Differential effect of statins on diabetic nephropathy in db/db mice

Recent studies suggest a potential benefit of the lipid-lowering medication in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although statins have been widely used to lower serum cholesterol levels, the effect of these drugs on diabetic nephropathy has not been fully elucidated. In the present study, therefore, we addressed the role of different kinds of statins on diabetic nephropathy in db/db mice. Mice were fed with a standard diet with 0.005% (w/w) of pitavastatin, rosuvastatin, and pravastatin for 8 weeks starting from 8 weeks of age. The treatment with statins did not affect the food intake, body weight gain, adiposity, or blood pressure in db/db mice. Treatment with statins also had no effect on plasma lipid levels. In terms of the effect on albuminuria, pitavastatin and rosuvastatin reduced the urinary excretion of albumin by 60 and 40%, respectively, but not pravastatin, suggesting the effect of these two drugs on diabetic nephropathy. Furthermore, pitavastatin and rosuvastatin improved glomerular hypertrophy. All statins treatment improved insulin resistance. In addition, rosuvastatin and pravastatin treatment reduced oxidative stress measured by urinary 8-OHdG level, whereas the statins had no effect on the inflammatory response in the kidney of db/db mice. These results are not consistent with the renoprotective effect of statins. In conclusion, our data suggest that pitavastatin and rosuvastatin can improve diabetic nephropathy through the suppression of glomerular hypertrophy, independent of lipid-lowering or anti-oxidative effects.