Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: Addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker
Effect of renin-angiotensin-aldosterone system triple blockade on non-diabetic renal disease: Addition of an aldosterone blocker, spironolactone, to combination treatment with an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker
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DOI：
10.1291/hypres.31.59
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发表时间：
2008-01-01
影响因子：
5.4
通讯作者：
Shoji, Tatsuya
中科院分区：
文献类型：
--
作者：
Furumatsu, Yoshiyuki;Nagasawa, Yasuyuki;Shoji, Tatsuya
尽管血管紧张素转换酶抑制剂（ACE-I）和血管紧张素II受体阻滞剂（ARB）联合应用双重阻断肾素-血管紧张素-醛固酮系统（RAAS）通常已被公认为肾病的治疗方法，但这种治疗在某些患者中并不完全有效。基于最近的证据表明醛固酮与肾脏疾病进展有关，本研究旨在通过在对双重阻滞反应不充分的患者中添加醛固酮阻滞剂来检查具有三种不同机制的阻滞的疗效。进行了一项为期1年的随机、开放标签、多中心、前瞻性对照研究，其中32例非糖尿病肾病患者在ACE-I（5 mg依那普利）和ARB（50 mg氯沙坦）联合治疗12周以上后，蛋白尿超过0.5 g/d。将这些患者分为两组，每组16例：三联阻断组，在ACE-I和ARB联合治疗中加入每日25 mg螺内酯;对照组，根据肌酐水平，在联合治疗中加入1 mg三氯噻嗪或20 mg呋塞米代替螺内酯。治疗1年后，三重阻断组尿蛋白水平下降58%（p < 0.05），而对照组无变化。此外，尿IV型胶原蛋白水平在三重阻断下降低了40%（p < 0.05），但在对照中没有变化。尿蛋白和尿IV型胶原的减少并不伴随着血压的降低。两种治疗的平均血清肌酐、钾和血压均无显著变化。总之，RAAS的三重阻断对于治疗非糖尿病肾病患者的蛋白尿是有效的，这些患者的尿蛋白增加对双重阻断没有足够的反应。
Although dual blockade of the renin-angiotensin-aldosterone system (RAAS) with the combination of an angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin II receptor blocker (ARB) is generally well-established as a treatment for nephropathy, this treatment is not fully effective in some patients. Based on the recent evidence implicating aldosterone in renal disease progression, this study was conducted to examine the efficacy of blockade with three different mechanisms by adding an aldosterone blocker in patients who do not respond adequately to the dual blockade. A 1-year randomized, open-label, multicenter, prospective controlled study was conducted, in which 32 non-diabetic nephropathy patients with proteinuria exceeding 0.5 g/day were enrolled after more than 12 weeks of ACE-I (5 mg enalapril) and ARB (50 mg losartan) combination treatment. These patients were allocated into two groups of 16 patients each: a triple blockade group in which 25 mg of spironolactone daily was added to the ACE-I and ARB combination treatment, and a control group in which 1 mg of trichlormethiazide or 20 mg of furosemide was added to the combination treatment instead of spironolactone depending upon the creatinine level. After 1 year of treatment, the urinary protein level decreased by 58% (p < 0.05) with the triple blockade but was unchanged in the controls. Furthermore, urinary type IV collagen level decreased by 40% (p < 0.05) with the triple blockade but was unchanged in the controls. The decreases in urinary protein and urinary type IV collagen were not accompanied by a decrease in blood pressure. Mean serum creatinine, potassium and blood pressure did not change significantly by either treatment. In conclusion, triple blockade of the RAAS was effective for the treatment of proteinuria in patients with non-diabetic nephropathy whose increased urinary protein had not responded sufficiently to a dual blockade.