Glucose and mannitol have different effects on peritoneal morphology in chronically dialyzed rats

In previous studies, we showed that glucose reduces the morphologic changes in rat peritoneum caused by chronic intraperitoneal administration of 0.9% NaCl solution. In the present study, we set out to determine if the observed results were attributable to hyperosmolarity or to the metabolic effect of the glucose. Intraperitoneal catheters were implanted in 19 rats. The animals were then intraperitoneally exposed twice daily for 30 days to 20 mL 0.9% saline supplemented with either 250 mmol/L glucose (GLU, n = 9) or 250 mmol/L mannitol (MAN, n = 10). Control rats did not undergo catheter implantation or the dialysis procedure (CON, n = 6). At the end of the study, a 1-hour peritoneal equilibration test (PET) using Dianeal 3.86% (Baxter Healthcare SA, Castlebar, Ireland) was performed in every dialyzed rat to analyze peritoneal transport. Afterward, the rats were humanely killed by bleeding, and a semi-quantitative scale was used to evaluate adhesions in the peritoneal cavity. Imprints of the visceral mesothelium and samples of the visceral peritoneum (liver) were then taken and analyzed by light microscopy. The PET results for glucose, urea, creatinine, and total protein were comparable in both experimental groups. We found that intraperitoneal adhesions were more severe in the MAN group (6 rats with adhesions graded > 3) than in the GLU group (only 1 such rat). No difference in peritoneal thickness was observed between the experimental groups (MAN: 54.9 +/- 17.8 microns; GLU: 51.2 +/- 14.5 microns); however, in both experimental groups, the thickness was greater than in the CON group (3.9 +/- 0.6 microns). The density of the peritoneal blood vessels tended to be greater in the MAN group than in the GLU group (0.158 +/- 0.072 vessels/1000 microns 2 vs. 0.085 +/- 0.067 vessels/1000 microns 2, p = 0.0541). No visible blood vessels were evident in the CON group. The density of mesothelial cells was higher in the MAN group than in the GLU group (2456 +/- 333 cells/mm 2 vs. 2090 +/- 322 cells/mm 2, p < 0.05), and, in both experimental groups, the cell density was higher than in the CON group (817 +/- 100 cells/mm 2, p < 0.01). The nucleus: cytoplasm area ratio in mesothelial cells was comparable in the MAN and GLU groups (0.206 +/- 0.039 and 0.176 +/- 0.045), but that ratio was higher in both experimental groups than in the CON group (0.086 +/- 0.010, p < 0.01). We conclude that glucose-induced changes in the peritoneum of rats exposed to chronic peritoneal dialysis depend on both osmotic and metabolic effects.