Kato Sawako, Maruyama Shoichi, Makino Hirofumi, Wada Jun, Ogawa Daisuke, Uzu Takashi, Araki Hisazumi, Koya Daisuke, Kanasaki Keizo, Oiso Yutaka, Goto Motomitsu, Nishiyama Akira, Kobori Hiroyuki, Imai Enyu, Ando Masahiko, Matsuo Seiichi
Department of Nephrology, Nagoya University Graduate School of Medicine, Aichi, Japan.
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Clin Exp Nephrol. 2015 Dec;19(6):1098-106. doi: 10.1007/s10157-015-1106-2. Epub 2015 Mar 21.
Several studies have demonstrated that spironolactone has an anti-albuminuric property in diabetic nephropathy. As an adverse event, spironolactone often induces the elevation of creatinine levels with hypotension and hyperkalemia. Therefore, we aimed to evaluate the efficacy and safety of spironolactone in Japanese patients with type 2 diabetes treated with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
Fifty-two Japanese patients with diabetic nephropathy and albuminuria (100 mg/gCr-2000 mg/gCr) treated with renin-angiotensin system (RAS) blockade were enrolled in a prospective, randomized, open-label study. The patients were subjected to add-on treatment with spironolactone 25 mg once daily and compared with matched controls for 8 weeks. The primary outcome was a reduction in the rate of albuminuria at 8 weeks compared with the baseline value. This study was registered with UMIN Clinical Trials Registry (000008016).
Albuminuria was reduced by 33 % (95 % confidence interval: 22-54; P = 0.0002) at 8 weeks with spironolactone. In the spironolactone group, blood pressure tended to lower and the estimated glomerular filtration rate (eGFR) was significantly decreased compared to those in the control group. When adjusted by systolic blood pressure and eGFR, spironolactone treatment still showed a significant effect on albuminuria reduction in a linear mixed model (coefficient ± standard error; 514.4 ± 137.6 mg/gCr, P < 0.0005). No patient was excluded from the study because of hyperkalemia.
Spironolactone reduced albuminuria along with conventional RAS inhibitors in patients with diabetic nephropathy. Our study suggests that spironolactone exerts anti-albuminuric effects independent of systemic hemodynamic alterations.
多项研究表明，螺内酯对糖尿病肾病具有抗蛋白尿作用。作为一种不良事件，螺内酯常导致肌酐水平升高，并伴有低血压和高钾血症。因此，我们旨在评估螺内酯在接受血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂治疗的日本2型糖尿病患者中的疗效和安全性。
52例接受肾素-血管紧张素系统（RAS）阻滞剂治疗的日本糖尿病肾病和蛋白尿（100mg/gCr - 2000mg/gCr）患者纳入一项前瞻性、随机、开放标签研究。患者接受每日一次25mg螺内酯的附加治疗，并与匹配的对照组进行8周比较。主要结局是与基线值相比，8周时蛋白尿率降低。本研究已在UMIN临床试验注册中心注册（000008016）。
使用螺内酯8周时，蛋白尿减少了33%（95%置信区间：22 - 54；P = 0.0002）。在螺内酯组中，血压有降低趋势，与对照组相比，估计肾小球滤过率（eGFR）显著降低。在调整收缩压和eGFR后，螺内酯治疗在线性混合模型中对蛋白尿减少仍显示出显著效果（系数±标准误；514.4±137.6mg/gCr，P < 0.0005）。没有患者因高钾血症被排除在研究之外。
在糖尿病肾病患者中，螺内酯与传统RAS抑制剂一起可降低蛋白尿。我们的研究表明，螺内酯发挥抗蛋白尿作用独立于全身血流动力学改变。
