Aldosterone in the development and progression of renal injury
Aldosterone in the development and progression of renal injury
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DOI：
10.1111/j.1523-1755.2004.00701.x
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发表时间：
2004-07-01
影响因子：
19.6
通讯作者：
Hollenberg, NK
中科院分区：
文献类型：
--
作者：
Hollenberg, NK
背景。肾素-血管紧张素-醛固酮系统（RAAS）与高血压和肾病有关。直到最近，醛固酮要么没有被考虑，要么被认为是这一过程中相对次要的组成部分——这一贡献可以通过血管紧张素转换酶（ACE）抑制或血管紧张素受体阻断来抵消。在Medline上进行了检索，以确定描述醛固酮在肾功能障碍发病机制中的作用的相关文献。越来越多的实验和临床研究证据表明，醛固酮升高是中小动脉损伤和肾病的独立因素。局部和全身来源的过量矿皮质激素受体刺激可促进靶器官功能障碍、血管损伤和纤维化，而不受RAAS其他因素的影响。通过ACE抑制或血管紧张素受体阻断RAAS通常不能获得矿化皮质激素对中小血管的最佳保护作用。近期临床研究的初步数据表明，醛固酮阻断可保护肾脏，显著降低蛋白尿，其作用超出了ACE抑制或血管紧张素受体阻断的作用，且不依赖于有益的降压作用，可保护糖尿病和高血压患者免受血管损伤。选择性醛固酮阻滞剂eplerenone的醛固酮阻断，与其他RAAS抑制剂联合，可能具有肾保护作用，应考虑作为有肾脏或心血管疾病表达风险的糖尿病和高血压患者治疗方案的一个组成部分。应该高度重视开展确定这一作用所需的随机对照试验。
Background. The renin-angiotensin-aldosterone system (RAAS) contributes to hypertension and nephropathy. Until recently, aldosterone either has not been considered or has been considered a relatively minor component of the process - a contribution that could be negated with angiotensin-converting enzyme (ACE) inhibition or angiotensin receptor blockade.Methods. A Medline search was performed to identify relevant literature describing the role of aldosterone in the pathogenesis of renal dysfunction.Results. Growing evidence from experimental and clinical studies indicates that increased aldosterone is an independent contributor to small- and medium-sized arterial injury and nephropathy. Excess mineralocorticoid receptor stimulation of local and systemic origin promotes target organ dysfunction, vascular injury, and fibrosis, independent of the effects of other elements of the RAAS. Blockade of the RAAS with ACE inhibition or angiotensin receptor blockade often does not confer optimal protection from the effects of mineralocorticoids on small- and medium-sized blood vessels. Recent preliminary data from clinical studies indicate that aldosterone blockade protects the kidneys, sharply decreases proteinuria, beyond the activities of ACE inhibition or angiotensin receptor blockade and independent of beneficial blood pressure effects, and can protect patients from vascular injury associated with diabetes mellitus and hypertension.Conclusion. Aldosterone blockade with the selective aldosterone blocker eplerenone, in combination with other RAAS inhibitors, is probably renoprotective and should be considered as a component of the treatment regimens of diabetic and hypertensive patients at risk for renal or cardiovascular disease expression. A high priority should be placed on developing the randomized, controlled trials required to establish that role.