Effects of Peritoneal Rest on Peritoneal Fibrosis in CAPD Rats

Nam, Jick Hwa; Kim, Yong Lim; Kim, Chan Duck; Kim, Seog Jae; Kim, Sung Ho; Kim, Jun Hong; Cho, Dong Kyu; Kim, Yong Jin

Abstract

Ultrafiltration failure has been known as a major cause of dropout from long-term peritoneal dialysis and is often related to peritoneal hyperpermeability. This can be explained in part by progressive peritoneal fibrosis. The present experiment has been undertaken to evaluate the effects of peritoneal rest on peritoneal transport and morphology in rat model of peritoneal dialysis. Twenty-four male rats(Sprague-Dawley, 250-300g) were used and divided into three groups : group 1 (control, n=6) without dialysis, group 2(n=9) sacrificed immediately after 3 weeks of dialysis, and group 3 (n=9) sacrificed after 4 weeks of peritoneal rest after 3 weeks of dialysis. Peritoneal dialysis was performed twice a day with 25mL of 3.86% dextrose solution for 3 weeks. Peritonitis was induced by supplementing lipopolysaccharide(5 microgram/mL) in the dialysis fluid on days 8, 10 and 12 of peritoneal dialysis. Peritoneal equilibration tests were performed before dialysis and repeated on the 4th and 8th week of dialysis. Morphometric analysis of the peritoneal membrane and immunohistochemistry for collagen type I and type III were done in tissue specimens obtained at the time of sacrifice. The D/Do ratio for glucose at two hours in groups 2 and 3 at the beginning of week 4 were significantly lower than baseline value, indicating increase in the peritoneal penneability to glucose after 3 weeks of dialysis. D/Do in group 3 at the beginning of week 8, after 4 weeks of peritoneal rest, was significantly higher than at week 4. The drained dialysate volumes in groups 2 and 3 at week 4 were significantly lower than at baseline; however, The drained dialysate volume in group 3 at week 8 was significantly greater than at week 4. The thickness of the parietal peritoneal membraoe in group 2 and 3 were significantly greater than in group 1. Severity of the thickness of the parietal peritoneal membrane in group 3 was not much than that of group 2(group 1, 11.4+/-7.6; group 2, 37.5+/-18.4; group 3, 21.4+/-12.1 micromiter). Histologically, the thickened peritoneum in group 2 showed a monolayer of mesothelial cells and under-lying multilayer of curled collagen bundles. Mononuciear cells and fibroblasts were embedded in these collagen layers and capillary proliferation was present. Immunohistochemistry for collagen type I and Z demonstrated that the distribution of collagen type llI was richer than that of collagen l in group 2 at fibrotic area of submesothelial region. These findings were decreased in group 3. Ultrastructural examination of the peritoneum showed thicker fibrotic zone and the activated fibroblasts in group 2 compared to group 1 and 3. Meso-thelial cells were plump and the number of mesothelial microvilli was decreased in group 2. Nucleus was enlarged and irregular. Intracytoplasmic orga-nelles were also richer than those of group I or 3. In conclusion, peritoneal rest improves ultrafiltration in rats by decreasing the hyperpermeability of glucose and also reduces the degree of peritoneal fibrosis. These data suggest that dialysis-induced changes in peritoneal transport and morphology are reversible under the condition of peritoneal rest in this experimental model.