In our Perspective article, we aimed to discuss the emerging mechanisms that might be involved in the pathophysiology of coronavirus disease 2019 (COVID-19)–associated AKI and emphasized the need for more information. At the time of writing, data were largely limited to the two studies from China reporting data from autopsies. We refrained from speculating about therapies because we felt that it would be premature and speculative.
We are not aware that angiotensin-receptor blockers could compete with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for angiotensin-converting enzyme 2 (ACE2) and block the binding of the virus. In fact, these agents do not bind to ACE2 and therefore any connection would have to be indirect.1,2 Some studies have shown upregulation of ACE2 by angiotensin-receptor blockers.3 The significance of this finding remains unclear regarding infectivity by SARS-CoV-2 and the course of COVID-19 and its manifestations, including AKI.1,2 Concerning the potential use of renin-angiotensin system (RAS) blockers to protect the kidneys in patients with COVID-19, we see pros and cons as is the case in other forms of AKI.4 Angiotensin II is upregulated in AKI in general and this may be exacerbated in COVID-19–associated AKI if ACE2 is suppressed as has been hypothesized. In this regard, the use of RAS blockers could be beneficial but one needs to be mindful of their hypotensive action that may limit their use. A shorter variant of ACE2 that is filterable by the glomerular filtration barrier has been shown to prevent/attenuate AKI in the ischemia-reperfusion model in mice (M. Shirazi, Y, Wysocki, M. Ye, C. Haney, M. Zhao, Y.S. Kanwar, et al.: A novel ACE2 truncate for acute kidney injury, 2019).5 This could be a better approach, in our opinion, than the use of RAS blockade in the setting of AKI, but this is speculative owing to the lack of human studies. In addition, soluble ACE2 could bind SARS-CoV-2, acting as a decoy so that viral uptake by the membrane-bound full-length ACE2 would be greatly diminished, thereby potentially providing a much-needed therapy for COVID-19.6
Disclosures
D. Batlle is a coinventor of a patent Active Low Molecular Weight Variants of Angiotensin Converting Enzyme 2, and founder of Angiotensin Therapeutics Inc. All remaining authors have nothing to disclose.
Funding
D. Batlle was funded by National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK104785.
Acknowledgments
Dr. Maria Jose Soler reports personal fees from NovoNordisk, personal fees from Janssen, non-financial support from Boehringer, non-financial support from Eli Lilly, personal fees from AstraZeneca, personal fees and non-financial support from Esteve, personal fees from FMC, and personal fees from Mundipharma, outside the submitted work.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
See related letters to the editor, “Possible Protective Effect of Renin-Angiotensin System Inhibitors in COVID-19 Induced Acute Kidney Injury,” on pages 1917–1917.
References
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