NDT Advance Access published online on June 5, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm168
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Renal protective effects of pitavastatin on spontaneously hypercholesterolaemic Imai Rats
1Department of Nephrology, Qilu Hospital of Shandong University, Shandong Province, China, 2Department of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama, Japan, 3Teaching Hospital of Shandong University of Traditional Chinese Medicine, Shandong Province, China, 4Ryoshukai Wakayama Kidney Disease Clinic, Wakayama, Japan, 5Department of Nutrition, Siebold University of Nagasaki, Nagasaki, Japan and 6Department of Nephrology, Showa University School of Medicine, Tokyo, Japan
Correspondence and offprint requests to: Haruhisa Otani MD PhD, Wakayama Kidney Disease Clinic, San Ei Building 5F, 5-1-8 Misono Cho, Wakayama City 640-8331, Japan. Email: hotani{at}wakayama-med.ac.jp
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Abstract |
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Background. Independent of their lipid-lowering effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have renal protective effects on various models of progressive renal diseases, therefore, additional therapeutic advantages have been considered. In the present study, using spontaneously hypercholesterolaemic Imai rats, we examined the protective effects of pitavastatin on renal injuries and the oxidative modification of the low-density lipoprotein (LDL) and high-density lipoprotein (HDL), since oxidized lipoproteins are speculated to be involved in the mechanism of this rat strain's renal injuries.
Methods. Male Imai rats were treated with pitavastatin (n = 11) at a dose of 100 mg/kg diet or received no specific therapy as controls (n = 11) from 10 to 22 weeks of age. Body weight, urinary protein excretion and serum constituents were evaluated every 4 weeks. At the end of the study, the effects of pitavastatin on the susceptibility of serum LDL and HDL to oxidation, and renal histology were examined.
Results. Pitavastatin treatment did not affect hyperlipidaemia, but significantly reduced proteinuria and preserved creatinine clearance deterioration. At the end of the study, lag times for LDL and HDL oxidation were prolonged by the treatment of pitavastatin to 126 and 153%, respectively, compared with the controlled group. The glomerulosclerosis index (SI) for untreated controlled rats was significantly higher than that for the pitavastatin-treated group. An immunohistochemistry study showed significantly lower numbers of ED-1 positive macrophages in the glomeruli and interstitium in pitavastatin-treated rats compared with those controlled.
Conclusion. Pitavastatin treatment prevented renal injuries in Imai rats independent of lipid-lowering effects. Prevention of oxidative modification of LDL and HDL may play an important role on the beneficial effects of pitavastatin treatment.
Keywords: hyperlipidaemia; Imai rat; lipoprotein; oxidative modification; pitavastatin
Received for publication: 6.12.05
Accepted in revised form: 5. 3.07