Abstract
Previous studies have reported that statins suppress the progression of chronic kidney disease (CKD). The effects are independent of lowering serum cholesterol and could be different for each statin. Statins do not change serum cholesterol levels in rats. We administered pitavastatin into a CKD rat model to confirm the renoprotective effect of pitavastatin without lowering cholesterol. We prepared the CKD rat by removing 2/3 of the left kidney and the whole right kidney, and randomly dividing the kidney into the pitavastatin treatment group (n = 7) or the no treatment group (n = 7). Pitavastatin was administered by gavages at 3mg/kg/day for 12 weeks. At the end of the experiment a remnant of the kidney was removed to evaluate pathological changes and quantitative real-time PCR (qPCR). There were no differences in diet intake, body weight, and serum lipid profiles between the two groups. However, pitavastatin treatment diminished serum creatinin elevation (1.1 ± 0.8 vs. 1.9 ± 0.7mg/dl) and creatinin-clearance depletion (23 ± 7 vs. 13 ± 4ml/min/g). The pitavastatin group showed suppression for urine protein (175 ± 45 vs. 273 ± 35mg/ml·Cre) and albumin (968 ± 95 vs. 1483 ± 214μg/ml·Cre). Microscope pitavastatin treatment ameliorated the glomerular sclerosis index score (2.5 ± 0.4 vs. 3.2 ± 0.4) and interstitial fibrosis score (24.3 ± 3.8 vs. 34.8 ± 5.8) in the remnant kidney. By qPCR the expression of TGF-β and CTGF mRNA were suppressed by pitavastatin. The pathological changes were significantly correlated with serum creatinin, creatinin-clearance, urine protein, urine albumin, and the mRNA expression of TGF-β and CTGF. We confirmed that pitavastatin had a renoprotective effect without changing serum lipid profiles. The changes may be induced by the suppression of TGF-β and CTGF through the pleiotrolic effect of pitavastain.
