Simvastatin protection against acute immune-mediated glomerulonephritis in mice

M. Christensen, A. W. Su, R. W. Snyder, A. Greco, J. H. Lipschutz, M. P. Madaio

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

In addition to cholesterol lowering, 3-hydroxy-3-nethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors limit inflammatory changes associated with atherosclerosis. There is also support for their use as inhibitors of progression in chronic renal disease, irrespective of cause. In this study, their capacity to limit acute renal inflammation was evaluated. For this purpose, mice were treated with Simvastatin either prior to, at the time of, or shortly after induction of nephrotoxic nephritis. The severity of disease was determined by evaluation of blood urea nitrogen (BUN), proteinuria, and renal histologic changes. The reversibility of benefit was evaluated by the administration of mevalonic acid along with nephrotoxic serum (NTS) and Simvastatin The severity of the acute nephritis, including proteinuria, elevated BUN, and histologic changes, was ameliorated in a dose-dependent manner, when Simvastatin was administered either prior to NTS injection or at the time of NTS injection. By contrast, Simvastatin did not alter the course of established nephritis. Coadministration of mevalonic acid, the immediate substrate following HMG-CoA reductase, abolished Simvastatin's renoprotective effect, indicating that the benefit is, at least in part, due to interference with HMG-CoA reductase and biosynthetic substrates downstream from the enzyme. These findings provide the rationale for the evaluation of the efficacy of HMG-CoA reductase inhibitors in patients with recurrent forms of renal inflammation, to limit the severity of acute exacerbations of disease, prevent renal scarring and slow the rate of progression.

Original languageEnglish (US)
Pages (from-to)457-463
Number of pages7
JournalKidney International
Volume69
Issue number3
DOIs
StatePublished - Feb 1 2006

Fingerprint

Simvastatin
Glomerulonephritis
Nephritis
Kidney
Hydroxymethylglutaryl CoA Reductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mevalonic Acid
Blood Urea Nitrogen
Proteinuria
Serum
Inflammation
Injections
Acute Disease
Coenzyme A
Chronic Renal Insufficiency
Cicatrix
Atherosclerosis
Cholesterol
Enzymes

Keywords

  • Anti-glomerular basement membrane
  • Glomerulonephritis
  • HMG-CoA reductase inhibitors
  • Inflammation

ASJC Scopus subject areas

  • Nephrology

Cite this

Christensen, M., Su, A. W., Snyder, R. W., Greco, A., Lipschutz, J. H., & Madaio, M. P. (2006). Simvastatin protection against acute immune-mediated glomerulonephritis in mice. Kidney International, 69(3), 457-463. https://doi.org/10.1038/sj.ki.5000086

Simvastatin protection against acute immune-mediated glomerulonephritis in mice. / Christensen, M.; Su, A. W.; Snyder, R. W.; Greco, A.; Lipschutz, J. H.; Madaio, M. P.

In: Kidney International, Vol. 69, No. 3, 01.02.2006, p. 457-463.

Research output: Contribution to journalArticle

Christensen, M, Su, AW, Snyder, RW, Greco, A, Lipschutz, JH & Madaio, MP 2006, 'Simvastatin protection against acute immune-mediated glomerulonephritis in mice', Kidney International, vol. 69, no. 3, pp. 457-463. https://doi.org/10.1038/sj.ki.5000086
Christensen M, Su AW, Snyder RW, Greco A, Lipschutz JH, Madaio MP. Simvastatin protection against acute immune-mediated glomerulonephritis in mice. Kidney International. 2006 Feb 1;69(3):457-463. https://doi.org/10.1038/sj.ki.5000086
Christensen, M. ; Su, A. W. ; Snyder, R. W. ; Greco, A. ; Lipschutz, J. H. ; Madaio, M. P. / Simvastatin protection against acute immune-mediated glomerulonephritis in mice. In: Kidney International. 2006 ; Vol. 69, No. 3. pp. 457-463.
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