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Original Paper

Everolimus Retards Cyst Growth and Preserves Kidney Function in a Rodent Model for Polycystic Kidney Disease

Wu M.a · Wahl P.R.a · Le Hir M.b · Wäckerle-Men Y.a · Wüthrich R.P.a, c · Serra A.L.a, c

Author affiliations

aPhysiological Institute and bAnatomical Institute, University Zürich Irchel, and cClinic for Nephrology, University Hospital, Zürich, Switzerland

Related Articles for ""

Kidney Blood Press Res 2007;30:253–259

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 19, 2007
Accepted: May 18, 2007
Published online: June 27, 2007
Issue release date: July 2007

Number of Print Pages: 7
Number of Figures: 6
Number of Tables: 0

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: http://www.karger.com/KBR

Abstract

Background/Aims: Rapamycin inhibits cyst growth in polycystic kidney disease by targeting the mammalian target of rapamycin (mTOR). To determine if this is a class effect of the mTOR inhibitors, we examined the effect of everolimus, the analogue of rapamycin, on disease progression in the Han:SPRD rat model of polycystic kidney disease. Methods: Four-week-old male heterozygous cystic (Cy/+) and wild-type normal (+/+) Han:SPRD rats were administered everolimus or vehicle (3 mg/kg/day) by gavage for 5 weeks. Kidney function and whole-blood trough levels of everolimus were monitored. After treatment kidney weight and cyst volume density were assessed. Tubule epithelial cell proliferation was assessed by BrdU staining. Results: Everolimus trough levels between 5 and 7 µg/l were sufficient to significantly reduce kidney and cyst volume density by approximately 50 and 40%, respectively. The steady decrease of kidney function in Cy/+ rats was reduced by 30% compared with vehicle-treated Cy/+ rats. Everolimus treatment markedly reduced the number of 5-bromo-2-deoxyuridine-labeled nuclei in cyst epithelia. Body weight gain and kidney function were impaired in everolimus-treated wild-type rats. Conclusion: Moderate dosage of everolimus inhibits cystogenesis in Han:SPRD rats. The inhibitory effect of everolimus appears to represent a class effect of mTOR inhibitors.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 19, 2007
Accepted: May 18, 2007
Published online: June 27, 2007
Issue release date: July 2007

Number of Print Pages: 7
Number of Figures: 6
Number of Tables: 0

ISSN: 1420-4096 (Print)
eISSN: 1423-0143 (Online)

For additional information: http://www.karger.com/KBR


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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