PMID- 15840671 OWN - NLM STAT- MEDLINE DCOM- 20051006 LR - 20171116 IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 20 IP - 7 DP - 2005 Jul TI - Immunopathological changes in a uraemic rat model for peritoneal dialysis. PG - 1350-61 AB - BACKGROUND: Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Both the uraemic state of these patients and chronic exposure to PD fluid are associated with the development of functional and structural alterations of the peritoneal membrane. In a well-established chronic PD rat model, we compared rats with normal renal function with subtotal nephrectomized rats that developed uraemia. METHODS: Uraemic and control rats received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters during a 6 week period. Uraemic and control rats receiving no PD fluid served as controls. Parameters relevant for peritoneal defence and serosal healing responses were analyzed. RESULTS: Uraemic animals were characterized by 2-3-fold increased serum urea and creatinine levels, accompanied by a significantly reduced haematocrit. Uraemia (without PD fluid exposure) induced new blood vessels in different peritoneal tissues, accompanied by increased accumulation of advanced glycation end products (AGEs) and elevated levels of angiogenic factors such as vascular endothelial growth factor and monocyte chemoattractant protein-1 (MCP-1) in peritoneal lavage fluid. A much stronger peritoneal response was observed upon PD fluid exposure in non-uraemic rats. This included the induction of angiogenesis and fibrosis in various peritoneal tissues, accumulation of AGEs, immunological activation of the omentum, damage to the mesothelial cell layer, focal formation of granulation tissues and increased MCP-1 and hyaluronan levels in peritoneal lavage fluid. Finally, chronic PD fluid instillation in uraemic rats did not induce an additional peritoneal response compared to PD fluid exposure in non-uraemic rats, except for the degree of AGE accumulation. CONCLUSIONS: Both uraemia and PD fluid exposure result in pathological alterations of the peritoneum. However, uraemia did not induce major additive effects to PD fluid-induced injury. These results substantially contribute to the understanding of the pathobiology of the peritoneum under PD conditions. FAU - Zareie, Mohammad AU - Zareie M AD - Department of Molecular Cell Biology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. FAU - De Vriese, An S AU - De Vriese AS FAU - Hekking, Liesbeth H P AU - Hekking LH FAU - ter Wee, Piet M AU - ter Wee PM FAU - Schalkwijk, Casper G AU - Schalkwijk CG FAU - Driesprong, Bas A J AU - Driesprong BA FAU - Schadee-Eestermans, Inge L AU - Schadee-Eestermans IL FAU - Beelen, Robert H J AU - Beelen RH FAU - Lameire, Norbert AU - Lameire N FAU - van den Born, Jacob AU - van den Born J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050419 PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Dialysis Solutions) RN - 0 (Glycation End Products, Advanced) RN - 0 (Inflammation Mediators) SB - IM MH - Animals MH - Dialysis Solutions/*pharmacology MH - Disease Models, Animal MH - Epithelium/drug effects MH - Glycation End Products, Advanced/metabolism MH - Inflammation Mediators/metabolism MH - Leukocytes/drug effects MH - Male MH - Neovascularization, Physiologic/drug effects MH - Nephrectomy MH - *Peritoneal Dialysis MH - Peritoneum/*drug effects/metabolism/pathology MH - Rats MH - Rats, Wistar MH - Uremia/*immunology/metabolism/*pathology EDAT- 2005/04/21 09:00 MHDA- 2005/10/07 09:00 CRDT- 2005/04/21 09:00 PHST- 2005/04/21 09:00 [pubmed] PHST- 2005/10/07 09:00 [medline] PHST- 2005/04/21 09:00 [entrez] AID - gfh835 [pii] AID - 10.1093/ndt/gfh835 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2005 Jul;20(7):1350-61. doi: 10.1093/ndt/gfh835. Epub 2005 Apr 19.