Journal Article

Lipid‐lowering‐independent effects of simvastatin on the kidney in experimental hypercholesterolaemia

Stephanie H. Wilson, Alejandro R. Chade, Ariel Feldstein, Tatsuya Sawamura, Claudio Napoli, Amir Lerman and Lilach O. Lerman

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue 4, pages 703-709
Published in print April 2003 | ISSN: 0931-0509
Published online April 2003 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfg143
Lipid‐lowering‐independent effects of simvastatin on the kidney in experimental hypercholesterolaemia

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Background. Hypercholesterolaemia (HC), an independent risk factor for renal injury, is associated with formation of oxidized low‐density‐lipoprotein (ox‐LDL), increased oxidative‐stress and renal inflammation. HMG‐CoA‐reductase inhibitors are commonly used in HC, but their effects on renal haemodynamics and function in HC are poorly understood.

Methods. Pigs were studied after a 12‐week normal diet, a 2% high‐cholesterol diet (HC) or an HC diet supplemented with simvastatin (HC+simvastatin, 80 mg/day) (n=6–8 each group). Renal haemodynamics and function were quantified in vivo with electron‐beam computed tomography (EBCT). Shock‐frozen renal tissue was subsequently studied using immunohistochemistry.

Results. LDL cholesterol was similarly increased in HC and HC+simvastatin. Simvastatin‐treated animals showed increased expression of endothelial nitric‐oxide‐synthase (eNOS), and decreased expression of the ox‐LDL receptor LOX‐1 in renal endothelial cells. Simvastatin also decreased tubular immunoreactivity of inducible‐NOS, nitrotyrosine, nuclear‐factor‐κB, and tubuloglomerular trichrome staining. These were associated with a significant increase in cortical (6.1±0.1 vs 5.0±0.3 and 5.0±0.1 ml/min/cc, respectively, P<0.001) and medullary perfusion in HC+simvastatin compared to normal and HC.

Conclusions. Simvastatin attenuated the inflammatory and pro‐oxidative environment as well as fibrosis in kidneys in pigs with diet‐induced HC, in association with enhanced renal perfusion. These cholesterol‐lowering‐independent changes imply novel renoprotective effects of statins in the setting of HC and atherosclerosis.

Keywords: HMG‐CoA reductase inhibitors; hypercholesterolaemia; kidney

Journal Article.  3497 words.  Illustrated.

Subjects: Nephrology

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