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NDT Advance Access published online on October 4, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi138
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 11, 2005
Accepted August 12, 2005

Original Articles

Beneficial effects of aminoguanidine on peritoneal microcirculation and tissue remodelling in a rat model of PD

Mohammad Zareie 1*, Geert-Jan Tangelder 2, Piet M. ter Wee 3, Liesbeth HP Hekking 1, Anton A. van Lambalgen 2, Eelco D. Keuning 1, Inge L. Schadee-Eestermans 1, Casper G. Schalkwijk 4, Robert HJ Beelen 1, and Jacob van den Born 1

1 Departments of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands
2 Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands
3 Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands
4 Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands

* To whom correspondence should be addressed.
Mohammad Zareie, E-mail: m.zareie{at}vumc.nl



  Abstract

Background. The formation of glucose degradation products (GDPs) and accumulation of advanced glycation end products (AGEs) partly contribute to the bioincompatibility of peritoneal dialysis fluids (PDF). Aminoguanidine (AG) scavenges GDPs and prevents the formation of AGEs.

Methods. In a peritoneal dialysis (PD) rat model, we evaluated the effects of the addition of AG to the PDF on microcirculation and morphology of the peritoneum, by intravital microscopy and quantitative morphometric analysis.

Results. AG-bicarbonate effectively scavenged different GDPs from PDF. Daily exposure to PDF for 5 weeks resulted in a significant increase in leucocyte rolling in mesenteric venules, which could be reduced for ~50% by addition of AG-bicarbonate (P<0.02). Vascular leakage was found in rats treated with PDF/AG-bicarbonate, but not with PDF alone. Evaluation of visceral and parietal peritoneum showed the induction of angiogenesis and fibrosis after PDF instillation. PDF/AG-bicarbonate significantly reduced vessel density in omentum and parietal peritoneum (P<0.04), but not in mesentery. PDF-induced fibrosis was significantly reduced by AG (P<0.02). PDF instillation led to AGE accumulation in mesentery, which was inhibited by supplementation of AG. Since addition of AG-bicarbonate to PDF raised pH from 5.2 to 8.5, a similar experiment was performed with AG-hydrochloride that did not change the fluid acidity. We could reproduce most of the results obtained with AG-bicarbonate; however, AG-hydrochloride induced no microvascular leakage and had a minor effect on angiogenesis.

Conclusion. The supplementation of either AG reduced a number of PDF-induced alterations in our model, emphasizing the involvement of GDPs and/or AGEs in the PDF-induced peritoneal injury.

Keywords: aminoguanidine; angiogenesis; fibrosis; peritoneal dialysis; rats.
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