Immunopathological changes in a uraemic rat model for peritoneal dialysis.
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.
Zareie
Mohammad
M
Department of Molecular Cell Biology, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
De Vriese
An S
AS
Hekking
Liesbeth H P
LH
ter Wee
Piet M
PM
Schalkwijk
Casper G
CG
Driesprong
Bas A J
BA
Schadee-Eestermans
Inge L
IL
Beelen
Robert H J
RH
Lameire
Norbert
N
van den Born
Jacob
J
D000818:Animals; D015314:Dialysis Solutions / Q000494:pharmacology*; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009392:Nephrectomy; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D015314:Dialysis Solutions; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators