肾素-血管紧张素-醛固酮系统与心力衰竭中的肾脏相互作用。,Journal of the Renin-Angiotensin-Aldosterone System

当前位置： X-MOL 学术 › J. Renin Angiotensin Aldosterone Syst. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

肾素-血管紧张素-醛固酮系统与心力衰竭中的肾脏相互作用。
Journal of the Renin-Angiotensin-Aldosterone System ( IF 2.1 ) Pub Date : 2019-11-18 , DOI: 10.1177/1470320319889415
João Pedro Ferreira ₁ , Patrick Rossignol ₁ , Faiez Zannad ₁

Affiliation

肾素-血管紧张素-醛固酮系统（RAAS）与心力衰竭（HF）患者的肾脏之间的相互作用可能导致高度复杂和具有挑战性的临床情况。在这些情况下，恶化的肾功能（WRF）和/或水电解质改变（尤其是高钾血症）通常会提高临床医生的意识，从而导致下游决策（例如，改变药物和/或其剂量），这可能会给患者带来后果。^1个尽管如此，应该指出的是，WRF（HF患者不良结局的主要决定因素）可能是多因素起源的，而RAAS抑制剂（RAASi）是其多种原因之一。认为发生这种情况是因为HF中的RAAS激活导致肾小球传出的小动脉血管收缩，从而保留了肾小球滤过（面对由HF引起的肾小球灌注压力下降）。通过减少这种神经激素的激活，RAAS阻滞剂可以降低肾小球的灌注压力（降低全身动脉和肾小球的传入小动脉压，同时还可以防止代偿性传入小动脉收缩）并引起WRF。²但是，长期使用RAASi治疗可能会减轻肾功能恶化，这表明肌酐最初的升高在某些人群中可能与临床无关。³在神经激素拮抗剂充血或滴定时，血清肌酐/ WRF的增加也很常见，这主要是由于loop利尿剂和/或RAASi对肾脏血液动力学的影响。最近的数据显示，当使用HF药物（即血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂，盐皮质激素受体拮抗剂（MRA），β受体阻滞剂和利尿剂）持续48小时时，血清肌酐降低，但利钠肽和心脏容量增加。⁴这些数据支持血清肌酐升高的概念，不应单独评估WRF，而应在整个临床情况下加以考虑：并非血清肌酐的所有升高都会对预后产生不利影响。例如，一项荟萃分析显示，随机分配到RAASi治疗的射血分数降低（HFrEF）的HF患者的WRF与安慰剂组的WRF相比死亡率较低。⁵应当强调的是，RAASi具有令人信服的证据，可以延长HFrEF患者的生存期并降低其发病率，美国和欧洲指南均将其推荐为I级证据级别A。相比之下，无论是否使用RAASi，射血分数保持不变（HFpEF）的HF患者的WRF均与增加的事件相关。这是因为迄今为止，HFpEF试验未能显示出明显的发病率和死亡率改善。⁵尽管如此，在TOPCAT（保留射血分数的心力衰竭中的螺内酯）试验中，螺内酯应特别注意。⁶在TOPCAT中，只有来自美洲的患者才具有与HFpEF兼容的特征以及足够的血液中药物代谢物水平。^7,8因此，在考虑这一HFpEF人群时，螺内酯可改善结局，而与基线估计的肾小球滤过率无关。但是，在肾功能受损的患者中观察到更多的不良事件，包括WRF，因此建议进行密切的实验室监测。⁹根据最新的美国心脏协会/美国心脏病学会/美国心力衰竭学会（AHA / ACC / HFSA）指南，螺内酯对HFpEF的适应症为IIb级。¹⁰

"点击查看英文标题和摘要"

Renin-angiotensin-aldosterone system and kidney interactions in heart failure.

The interplay between the renin-angiotensin-aldosterone system (RAAS) and kidneys in patients with heart failure (HF) can lead to highly complex and challenging clinical scenarios. Among these scenarios, worsening renal function (WRF) and/or hydro-electrolytic alterations (hyperkalemia in particular) often raise clinicians’ awareness leading to downstream decisions (e.g. change in medications and/or its dosages), which can have consequences for the patients.¹ It should, nonetheless, be noted that WRF (a major determinant of adverse outcomes in HF patients) may be of multifactorial origin and the RAAS inhibitors (RAASi) are one of its multiple causes. This is thought to occur because RAAS activation in HF leads to glomerular efferent arteriolar vasoconstriction that preserves glomerular filtration (in the face of a fall in glomerular perfusion pressure caused by HF). By reducing this neurohormonal activation, RAAS blockers can reduce the glomerular perfusion pressure (reducing systemic arterial and glomerular afferent arteriolar pressure while also preventing the compensatory efferent arteriolar constriction) and cause WRF.² However, used chronically, RAASi treatment may attenuate renal function deterioration, suggesting an initial creatinine rise may not be clinically relevant in certain populations.³ Increment in serum creatinine/WRF occurring in the setting of decongestion or titration of neurohormonal antagonists is also commonly encountered, primarily as a result of the effects of loop diuretics and/or of RAASi on renal hemodynamics. Recent data showed that when HF medications (i.e. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists (MRAs), β-blockers and diuretics) were held for 48 hours, serum creatinine decreased but natriuretic peptides and cardiac volumes increased.⁴ These data support the concept that serum creatinine increases and WRF should not be evaluated in isolation but rather considered in the context of the whole clinical scenario: not all increases in serum creatinine adversely affect prognosis. For example, a meta-analysis showed that WRF in patients with HF with reduced ejection fraction (HFrEF) randomized to an RAASi therapy was associated with lower mortality than WRF on placebo.⁵ It should be emphasized that RAASi have convincing evidence of benefit on prolonging survival and reducing morbidity in patients with HFrEF, and both United States and European guidelines give a Class I, Level of Evidence A recommendation for their use. In contrast, WRF in patients with HF with preserved ejection fraction (HFpEF) was associated in increased events regardless of the use of RAASi. This is because, to date, the HFpEF trials failed to demonstrate a clear morbidity and mortality improvement.⁵ Despite this, a particularity should be noted with spironolactone in the TOPCAT (Spironolactone for Heart Failure with Preserved Ejection Fraction) trial.⁶ In TOPCAT only patients from the Americas had characteristics compatible with HFpEF and adequate blood levels of the drug metabolites.^7,8 Hence, when considering this HFpEF population, spironolactone improved outcomes regardless of the baseline estimated glomerular filtration rate; however, more adverse events, including WRF, were observed in patients with impaired renal function in whom close laboratory monitoring is recommended.⁹ In concordance, the updated American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) guidelines give spironolactone a class IIb indication for HFpEF.¹⁰

更新日期：2019-11-18

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南