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Author Notes:

Correspondence: Rima S. Zahr, DO, Department of Pediatrics, Nephrology and Hypertension, 49 N. Dunlap Street, Suite 321, Memphis, TN 3801, USA, Tel: +1 802-233-9294, Fax: +1 901-287-4820, rzahr@uthsc.edu.

RSZ, KIA and DRA conceived and designed the present work.

RSZ performed the experiments, analysed data and wrote the first draft.

PC performed the research and analysed the data.

HY and LB analysed the data.

All authors approved the final version.

We thank Pfizer Inc. (New York, NY, USA) for providing atorvastatin via a compound transfer program.

We would also like to acknowledge the Children’s Healthcare of Atlanta and Emory University Pediatric Flow Cytometry and Biomarkers Cores.

KIA serves on clinical advisory boards of Global Blood Therapeutics and Novartis, and receives research support from Pfizer.

DRA receives research support from Agios Pharmaceuticals.

Subjects:

Research Funding:

This work was supported by NIH grant R01HL111659 (KIA, DRA).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • sickle cell disease
  • sickle cell nephropathy
  • oxidant stress
  • statins
  • albuminuria
  • ACUTE KIDNEY INJURY
  • MOUSE MODEL
  • OXIDATIVE STRESS
  • DISEASE
  • CHILDREN
  • ANEMIA
  • ALBUMINURIA
  • STATINS
  • PREVALENCE
  • BIOMARKERS

Renal protection by atorvastatin in a murine model of sickle cell nephropathy

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Journal Title:

British Journal of Haematology

Volume:

Volume 181, Number 1

Publisher:

, Pages 111-121

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Recent studies have demonstrated pleiotropic effects of statins in various mouse models of kidney disease. In this study, Townes humanized sickle cell mice were treated for 8 weeks with atorvastatin at a dose of 10 mg/kg/day starting at 10 weeks of age. Treatment with atorvastatin significantly reduced albuminuria, and improved both urine concentrating ability and glomerular filtration rate. Atorvastatin also decreased markers of kidney injury and endothelial activation, and ameliorated oxidant stress in renal tissues and peripheral macrophages. Atorvastatin downregulated the expression of mRNA levels of the NADPH oxidases, Cybb (also termed Nox2) and Nox4, which are major sources of oxidant stress in the kidney. These findings highlight the pleiotropic effects of atorvastatin and suggest that it may provide beneficial effects in sickle cell nephropathy.

Copyright information:

© 2018 John Wiley & Sons Ltd

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