Theodorakopoulou Marieta P, Alexandrou Maria-Eleni, Boutou Afroditi K, Ferro Charles J, Ortiz Alberto, Sarafidis Pantelis
Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Greece.
Department of Respiratory Medicine, G. Papanikolaou Hospital, Thessaloniki, Greece.
Clin Kidney J. 2021 Dec 14;15(3):397-406. doi: 10.1093/ckj/sfab272. eCollection 2022 Mar.
Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin-angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.
高血压和慢性肾脏病（CKD）是与2019冠状病毒病（COVID-19）严重程度和死亡风险相关的最常见合并症。肾素-血管紧张素系统（RAS）阻滞剂是治疗高血压和蛋白尿性CKD的基石。在COVID-19大流行的最初几个月，出现了一种假说，即使用RAS阻滞剂可能会增加这些人群感染COVID-19的易感性和疾病严重程度。这一假说基于以下事实：血管紧张素转换酶2（ACE2）是RAS的一种反调节成分，它作为严重急性呼吸综合征冠状病毒2进入细胞的受体。初步动物研究的推断引发了这样的猜测，即RAS阻滞剂上调ACE2可能会增加与COVID-19相关不良后果的风险。然而，这些假说并未得到人类观察性和随机临床试验新出现证据的支持，表明不存在这种关联。在此，我们描述了ACE2作为RAS一部分的生理作用，讨论了其在COVID-19感染中的核心作用，并展示了来自人类研究的关于RAS阻断与COVID-19感染或相关结局之间关联的原始和最新证据，特别关注高血压和CKD。
