The Use of Mycophenolate Mofetil in Experimental Encapsulating Peritoneal Sclerosis

Abstract

Encapsulated peritoneal sclerosis (EPS) is a rare complication of long-term peritoneal dialysis usually associated with the inadequacy and early termination of dialysis modality. Adequate treatment of peritoneal fibrosis has not been achieved by medical intervention so far. Mycophenolate mofetil (MMF), which inhibits inosine monophosphate dehydrogenase reversibly and highly selectively, is the most widely used drug for maintenance immunosupression in renal transplantation. Recent studies have shown that MMF has also antifibrotic effects. In this study, we evaluated the effects of MMF on EPS model in rats based on antifibrotic effects.

Twenty-four Wistar albino rat have been randomly divided into four groups. Group I (control group) received isotonic saline intraperitoneally (i.p) 2 ml/day for (0-3rd weeks). Group II (chlorhexidine (CG) group) received CG 2 ml/day i.p. for (0-3rd weeks). Group III (chlorhexidine + MMF group) received CG (2 ml/day) i.p. for (0-3rd weeks) plus MMF 30 mg/kg/day peroral (4th-6th weeks). Group IV (resting group) received CG 2 ml/day) i.p. (0-3rd weeks) plus peritoneal resting without any treatment (4th-6th weeks) At the end of the sixth weeks, all of the rats were killed. All of the groups were analyzed in terms of peritoneal thickness, degree of inflammation, vasculopathy, neovascularization and fibrosis. Also, the parietal peritoneal tissue samples were evaluated for matrix metalloproteinase 2 (MMP-2) by using the immunohistochemical analysis.

When the CG group was compared with the MMF group, the medication resulted in a statistically significant reduction in peritoneal thickness, inflammation and fibrosis score (53.23 +/- A 16.24 vs. 17.22 +/- A 3.62, 1 +/- A 1.225 vs. 1 +/- A 0, 1.6 +/- A 0.548 vs. 0.2 +/- A 0.447, respectively, all p < 0.05). In the resting group, no beneficial effects on morphological abnormality of the peritoneum were observed as compared with MMF group. However, according to immunohistochemical analysis of the expression of MMP-2 on peritoneal samples, the highest expression of MMP-2 was observed in the MMF group.

MMF was effective for the treatment of encapsulating peritoneal fibrosis in our rat model. Most recently, MMF may be first choice for EPS due to antifibrotic effect.