Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure.
Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure.
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DOI：
10.1016/j.xkme.2022.100465
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发表时间：
2022-06
期刊：
影响因子：
3.9
通讯作者：
Testani, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Amatruda, Jonathan G.;Scherzer, Rebecca;Rao, Veena S.;Ivey-Miranda, Juan B.;Shlipak, Michael G.;Estrella, Michelle M.;Testani, Jeffrey M.
心力衰竭的治疗依赖于袢利尿剂来诱导钠尿和缓解充血，但该治疗通常受到利尿剂抵抗的限制。我们探讨了肾素-血管紧张素-醛固酮系统（RAAS）激活与利尿反应的关系。观察性队列。在监测环境中，给予容量正常的慢性心力衰竭非卧床成人托拉塞米。血浆总肾素、活性肾素、血管紧张素原和醛固酮水平。尿总肾素和血管紧张素原水平。利尿剂量加倍时的钠排出量和利尿剂量加倍时的钠排泄分数。稳健的线性回归模型估计每个RAAS中间结果的关联。该分析包括56名参与者，中位年龄为65岁; 50%为女性，41%为黑人。家庭利尿剂的中位剂量为80 mg呋塞米当量。在未校正和多变量校正模型中，较高水平的RAAS指标通常与较低的利尿效率相关。较高的血浆总肾素水平与利尿剂剂量加倍时较低的钠排出量显著相关（β = −0.41 [−0.76，−0.059]/SD变化），经调整;较高的血浆总的和活性的肾素与较低的每倍利尿剂剂量的钠排泄分数显著相关（分别为β = −0.48 [−0.83，−0.14]和β = −0.51 [−0.95，−0.08]）。按RAAS抑制剂使用分层并没有实质性改变这些关联。小样本量;高度选择的参与者;关联可能不是因果关系。在RAAS激活的多种测量中，较高的血浆总和活性肾素水平始终与较低的利尿反应相关。这些发现突出了利尿剂抵抗的潜在驱动因素，并强调了通过RAAS阻断增强的降压治疗的高质量试验的必要性。
Heart failure treatment relies on loop diuretics to induce natriuresis and decongestion, but the therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response. Observational cohort. Euvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment. Plasma total renin, active renin, angiotensinogen, and aldosterone levels. Urine total renin and angiotensinogen levels. Sodium output per doubling of diuretic dose and fractional excretion of sodium per doubling of diuretic dose. Robust linear regression models estimated the associations of each RAAS intermediate with outcomes. The analysis included 56 participants, and the median age was 65 years; 50% were women, and 41% were Black. The median home diuretic dose was 80-mg furosemide equivalents. In unadjusted and multivariable-adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency. Higher plasma total renin remained significantly associated with lower sodium output per doubling of diuretic dose (β = −0.41 [−0.76, −0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower fractional excretion of sodium per doubling of diuretic dose (β = −0.48 [−0.83, −0.14] and β = −0.51 [−0.95, −0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations. Small sample size; highly selected participants; associations may not be causal. Among multiple measures of RAAS activation, higher plasma total and active renin levels were consistently associated with lower diuretic response. These findings highlight the potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.
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影响因子：
9.7
作者：
McMurray, John J. V.;Pitt, Bertram;Lewsey, Jim
通讯作者：
Lewsey, Jim
影响因子：
9.7
作者：
Kula, Alexander J.;Hanberg, Jennifer S.;Testani, Jeffrey M.
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DOI：
10.1152/ajprenal.00337.2002
发表时间：
2003-05-01
影响因子：
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作者：
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作者：
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19.6
作者：
Kobori, H;Harrison-Bernard, LM;Navar, LG
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