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NDT Advance Access published online on August 7, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp384
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© The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Celecoxib treatment reduces peritoneal fibrosis and angiogenesis and prevents ultrafiltration failure in experimental peritoneal dialysis

Paolo Fabbrini1,2, Margot N. Schilte2, Mammad Zareie2, Piet M. ter Wee3, Eelco D. Keuning2, Robert H. J. Beelen2 and Jaap van den Born2,4

1 Clinica Nefrologica, Ospedale San Gerardo, Monza, Italy 2 Department Molecular Cell Biology and Immunology, VU University Medical Center 3 Department of Nephrology, VU University Medical Center, Amsterdam 4 Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands

Correspondence and offprint requests to: Margot N. Schilte; E-mail: m.schilte{at}vumc.nl



  Abstract

Background. Daily peritoneal exposure to peritoneal dialysis fluid (PDF) induces severe morphological alterations including fibrosis and angiogenesis that lead to a loss of peritoneal ultrafiltration (UF) capacity. Since cyclooxygenase (COX)-2 is involved in fibrosis and angiogenesis, we investigated the in vivo effects of a selective COX-2 inhibitor (celecoxib) in a rat-PD model.

Methods. Sixteen rats daily received 10 ml of conventional PDF for 4–5 weeks intraperitoneally. Half of them (n = 8) daily received celecoxib (20 mg/kg BW) via oral gavage, and the other half (n = 8) received vehicle via oral gavage. The study also included two control groups (no PDF instillations), each consisting of n = 8 animals that daily received celecoxib or vehicle, respectively, via oral gavage. Functional, morphological and cellular parameters were analysed.

Results. PDF exposure induced an inflammatory condition evidenced by the increased leucocyte number and synthesis of MCP-1, VEGF and hyaluronic acid. After PDF exposure, the omentum showed intense angiogenesis and milky spots formation. Parietal peritoneum showed increased angiogenesis, lymphangiogenesis, submesothelial matrix thickness and enhanced expression of mesothelial aquaporin1 (Aqp1). Concomitant PDF and celecoxib exposure drastically reduced PGE2 levels, angiogenesis, lymphangiogenesis, fibrosis and milky spot formation in studied tissues, but did not modify mesothelial Aqp1 expression nor the tissue expression of VEGF and inflammatory markers. PDF exposure induced severe UF failure that celecoxib treatment completely prevented.

Conclusions. Altogether, celecoxib treatment improves UF capacity and reduces morphological alterations in our rat PD model.

Keywords: angiogenesis; celecoxib; fibrosis; peritoneal dialysis; ultrafiltration failure

Received for publication: 23. 6.08
Accepted in revised form: 7. 7.09


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