Mineralocorticoid receptor blockade suppresses dietary salt-induced ACEI/ARB-resistant albuminuria in non-diabetic hypertension: a sub-analysis of evaluate study
Mineralocorticoid receptor blockade suppresses dietary salt-induced ACEI/ARB-resistant albuminuria in non-diabetic hypertension: a sub-analysis of evaluate study
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DOI：
10.1038/s41440-018-0201-7
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发表时间：
2019-04-01
影响因子：
5.4
通讯作者：
Fujita, Toshiro
中科院分区：
文献类型：
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作者：
Nishimoto, Mitsuhiro;Ohtsu, Hiroshi;Fujita, Toshiro
在高血压合并慢性肾脏疾病（CKD）患者中，过量的食盐摄入可以抵消肾素-血管紧张素系统（RAS）阻断对肾脏的保护作用。在啮齿类动物中，盐负荷通过激活矿皮质激素受体（MR）而不依赖于血浆醛固酮水平，从而诱发高血压和肾损伤。因此，高盐诱导的对RAS阻断的抗性可能是由MR激活介导的。为了验证这一点，我们进行了一项事后分析，比较了依普利酮联合用药与常规降压药对尿抗蛋白尿治疗效果的影响。因此，304名接受ras阻断治疗的非糖尿病高血压患者根据盐摄入量（基线时估计24小时尿钠排泄量）被分为三组，并比较了52周时尿白蛋白与肌酐比值（UACR）相对于基线降低的百分比。在钠排泄量最高的各组中，接受依普利酮治疗的患者UACR的降低幅度明显高于安慰剂组（-22.5% vs. +21.8%, p = 0.02）。在最低分位数（-10.2% vs. -0.84%, p = 0.65）或中间分位数（-19.5% vs. +9.5%, p = 0.22）中没有观察到这种差异。观察到相似的收缩压变化。在整个队列中，UACR的降低与收缩压的降低呈正相关（r(2) = 0.04, p = 0）。2)。这些结果支持了过量盐摄入可以通过激活mr来增强对RAS阻断的抵抗力的假设，也提示依普利酮加RAS阻断可能对高血压患者的CKD有效，特别是那些盐摄入过量的患者。
Excessive dietary salt intake can counteract the renoprotective effects of renin-angiotensin system (RAS) blockade in hypertensive patients with chronic kidney disease (CKD). In rodents, salt loading induces hypertension and renal damage by activating the mineralocorticoid receptor (MR) independently of plasma aldosterone levels. Thus, high salt-induced resistance to RAS blockade may be mediated by MR activation. To test this, a post hoc analysis of the Eplerenone Combination Versus Conventional Agents to Lower Blood Pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial was conducted. Thus, 304 non-diabetic hypertensive patients on RAS-blocking therapy were divided into tertiles according to salt intake (estimated 24-h urinary sodium excretion at baseline) and compared in terms of percent reduction in urinary albumin-to-creatinine ratio (UACR) at 52 weeks relative to baseline. The eplerenone-treated patients in the highest sodium excretion tertile exhibited significantly greater reduction in UACR than the placebo subjects in the same tertile (-22.5% vs. +21.8%, p = 0.02). This disparity was not observed in the lowest (-10.2% vs. -0.84%, p = 0.65) or middle (-19.5% vs. +9.5%, p = 0.22) tertiles. Similar systolic blood pressure changes were observed. In the whole cohort, reduction in UACR correlated positively with reduction in systolic blood pressure (r(2) = 0.04, p = 0 .0 2) . These results support the hypothesis that excessive salt intake can enhance resistance to RAS blockade by activating MR. They also suggest that eplerenone plus RAS blockade may be effective for CKD in hypertensive patients, especially those with excessive salt intake.