Rosiglitazone, a peroxisome proliferator-activated receptor agonist, improves peritoneal alterations resulting from an encapsulated peritoneal sclerosis model.

Inflammation, fibrosis, and angiogenesis underlie the pathophysiology of encapsulating peritoneal sclerosis (EPS). The irreversible sclerosis of visceral and parietal peritoneum that characterizes EPS can be seen in peritoneal dialysis (PD) patients after long periods on dialysis. Peroxisome proliferator-activated receptors (PPARs) are the major regulator of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The aim of the present study was to investigate the effect of the PPAR agonist rosiglitazone on the progression and regression of peritoneal alterations in chlorhexidine gluconate-induced EPS in rats. We divided 53 nonuremic Wistar albino rats into 5 groups: control group--isotonic saline 2 mL, injected intraperitoneally (IP) daily for 3 weeks; chlorhexidine gluconate (CG) group--CG 2 mL per 200 g body weight, injected IP daily for 3 weeks; Rozi-P group--CG injection as described, plus rosiglitazone in drinking water (8 mg/L) for 3 weeks; resting group--CG injection as described during weeks 1 - 3, then peritoneal rest during weeks 4 - 6; Rozi-R group--CG injection as described during weeks 1 - 3, then rosiglitazone in drinking water (8 mg/L) during weeks 4 - 6. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed with 25 mL 3.86% glucose PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell (WBC) count, ultrafiltration (UF) volume, and morphology change in parietal peritoneum were examined. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, both p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, all p < 0.05). Peritoneal rest had some advantages in UF failure and WBC count only (both p < 0.05). However, rosiglitazone was more effective than peritoneal rest for vascularity and peritoneal thickness (p < 0.05). We suggest that the PPAR agonist rosiglitazone may have a therapeutic value in the management of EPS by inhibiting inflammation and neovascularization.