PERITONEAL INFLAMMATION AFTER TWENTY-WEEK EXPOSURE TO DIALYSIS SOLUTION: EFFECT OF SOLUTION VERSUS CATHETER-FOREIGN BODY REACTION

Background: We hypothesized that both sterile solutions and foreign body reaction to the peritoneal dialysis catheter are associated with inflammatory changes in rats exposed to hypertonic solution. Methods: Four hypertonic solutions (30 - 40 mL) were injected daily via needle and syringe over 20 weeks in 4 groups of rats: 4.25% standard clinical solution (LAC), LAC plus pyridoxamine (PYR), LAC plus ethyl pyruvate (EP), and a biocompatible 4% dextrose solution (BIC). Two groups received catheters: a non-injected 4-week catheter group (C4) and a group injected for 20 weeks with the BIC solution (CI). Control animals (CON) were not injected. In the C4 group, adherent cells were separated from the catheter and examined by culture and electron microscopy to ensure that animals were bacteria free prior to exposure to solution. Animals underwent transport experiments to determine mass transfer coefficients of mannitol (MTC(M)) and albumin (MTC(A)), osmotic filtration flux (J(osm)), and hydrostatic pressure-driven flux (J(p)). After euthanasia, tissues were examined for submesothelial thickness, vascular density, and immunohistochemistry for various cytokines. Results: The catheter cell layer was free of bacteria and consisted of macrophages, lymphocytes, mesothelial cells, and fibroblastic cells. Marked differences in angiogenesis and submesothelial thickening were noted for the catheter groups. Transport differences were mixed: MTC(M) was significantly less for the CI group and MTC(A) was variable among the groups. There were no differences among groups for J(osm) or J(p). Inflammatory markers in the catheter-adherent cells correlated with inflammatory changes in the tissue. These data demonstrate significant changes in submesothelial thickness, angiogenesis, transport function, and inflammatory markers between animals injected with sterile solutions over 20 weeks with and without catheters. Conclusion: An indwelling catheter amplifies peritoneal inflammation from dialysis solutions through a foreign body reaction. Our data also suggest that additives to existing solutions may have limited the effect on inflammatory response to non-biocompatible solutions.