Journal Article

Immunopathological changes in a uraemic rat model for peritoneal dialysis

Mohammad Zareie, An S. De Vriese, Liesbeth H. P. Hekking, Piet M. ter Wee, Casper G. Schalkwijk, Bas A. J. Driesprong, Inge L. Schadee-Eestermans, Robert H. J. Beelen, Norbert Lameire and Jacob van den Born

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 20, issue 7, pages 1350-1361
Published in print July 2005 | ISSN: 0931-0509
Published online April 2005 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh835
Immunopathological changes in a uraemic rat model for peritoneal dialysis

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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.

Keywords: AGE; angiogenesis; fibrosis; peritoneal dialysis; rat; uraemia

Journal Article.  5681 words.  Illustrated.

Subjects: Nephrology

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