Original Report: Laboratory Investigation

Role of Cellular Cholesterol in Pharmacologic Preconditioning with Cyclosporine in Experimental Kidney Transplantation
Fuad S. Shihab^a, William M. Bennett^b, Takeshi F. Andoh<sup>c

a</sup>Division of Nephrology, University of Utah School of Medicine, Salt Lake City, Utah, and
^bSolid Organ and Cellular Transplant Services, Legacy Good Samaritan Hospital, and
^cDivision of Liver and Pancreas Transplantation, Oregon Health and Sciences University, Portland, Oreg., USA

Address of Corresponding Author

Am J Nephrol 2010;31:134-140 (DOI: 10.1159/000259900)

  Key Words

• Cholesterol
• Cyclosporine
• Ischemia reperfusion injury
• Kidney transplantation
• Statin
• Syngeneic

  Abstract

Background/Aims: Ischemia reperfusion injury in the early posttransplant period affects immediate graft function and late allograft dysfunction. Recently, we showed that pharmacologic preconditioning with a calcineurin inhibitor improved transplant outcomes in rat syngeneic kidney transplantation. There is also evidence that cellular cholesterol content increases after many types of renal injury. Methods: In this study, we looked at the effect of cyclosporine (CsA) on the donor kidney free cholesterol (FC) content in this model. Donor rats were pretreated with one dose of CsA 10 mg/kg administered 24 h or 7 days before being subjected to 2 h cold ischemia and then transplanted. Results: Pharmacologic preconditioning with CsA significantly improved renal function and histology and increased donor kidney FC content. On the other hand, fluvastatin co-administration with CsA abrogated that beneficial effect in association with a decrease in donor kidney FC content. Conclusion: CsA preconditioning leads to better outcomes in kidney transplantation and is associated with up-regulation of renal FC content. The latter may then contribute to acquired cytoresistance, possibly by stabilizing the plasma membrane. Thus, use of statins around the time of transplantation may need to be evaluated until further studies are conducted to determine the clinical relevance of this observation.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Fuad S. Shihab, MD
University of Utah School of Medicine, Division of Nephrology
Room 4R312, 30 North 1900 East
Salt Lake City, UT 84132 (USA)
Tel. +1 801 581 6709, Fax +1 801 581 4343, E-Mail Fuad.Shihab@hsc.utah.edu

  Article Information

Received: September 3, 2009
Accepted: October 9, 2009
Published online: November 17, 2009
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 1, Number of References : 28