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The Effects of Atorvastatin on the Pogression of Metabolic Syndrome Associated Kidney Renal Disease
Author(s) -
Taylor Lateia,
Fizer Brianca,
McPherson Kasi,
Williams Jan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.964.4
Subject(s) - atorvastatin , proteinuria , medicine , endocrinology , blood pressure , kidney , kidney disease , metabolic syndrome , strain (injury) , leptin receptor , nephrology , leptin , obesity
We recently created a 16 base pair frame‐shift deletion in exon 11 of the leptin receptor gene within the genetic background of the Dahl SS rat (SS LepR ‐/‐ strain) using Zinc‐finger nucleases that develops many characteristics of metabolic syndrome (MetS) along with progressive kidney disease. The kidneys from the SS LepR ‐/‐ strain displayed increased lipid accumulation compared to their control counterparts (SS WT ). Lipid lowering drugs such as statins have proven to be renoprotective in various models of kidney disease. Therefore, the purpose of this study was to evaluate the impact of atorvastatin on the progression of renal disease in the SS LepR ‐/‐ strain. Atorvastatin was given orally for 28 days at a dose of 10 mg/kg/day in 10 week‐old SS LepR ‐/‐ rats with pre‐existing renal injury. Treatment with atorvastatin reduced serum cholesterol levels by 42% over the course of the study. After 14 days, MAP (via tailcuff) and proteinuria increased to 157±10 mmHg and 464±49 mg/day, respectively, in vehicle treated rats. While we did not observe any differences in MAP after 14 days of treatment with atorvastatin (144±8 mmHg), proteinuria decreased by 28% (333±28 mg/day). After 28 days of atorvastatin treatment, MAP and proteinuria was reduced by 18% and 51%, respectively, in comparison to vehicle treated rats. In conclusion, these data suggest that early treatment with atorvastatin delayed the development of severe proteinuria in the SS LepR ‐/‐ strain independent of changes in arterial pressure. However, further studies are needed to determine the mechanism of the early beneficial effects of statin therapy on the progression of kidney disease associated with MetS.This research was supported by NIGMS NIH P20GM104357 and AHA 12SDG9440034.