ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

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

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /

Please note that you are viewing an archived section from 2020 and some content may be unavailable. To unlock all content for 2020, please visit the archives.

Abstract: SA-OR04

SARS-CoV-2 Receptor Networks in Diabetic Kidney Disease, BK Virus Nephropathy, and COVID-19 Associated AKI

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Menon, Rajasree, University of Michigan, Ann Arbor, Michigan, United States
  • Otto, Edgar A., University of Michigan, Ann Arbor, Michigan, United States
  • Sealfon, Rachel S., Flatiron Institute, New York, New York, United States
  • Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States
  • Wong, Aaron, Flatiron Institute, New York, New York, United States
  • Theesfeld, Chandra L., Princeton University, Princeton, New Jersey, United States
  • Chen, Xi, Flatiron Institute, New York, New York, United States
  • Wang, Yuan, Princeton University, Princeton, New Jersey, United States
  • Schaub, Jennifer A., University of Michigan, Ann Arbor, Michigan, United States
  • Berthier, Celine C., University of Michigan, Ann Arbor, Michigan, United States
  • Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States
  • Lienczewski, Chrysta C., University of Michigan, Ann Arbor, Michigan, United States
  • Godfrey, Brad A., University of Michigan, Ann Arbor, Michigan, United States
  • Sohaney, Ryann, University of Michigan, Ann Arbor, Michigan, United States
  • Looker, Helen C., National Institutes of Health, Bethesda, Maryland, United States
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
  • Naik, Abhijit S., University of Michigan, Ann Arbor, Michigan, United States
  • Nelson, Robert G., National Institutes of Health, Bethesda, Maryland, United States
  • Troyanskaya, Olga, Princeton University, Princeton, New Jersey, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
Background

COVID-19 shows increased disease burden in patients with diabetic kidney disease (DKD). SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for host cell entry, so ACE2 levels may influence SARS-CoV-2 susceptibility. We investigated how pre-existing conditions and drug treatments alter receptor expression in kidney cells (Figure 1).

Methods

Single cell RNA profiling of 7 healthy living donor kidneys, 44 DKD, 3 BK virus nephropathy (BKVN) and a urine COVID19 patient with acute kidney injury (COV-AKI) revealed ACE2 expression primarily in proximal tubular epithelial cells (PTEC).

Results

ACE2 mRNA expression levels were higher in proximal tubule epithelial cells (PTEC) in DKD versus LD, but unaltered by exposures to renin angiotensin aldosterone system inhibitors. Bayesian integrative analysis of public -omics datasets identified molecular network modules induced in ACE2 positive versus negative PTEC in DKD and BKVN (hb.flatironinstitute.org/covid-kidney), that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. Similar programs were seen in COV-AKI ACE2-positive PTEC, and overlapped with programs in SARS-CoV-2 infected cells.

Conclusion

A consistent ACE2-coregulated expression program in PTEC may interact with SARS-CoV-2 infection processes. These networks can seed further research into developing therapeutic strategies and assessing risk in patients with COVID-19.

Figure 1: Study overview. Identifying SARS-CoV-2 receptor networks in DKD, BKVN and COV-AKI using scRNAseq and integrative network analyses

Funding

  • NIDDK Support