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Renal protection by atorvastatin in a murine model of sickle cell nephropathy
Author(s) -
Zahr Rima S.,
Chappa Prasanthi,
Yin Hong,
Brown Lou A.,
Ataga Kenneth I.,
Archer David R.
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15157
Subject(s) - atorvastatin , albuminuria , nox4 , medicine , nephropathy , renal function , kidney , endocrinology , kidney disease , pharmacology , immunology , oxidative stress , nadph oxidase , diabetes mellitus
Summary 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.