Feng Yan-Huan, Fu Ping
Department of Internal Medicine, Division of Nephrology; West China Biostatistics and Cost-benefit Analysis Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Chin Med J (Engl). 2016 Jan 5;129(1):81-7. doi: 10.4103/0366-6999.172599.
To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system (RAAS) among patients with type 2 diabetic kidney disease.
We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use of monotherapy, without applying any language restrictions. Keywords for the searches included "diabetic nephropathy," "chronic kidney disease," "chronic renal insufficiency," "diabetes mellitus," "dual therapy," "combined therapy," "dual blockade," "renin-angiotensin system," "angiotensin-converting enzyme inhibitor," "angiotensin-receptor blocker," "aldosterone blockade," "selective aldosterone blockade," "renin inhibitor," "direct renin inhibitor," "mineralocorticoid receptor blocker," etc.
The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus.
Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin II receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons.
Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an evidence-based practice.
探讨肾素-血管紧张素-醛固酮系统（RAAS）双重阻断疗法在2型糖尿病肾病患者中的疗效与安全性。
我们检索了主要文献库，包括Cochrane对照试验中心注册库、MEDLINE和EMBASE，以查找1990年1月至2015年10月发表的随机临床试验，这些试验比较了RAAS双重阻断疗法与单一疗法的疗效和安全性，且未设语言限制。检索关键词包括“糖尿病肾病”“慢性肾病”“慢性肾功能不全”“糖尿病”“双重治疗”“联合治疗”“双重阻断”“肾素-血管紧张素系统”“血管紧张素转换酶抑制剂”“血管紧张素受体阻滞剂”“醛固酮阻断”“选择性醛固酮阻断”“肾素抑制剂”“直接肾素抑制剂”“盐皮质激素受体阻滞剂”等。
对入选的文章进行了仔细审查。我们排除了患者肾脏损害与糖尿病以外疾病相关的随机临床试验。
血管紧张素转换酶抑制剂联合血管紧张素II受体阻滞剂的联合治疗有望更全面地阻断RAAS并更好地控制高血压。然而，现有文献结果不一，尤其是在患者安全性方面。鉴于此，我们进行了全面的文献综述，以解释RAAS双重阻断的理论依据，并讨论其利弊。
尽管最近一些大规模研究结果为阴性，但鉴于RAAS功能和作用的复杂性，宣称双重阻断失败可能为时过早。有必要进行进一步试验，以研究这种联合治疗作为一种循证实践的效果。
