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Bench |
Department of Molecular Cell Biology and Immunology,1 VU University Medical Center, Amsterdam, The Netherlands; Department of Molecular Biology,2 University Hospital La Princesa, Madrid, Spain; Department of Nephrology,3 VU University Medical Center, Amsterdam, The Netherlands a Now at Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
a Now at Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Correspondence to: M.N. Schilte, Department of Molecular Cell Biology and Immunology, H269, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. m.schilte{at}vumc.nl
Background: Peritoneal dialysis (PD) is associated with
functional and structural alterations of the peritoneal membrane, particularly
new vessel formation and fibrosis. In addition to anticoagulant effects,
heparin displays anti-inflammatory and angiostatic properties. Therefore, the
effects of administration of heparins on function and morphology of the
peritoneal membrane were studied in a rat PD model. Methods: Rats received 10 mL conventional PD fluid
(PDF) daily, with or without the addition of unfractionated heparin (UFH) or
low molecular weight heparin (LMWH) in the PDF (1 mg/10 mL intraperitoneally)
via a mini access port. Untreated rats served as controls. After 5 weeks, a
90-minute functional peritoneal transport test was performed and tissues and
peritoneal leukocytes were taken. Results: PD treatment induced loss of ultrafiltration
(p < 0.01), a twofold increase in glucose absorption (p
< 0.03), increased urea transport (p < 0.02), and loss of
sodium sieving (p < 0.03), which were also found in the PDF +
heparin groups. Increased peritoneal cell influx and hyaluronan production
(p < 0.02) as well as an exchange of mast cells and eosinophils
for neutrophils after PD treatment were observed in PD rats; addition of
heparin did not affect those changes. Mesothelial regeneration, submesothelial
blood vessel and matrix formation, and accumulation of tissue macrophages were
seen in PD animals. Spindle-shaped vimentin-positive and cytokeratin-negative
cells indicated either partial injury and denudation of mesothelial cells or
epithelial-to-mesenchymal transition. Neither UFH nor LMWH affected any of
these morphological changes. Conclusion: Within 5 weeks, PD treatment induces a
chronic inflammatory condition in the peritoneum, evidenced by high transport,
leukocyte recruitment, tissue remodeling, and induction of spindle-shaped
cells in the mesothelium. Addition of LMWH or UFH to the PDF did not prevent
these adverse PDF-induced peritoneal changes.
KEY WORDS: Angiogenesis; epithelial-to-mesenchymal transition; fibrosis; heparin; mesothelium; morphology; peritoneal transport.
Received 7 January 2008; accepted 1 May 2008.
This article has been cited by other articles:
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  P. Fabbrini, M. N. Schilte, M. Zareie, P. M. ter Wee, E. D. Keuning, R. H. J. Beelen, and J. van den Born Celecoxib treatment reduces peritoneal fibrosis and angiogenesis and prevents ultrafiltration failure in experimental peritoneal dialysis Nephrol. Dial. Transplant., December 1, 2009; 24(12): 3669 - 3676. [Abstract] [Full Text] [PDF]
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 M. N. Schilte, J. W.A.M Celie, P. M. t. Wee, R. H.J. Beelen, and J. van den Born FACTORS CONTRIBUTING TO PERITONEAL TISSUE REMODELING IN PERITONEAL DIALYSIS Perit. Dial. Int., November 1, 2009; 29(6): 605 - 617. [Abstract] [Full Text] [PDF]
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P. Margetts HEPARIN AND THE PERITONEAL MEMBRANE Perit. Dial. Int., January 1, 2009; 29(1): 16 - 19. [Full Text] [PDF]
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