Protective effect of HMG-CoA reductase inhibitor on experimental renal ischemia-reperfusion injury.
BACKGROUND
Increasing evidence supports an important role for inflammation in the pathogenesis of renal ischemia-reperfusion injury (IRI). Recently, HMG-CoA reductase inhibitors, 'statins', have demonstrated anti-inflammatory effects independent of cholesterol-lowering.


OBJECTIVE
We tested the hypothesis that a statin would improve outcome in a murine model of renal IRI. Upon finding a protective effect, we tested the hypothesis that the mechanisms by which statins protected in renal IRI was by reducing neutrophil and macrophage infiltration and upregulating the anti-inflammatory cytokine IL-6.


METHODS
Cerivastatin at various dosing regimens was administered to NIH Swiss mice to evaluate the effects on renal IRI. Analysis of renal structure, function, neutrophil and macrophage infiltration, cytokine production, as well as mortality was performed in cerivastatin- and saline-treated groups.


RESULTS
PRIMARY: Cerivastatin pretreatment for 3 days led to a significant improvement in renal function, tubular injury as well as survival after IRI compared to saline-treated mice. SECONDARY: Neutrophil and macrophage infiltration into kidney tissue was similar in both groups. IL-6 was markedly upregulated early in the kidneys of statin-treated compared to saline-treated mice.


CONCLUSIONS
These data demonstrate that a statin compound can improve the course of ischemic acute renal failure. Induction of protective molecules such as IL-6 may underlie this effect.
Yokota
Noako
N
Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Md 21205, USA.
O'Donnell
Michael
M
Daniels
Frank
F
Burne-Taney
Melissa
M
Keane
William
W
Kasiske
Bertram
B
Rabb
Hamid
H
D000818:Animals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D051379:Mice; D011725:Pyridines / Q000494:pharmacology*; D015427:Reperfusion Injury
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin