Skip Navigation



NDT Advance Access published online on July 5, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh948
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
20/10/2071    most recent
gfh948v1
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 Similar articles in this journal
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 Wegner, B.
Right arrow Articles by Geiger, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wegner, B.
Right arrow Articles by Geiger, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received April 15, 2004
Accepted May 18, 2005

Original Articles

Caspofungin is less nephrotoxic than amphotericin B in vitro and predominantly damages distal renal tubular cells

Binytha Wegner 1*, Patrick Baer 1, Stefan Gauer 1, Gerhard Oremek 2, Ingeborg A. Hauser 1, and Helmut Geiger 1

1 Department of Nephrology, J.W. Goethe-University Frankfurt, Germany
2 Department of Laboratory Chemistry, J.W. Goethe-University Frankfurt, Germany

* To whom correspondence should be addressed.
Binytha Wegner, E-mail: b.wegner{at}em.uni-frankfurt.de



  Abstract

Background. Caspofungin (CAS) has recently been approved for treatment of invasive aspergillosis. In clinical trials, CAS-induced nephrotoxicity was markedly less pronounced compared to amphotericin B (AmB). Nevertheless, in a recent trial, nephrotoxicity in CAS-treated patients was considerably more pronounced than in preceding studies. Therefore, the aim of this study was to assess toxic effects of CAS on human renal proximal and distal tubular epithelial cells (PTC and DTC) in vitro, and to compare them to those of AmB.

Methods. Cells were isolated from human kidney tissue, and exposed to clinically relevant concentrations of CAS and AmB for 24 h. Total DNA content and cell viability were determined by DAPI staining and a modified MTT assay. For testing of cytotoxicity, LDH activity was measured in cell culture supernatants. To assess apoptotic effects, AnnexinV-binding assay and DAPI staining for detection of fragmented DNA were performed.

Results. DTC were more vulnerable towards the antifungal agents than PTC. In contrast to AmB, cell-damaging effects of CAS were less severe. DAPI staining revealed slight and dose-dependent antiproliferative effects of CAS at concentrations reflecting relevant plasma levels. At these concentrations, cell viability, determined by MTT assay, was not decreased in PTC and DTC. LDH release was marginally increased in a dose-dependent manner; apoptosis was not detected. Nevertheless, at CAS concentrations reflecting potential tissue concentrations, cell damaging effects were considerably more pronounced.

Conclusion. Our results suggest that CAS is less nephrotoxic than AmB in vitro. The antiproliferative and cytotoxic effects of CAS predominantly affect DTC, which seem to be more susceptible to CAS-induced damage.

Keywords: amphotericin B; caspofungin; in vitro; nephrotoxicity.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Med MicrobiolHome page
V. Yadav, R. Mandhan, Q. Pasha, S. Pasha, A. Katyal, A. K. Chhillar, J. Gupta, R. Dabur, and G. L. Sharma
An antifungal protein from Escherichia coli
J. Med. Microbiol., May 1, 2007; 56(5): 637 - 644.
[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.