from opposite siye of injection for parieatal peritoneum and from liver surface for visceral. The specimens were stained by Hematoxylen & Eosin (HE) and Mason Trichrome (MT) dyes for pathologic examinations. Peritoneal thickness, fibrosis, and vascular intensity were determined under light microscopy. Results : In the CG and R groups there was a significant increase in peritoneal thickness, fibrosis score and vascular intensity compared to C, P, Sir, and P-Sir groups in both parietal and visceral peritoneum (p<0.05). The parameters at the end of the study were not different in C, P, Sir , and P-Sir groups. The difference between P, Sir, and P-Sir groups were not significant. Resting was shown to be ineffective in attenuating SEP parameters. Conclusion : In this study we observed that sirolimus-prednisolone combination was equally effective in experimental SEP model compared to prednisolone and sirolimus only regimens. Key words : Sclerosing encapsulated peritonitis, sirolimus, immunosuppressive therapy