Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients

Author(s)

Cruz, Nayara Azinheira Nobrega ^[1] ; Oliveira, Lilian Caroline Goncalves de ^[1] ; Silva Junior, Helio Tedesco ^[1] ; Pestana, Jose Osmar Medina ^[1] ; Casarini, Dulce Elena ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Med, Div Nephrol, Sao Paulo - Brazil

• Document type: Review article
• Source: FRONTIERS IN PHYSIOLOGY; v. 12, AUG 23 2021.
• Web of Science Citations: 0

Abstract

Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 in Wuhan, China. The etiological agent of this disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the high transmissibility of the virus led to its rapid global spread and a major pandemic (ongoing at the time of writing this review). The clinical manifestations of COVID-19 can vary widely from non-evident or minor symptoms to severe acute respiratory syndrome and multi-organ damage, causing death. Acute kidney injury (AKI) has been recognized as a common complication of COVID-19 and in many cases, kidney replacement therapy (KRT) is required. The presence of kidney abnormalities on hospital admission and the development of AKI are related to a more severe presentation of COVID-19 with higher mortality rate. The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), which is widely expressed in human organs and is especially abundant in the kidneys. A debate on the role of ACE2 in the infectivity and pathogenesis of COVID-19 has emerged: Does the high expression of ACE2 promotes higher infectivity and more severe clinical manifestations or does the interaction of SARS-CoV-2 with ACE2 reduce the bioavailability of the enzyme, depleting its biological activity, which is closely related to two important physiological systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), thereby further contributing to pathogenesis. In this review, we discuss the dual role of ACE2 in the infectivity and pathogenesis of COVID-19, highlighting the effects of COVID-19-induced ACE2 depletion in the renal physiology and how it may lead to kidney injury. The ACE2 downstream regulation of KKS, that usually receives less attention, is discussed. Also, a detailed discussion on how the triad of symptoms (respiratory, inflammatory, and coagulation symptoms) of COVID-19 can indirectly promote renal injury is primary aborded.</p> (AU)

• FAPESP's process: 17/17027-0 - Hormonal systems in renal and cardiovascular diseases: from cell biology to new physiological paradigms with advances for therapeutics
• Grantee: Dulce Elena Casarini
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/16653-7 - Analysis of alterations in renin-angiotensin and kallikrein-kinin systems in Pediatric Obesity and its contribution to associated complications
• Grantee: Nayara Azinheira Nobrega Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/23953-7 - Exposomic applied to the profile of metabolites and obesogenic compounds in the urine of unhealthy prepubescent
• Grantee: Lilian Caroline Gonçalves de Oliveira
• Support Opportunities: Regular Research Grants