ACE2, the kidney and the emergence of COVID-19 two decades after ACE2 discovery

Clin Sci (Lond). 2020 Nov 13;134(21):2791-2805. doi: 10.1042/CS20200484.

Abstract

Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1-7. With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease. We also describe the emerging kidney manifestations of COVID-19, namely the frequent development of acute kidney injury. The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.

Keywords: COVID-19; SARS-CoV-2; angiotensin converting enzyme 2; renin-angiotensin system.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Kidney Injury / enzymology
  • Acute Kidney Injury / virology
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Antiviral Agents / therapeutic use
  • Betacoronavirus / drug effects
  • Betacoronavirus / pathogenicity*
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / enzymology*
  • Coronavirus Infections / virology
  • Diabetes Mellitus / enzymology
  • Diabetes Mellitus / physiopathology
  • History, 21st Century
  • Host-Pathogen Interactions
  • Humans
  • Hypertension / enzymology
  • Hypertension / physiopathology
  • Kidney / enzymology*
  • Kidney / physiopathology
  • Kidney Diseases / drug therapy
  • Kidney Diseases / enzymology*
  • Kidney Diseases / physiopathology
  • Pandemics
  • Peptidyl-Dipeptidase A / history
  • Peptidyl-Dipeptidase A / metabolism*
  • Peptidyl-Dipeptidase A / therapeutic use
  • Pneumonia, Viral / enzymology*
  • Pneumonia, Viral / virology
  • Receptors, Virus / history
  • Receptors, Virus / metabolism*
  • SARS-CoV-2

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antiviral Agents
  • Receptors, Virus
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2