Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Curr Opin Nephrol Hypertens. 2010 Mar;19(2):140-52. doi: 10.1097/MNH.0b013e3283361887.
Renin-angiotensin-aldosterone system (RAAS) blockade improves outcome in cardiovascular disease (CVD) and chronic kidney disease (CKD), but the residual risk during monotherapy RAAS blockade remains very high. This review discusses the place of dual RAAS blockade in improving these outcomes.
The combination of angiotensin-converting enzyme inhibitor (ACEI) with angiotensin II type 1 receptor blocker (ARB) generally had a better antihypertensive and antiproteinuric effect than monotherapy in many studies, but is also associated with more adverse effects. Unfortunately, the effect on hard renal and cardiovascular endpoints is not unequivocal. The combination of ACEI (or ARB) with aldosterone blockade has long-term benefits in heart failure, and an added effect on proteinuria in CKD, but data on hard renal endpoints are lacking. Dual blockade including renin inhibition has added antiproteinuric effects, but studies to gather long-term data are still under way. Available strategies to optimize the effect of monotherapy RAAS blockade include dose titration and correction of volume excess. Whether dual blockade has better efficacy and/or fewer adverse effects than optimized monotherapy has not been investigated.
Several options are available to increase the effect of monotherapy RAAS blockade. For proteinuric CKD, these can be combined in a stepwise approach aimed at maximal proteinuria reduction; this includes dual blockade for patients with persistent proteinuria during optimized monotherapy RAAS blockade. Long-term randomized studies, however, are needed to support the benefits of dual blockade for long-term renal and cardiovascular outcome in CKD.
肾素-血管紧张素-醛固酮系统（RAAS）阻断在心血管疾病（CVD）和慢性肾脏病（CKD）中改善预后，但单药 RAAS 阻断的残余风险仍然很高。本综述讨论了双重 RAAS 阻断在改善这些结局中的作用。
在许多研究中，血管紧张素转换酶抑制剂（ACEI）与血管紧张素 II 型 1 型受体阻滞剂（ARB）联合治疗的降压和降蛋白尿效果一般优于单药治疗，但也与更多的不良反应相关。不幸的是，对肾脏和心血管终点的影响并不明确。ACEI（或 ARB）与醛固酮阻断联合治疗心力衰竭具有长期益处，对 CKD 的蛋白尿也有额外的作用，但缺乏关于肾脏终点的硬数据。包括肾素抑制在内的双重阻断具有额外的降蛋白尿作用，但仍在进行收集长期数据的研究。优化单药 RAAS 阻断效果的几种策略包括剂量滴定和纠正容量过剩。双重阻断是否比优化的单药治疗具有更好的疗效和/或更少的不良反应尚未得到研究。
有几种选择可以增强单药 RAAS 阻断的效果。对于蛋白尿性 CKD，可以采用旨在最大程度降低蛋白尿的逐步联合治疗策略；对于优化单药 RAAS 阻断治疗后持续存在蛋白尿的患者，可以采用双重阻断。然而，需要进行长期随机研究来支持双重阻断在 CKD 中对长期肾脏和心血管结局的益处。
