1.
Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner.
Nakamura, T, Sato, E, Fujiwara, N, Kawagoe, Y, Ueda, Y, Suzuki, T, Ueda, S, Fukami, K, Okuda, S, Yamagishi, S
Pharmacological research. 2010;(1):58-61
Abstract
Since co-administration of ezetimibe, a specific inhibitor of cholesterol absorption into the intestine, has been shown to augment lipid-lowering effects of statins, ezetimibe plus statins is a novel therapeutic strategy for the treatment of dyslipidemia in high-risk patients. Statins have been shown to ameliorate renal function and reduce proteinuria in patients with chronic kidney disease (CKD). However, effects of co-administration of ezetimibe with statins on renal damage and dysfunction in CKD patients remain unknown. In this study, we examined whether co-administration of ezetimibe with pitavastatin could augment renoprotective properties of pitavastatin in non-diabetic CKD patients with dyslipidemia. Total cholesterol, LDL-cholesterol and triglycerides levels were reduced more by co-administration of ezetimibe (10mg/day) with pitavastatin (2mg/day) (n=10) than by pitavastatin alone (n=10). In addition, ezetimibe plus pitavastatin treatment produced significant incremental reduction in proteinuria related to pitavastatin therapy alone. In univariate analyses, proteinuria was correlated with plasma levels of total cholesterol, LDL-cholesterol, triglycerides, HDL-cholesterol (inversely), asymmetric dimethylarginine, an endogenous nitric oxide synthase inhibitor, and urinary excretion levels of L-fatty acid binding protein (L-FABP), a marker of tubular injury and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker. Multiple stepwise regression analysis revealed that LDL-cholesterol (p<0.001) and urinary excretion levels of L-FABP (p=0.001) and 8-OHdG (p<0.001) were independently related to proteinuria (R(2)=0.969). Our present study demonstrated for the first time that co-administration of ezetimibe enhanced proteinuria-lowering effects of pitavastatin in non-diabetic CKD patients partly via a cholesterol-independent manner. Ezetimibe may have pleiotropic actions that could contribute to renoprotective properties of this lipid-lowering agent.
2.
Rapid stabilization of vulnerable carotid plaque within 1 month of pitavastatin treatment in patients with acute coronary syndrome.
Nakamura, T, Obata, JE, Kitta, Y, Takano, H, Kobayashi, T, Fujioka, D, Saito, Y, Kodama, Y, Kawabata, K, Mende, A, et al
Journal of cardiovascular pharmacology. 2008;(4):365-71
Abstract
We determined time course of stabilization of echolucent carotid plaques by statin therapy in patients with acute coronary syndrome (ACS). Treatment with 4 mg/d pitavastatin (n = 33) or placebo (n = 32) was initiated within 3 days after onset of ACS in 65 patients with echolucent carotid plaque. Vulnerable carotid plaques were assessed by measuring plaque echolucency using carotid ultrasound with integrated backscatter (IBS) analysis before and 1 month after treatment in all patients. The calibrated IBS value (intima-media IBS value minus adventia IBS) of vulnerable carotid plaques favorably changed at 1 month after treatment in both groups, but the echolucency at 1 month improved more in the pitavastatin than in the placebo group (pitavastatin group: -18.7 +/- 3.3 dB at pretreatment versus -12.7 +/- 2.3 dB at 1 month *P < 0.001; placebo: -19.0 +/- 3.5 dB versus -16.9 +/- 3.2 dB, P < 0.05, *P < 0.01 versus the value at 1 month in placebo group). Levels of CRP, VEGF, and TNFalpha at 1 month were significantly lower in pitavastatin than placebo group. In conclusion, pitavastatin improved carotid plaque echolucency within 1 month of therapy in patients with ACS, in association with decrease in the inflammatory biomarkers related to vulnerable plaques.
3.
Effect of pitavastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease.
Nakamura, T, Sugaya, T, Kawagoe, Y, Suzuki, T, Inoue, T, Node, K
American journal of nephrology. 2006;(1):82-6
Abstract
BACKGROUND/AIM: Urinary liver-type fatty-acid-binding protein (L-FABP) is a useful clinical marker in the monitoring of chronic kidney disease (CKD) associated with tubulointerstitial damage. Statins have been shown to be effective in the treatment of renal disease. The aim of the present study was to determine whether pitavastatin, a newly developed statin, modulates the urinary L-FABP levels in normolipidemic patients with CKD. METHODS Thirty normolipidemic mild CKD patients (18 males and 12 females, mean age 40 years, mean serum creatinine level 1.0 mg/dl) were randomly assigned to two groups: (1) pitavastatin (1 mg/day, n = 15) and (2) placebo (n = 15). Urinary protein and urinary L-FABP levels were measured before the initiation of treatment and 3 and 6 months thereafter. Twenty age-matched healthy subjects were also studied as controls. RESULTS Before treatment, the urinary L-FABP levels in 30 CKD patients (84.0 +/- 68.5 microg/g creatinine) were significantly higher than those of healthy subjects (6.4 +/- 4.2 mug/g creatinine; p < 0.001). Pitavastatin slightly reduced serum total cholesterol and triglyceride levels, but this was not statistically significant. However, pitavastatin reduced the urinary protein excretion from 1.8 to 1.0 g/day (p < 0.01), while the urinary L-FABP levels fell from 88.5 +/- 70.5 to 28.0 +/- 16.5 mug/g creatinine (p < 0.01). CONCLUSION The present data suggest that pitavastatin ameliorates tubulointerstitial damage in CKD patients independent of the lipid-lowering effect.