BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. OBJECTIVE: To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). METHODS: 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 - 3 weeks) + peritoneal resting (4 - 6 weeks); C-R group, CG (0 - 3 weeks) + 1 mg/L colchicine (4 - 6 weeks); C-P group, CG (0 - 3 weeks) + 1 mg/L colchicine in drinking water (0 - 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. RESULT: Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. CONCLUSION: We suggest that colchicine may have therapeutic value in the management of EPS.
BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. OBJECTIVE: To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPSrat model in both progression (P) and regression (R). METHODS: 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 - 3 weeks) + peritoneal resting (4 - 6 weeks); C-R group, CG (0 - 3 weeks) + 1 mg/L colchicine (4 - 6 weeks); C-P group, CG (0 - 3 weeks) + 1 mg/L colchicine in drinking water (0 - 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. RESULT: Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. CONCLUSION: We suggest that colchicine may have therapeutic value in the management of EPS.
Authors: Rajesh M Jagirdar; Andreas Bozikas; Sotirios G Zarogiannis; Maria Bartosova; Claus Peter Schmitt; Vassilios Liakopoulos Journal: Int J Mol Sci Date: 2019-11-16 Impact factor: 5.923