Role of cellular cholesterol in pharmacologic preconditioning with cyclosporine in experimental kidney transplantation.
OBJECTIVE
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.


CONCLUSIONS
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.
Shihab
Fuad S
FS
Division of Nephrology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. Fuad.Shihab@hsc.utah.edu
Bennett
William M
WM
Andoh
Takeshi F
TF
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D000077340:Fluvastatin; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000293:injuries; D007672:Kidney Cortex; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007166:Immunosuppressive Agents; D007211:Indoles; D000077340:Fluvastatin; D016572:Cyclosporine; D002784:Cholesterol