A recent article by Batlle et al.1 entitled “AKI in COVID-19: Emerging Evidence of a Distinct Pathophysiology” has discussed comprehensively the possible pathophysiology of AKI in novel coronavirus disease 2019 (COVID-19), a complication of COVID-19 that many have largely ignored.
Although the authors were right to avoid speculating about specific interventions until a full picture has been obtained, we feel that sound hypotheses with evidence extrapolated from the COVID-19 population may help in the design of clinical trials or even prospective studies to better understand what works and what does not, since in the field of medicine it is always about testing hypotheses (without causing harm), especially amid this COVID-19 pandemic where many lives have been claimed due to complications in such a short period of time.
It has now been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for COVID-19, gains entry into host cells through an angiotensin-converting enzyme 2 (ACE2) protein, which is also abundantly expressed in the kidney. Authors have speculated about direct viral infection of the kidney, where SARS-CoV-2 gains entry through the ACE2 protein of the proximal tubule. In this sense, the use of renin-angiotensin system (RAS) inhibitors, including ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), may be protective toward kidney injury.
Firstly, ARBs could compete with SARS-CoV-2 for ACE2-expressing proximal tubular cells, block the binding, and hence the attachment of SARS-CoV-2 to ACE2, thereby inhibiting its entry into the cells. In this way, there may be less entry, if not entirely of no entry, of SARS-CoV-2 into proximal tubular cells. Thus, the proximal tubular cells at risk may be limited, and tubular function of the kidney may be better preserved. Secondly, downregulation of ACE2 upon viral invasion and subsequent increased production of angiotensin II seems to drive the occurrence of kidney injury.2 Both ACE inhibitors and ARBs could block the physiologic effect of angiotensin II.
The protective ability of RAS inhibitors may have been hinted in a prospective cohort study of 701 patients with COVID-19. Cheng et al.3 investigated the association between in-hospital medications (on admission and during hospitalization) and the development of AKI among patients with COVID-19. It was noted that none of the patients who were taking RAS inhibitors on admission or during hospitalization for COVID-19 developed AKI. In contrast, almost all patients with COVID-19 who had AKI were receiving antibiotics (35/36; 97%), a well known causative agent for AKI.4
Disclosures
All authors have nothing to disclose.
Funding
None.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
References
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