Takazakura Akiko, Sakurai Masaru, Bando Yukihiro, Misu Hirofumi, Takeshita Yumie, Kita Yuki, Shimizu Akiko, Hayakawa Tetsuo, Kato Ken-Ichiro, Kaneko Shuichi, Takamura Toshinari
Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Sciences Kanazawa, Japan.
Department of Epidemiology and Public Health, Kanazawa Medical University Uchinada, Ishikawa, Japan.
J Diabetes Investig. 2015 May;6(3):346-53. doi: 10.1111/jdi.12296. Epub 2014 Nov 27.
Several studies have shown that statins suppress the progression of diabetic nephropathy. However, few reports have directly compared the renoprotective effects between potent and conventional statins.
Patients with diabetic nephropathy, selected as those with a serum creatinine level of 0.9-1.5 mg/dL and simultaneously having either microalbuminuria or positive proteinuria, were randomly assigned to one of three groups: a conventional diet therapy group, a group given 10 mg of pravastatin and a group given 10 mg of atorvastatin. Renal function was evaluated before and after a 12-month period of therapy.
The atorvastatin group had a significant decrease in low-density lipoprotein cholesterol at 3 months and thereafter compared with the other groups. The urinary albumin-to-creatinine ratio significantly decreased in the atorvastatin group; the degree of this decrease was significantly greater than that in the diet therapy group. The kidney function estimated with cystatin C (CysC) and the estimated glomerular filtration rate calculated from CysC were significantly preserved in the atorvastatin group compared with the pravastatin group. In a multivariate regression analysis, the use of atorvastatin was the only explanatory variable for the changes in CysC; this was independent of changes in low-density lipoprotein cholesterol.
Atorvastatin is more effective than pravastatin for the prevention of increase in CysC, and this renoprotective effect was considered to a result of the pleiotropic effect of atorvastatin independent of its lipid-lowering effect. This study was registered with UMIN (no. UMIN 000001774).
多项研究表明，他汀类药物可抑制糖尿病肾病的进展。然而，很少有报告直接比较强效他汀类药物和传统他汀类药物之间的肾脏保护作用。
选择血清肌酐水平为0.9 - 1.5mg/dL且同时伴有微量白蛋白尿或蛋白尿阳性的糖尿病肾病患者，随机分为三组：传统饮食治疗组、给予10mg普伐他汀的组和给予10mg阿托伐他汀的组。在治疗12个月前后评估肾功能。
与其他组相比，阿托伐他汀组在3个月及之后低密度脂蛋白胆固醇显著降低。阿托伐他汀组尿白蛋白与肌酐比值显著降低；这种降低程度显著大于饮食治疗组。与普伐他汀组相比，阿托伐他汀组中用胱抑素C（CysC）评估的肾功能以及根据CysC计算的估计肾小球滤过率得到显著保留。在多变量回归分析中，使用阿托伐他汀是CysC变化的唯一解释变量；这与低密度脂蛋白胆固醇的变化无关。
阿托伐他汀在预防CysC升高方面比普伐他汀更有效，并且这种肾脏保护作用被认为是阿托伐他汀多效性作用的结果，与其降脂作用无关。本研究已在UMIN注册（编号UMIN 000001774）。
