Skip Navigation


NDT Advance Access originally published online on September 5, 2007
Nephrology Dialysis Transplantation 2008 23(1):110-119; doi:10.1093/ndt/gfm563
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
23/1/110    most recent
gfm563v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in NDT
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ozaki, T.
Right arrow Articles by Matsuo, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ozaki, T.
Right arrow Articles by Matsuo, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Intrarenal administration of recombinant human soluble thrombomodulin ameliorates ischaemic acute renal failure

Takenori Ozaki1, Chabouk Anas1,2, Shoichi Maruyama1, Tokunori Yamamoto2, Kaoru Yasuda1, Yoshiki Morita1, Yasuhiko Ito1, Momokazu Gotoh2, Yukio Yuzawa1 and Seiichi Matsuo1

1Department of Nephrology and 2Department of Urology, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showaku, Nagoya, Japan 466-8550, Japan

Correspondence to: Dr Shoichi Maruyama, MD, Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showaku, Nagoya, Japan 466-8550, Japan. Email: marus{at}med.nagoya-u.ac.jp



  Abstract

Background. Thrombomodulin (TM) is an endothelial anti-coagulant cofactor which also has anti-inflammatory properties. The present study was performed to investigate the effects of recombinant human soluble TM (RHS-TM) on ischaemia/reperfusion (I/R) renal injury.

Methods. A right nephrectomy was performed in rats, and the left kidney was filled with RHS-TM (0.25 mg/kg), argatroban (20 mg/kg) or a vehicle for 45 min. Before reperfusion, the fluid trapped in the kidney was completely removed. At 24 h after I/R, renal cortical blood flow was measured using a CCD video camera, and the kidneys were harvested for the study. Next, cultured human umbilical vein endothelial cells were treated with RHS-TM (2, 10 or 50 mg/ml) or a vehicle, and incubated for 5 h in culture medium containing 300 µM hydrogen peroxide. Apoptotic cell death was analysed by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay.

Results. Immunohistochemistry revealed that the level of TM expression decreased in rat kidneys after I/R. RHS-TM significantly decreased blood urea nitrogen and serum creatinine levels. It also prevented a reduction in cortical blood flow, and attenuated tubular damage and macrophage/neutrophil infiltration. In addition, the number of TUNEL-positive cells decreased significantly in rats treated with RHS-TM. In contrast, argatroban, an inhibitor of thrombin did not show significant renoprotective actions. The results of in vitro study showed that RHS-TM significantly suppressed the number of apoptotic cells.

Conclusion. The transient intrarenal administration of RHS-TM, but not argatroban, to the kidney attenuates I/R renal injury. The present study suggests that RHS-TM would be a useful tool in preventing transplanted kidney damage or treating acute renal failure in the clinical setting.

Keywords: apoptosis; blood flow; endothelium; ischaemia; thrombomodulin

Received for publication: 22. 8.06
Accepted in revised form: 24. 7.07


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?

Related articles in NDT:

In this issue ...

NDT 2008 23: i. [Extract] [FREE Full Text]  



This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
A. A. Sharfuddin, R. M. Sandoval, D. T. Berg, G. E. McDougal, S. B. Campos, C. L. Phillips, B. E. Jones, A. Gupta, B. W. Grinnell, and B. A. Molitoris
Soluble Thrombomodulin Protects Ischemic Kidneys
J. Am. Soc. Nephrol., March 1, 2009; 20(3): 524 - 534.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.