ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO0011

ACE2 and TMPRSS2 Co-Localization in Proximal Tubules from Human Kidneys Obtained at Autopsy from COVID-19 Patients

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Ellis, Carla L., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Hassler, Luise, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Baig, Athar, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Studies at the single cell level have revealed that the localization of TMPRSS2 is in the distal nephron whereas ACE2 is in the proximal tubule. Since TMPRSS2 is a serine protease necessary for activation of the SARS-CoV-2 S spike protein after it binds to ACE2, this spatial separation would make it difficult to explain how SARS-CoV-2 can infect the kidney. The purpose of this study was to examine the localization of these proteins by immunofluorescence in the kidneys of patients who died from COVID-19.

Methods

Human kidney slides from a Northwestern COVID-19 repository were used after IRB approval. Slides from paraffin-embedded blocks were probed with different antibodies (ACE2, TMPRSS2, ACE, NBC-1, Aquaporin 2) for immunofluorescence studies. Mouse kidneys were also examined as additional controls.

Results

In mouse kidneys, TMPRSS2 was found in the brush border of proximal tubules and co-localized strongly with ACE2. Similarly, in human kidneys from patients who died from COVID-19, with or without AKI and from non-COVID-19 subjects, ACE2 and TMPRSS2 co-localized in the proximal tubule. TMPRSS2 and ACE2 also co-localized with ACE, a marker of the apical proximal tubule and to a lesser extent with NBC-1, a marker of the basolateral proximal tubule membrane. By contrast, TMPRSS2 and ACE2 did not co-localize with Aquaporin 2, a marker of principal cells in the collecting tubule.

Conclusion

In both mouse and human kidneys, ACE2 and TMPRSS2 co-localize in the proximal tubule. In kidneys from patients with COVID-19 with or without AKI obtained at autopsy, both proteins co-localized in the proximal tubule but not in the collecting tubule. Contrary to what was suggested from single-cell mRNA analysis, the co-localization of both proteins in the proximal tubule would make it possible for the SARS-CoV-2-ACE2 complex to be activated when coronavirus reaches the kidney.