Kidney Week

Abstract: FR-PO024

Angiotensin-Converting Enzyme 2 and Urine Amino Acid Excretion Increase in COVID-19 Patients With AKI

Session Information

• COVID-19: AKI Outcomes, Biomarkers, Treatments, Case Reports
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Coronavirus (COVID-19)

• 000 Coronavirus (COVID-19)

Authors

• Vergara, Ander, University of Alberta, Edmonton, Alberta, Canada

Ander Vergara,

• Wang, Kaiming, University of Alberta, Edmonton, Alberta, Canada

Kaiming Wang,

• Colombo, Daniele, INMI Lazzaro Spallanzani IRCCS, Roma, Lazio, Italy

Daniele Colombo,

• Gheblawi, Mahmoud, University of Alberta, Edmonton, Alberta, Canada

Mahmoud Gheblawi,

• Rasmuson, Jaslyn C., University of Alberta, Edmonton, Alberta, Canada

Jaslyn C. Rasmuson,

• Mandal, Rupasri, University of Alberta, Edmonton, Alberta, Canada

Rupasri Mandal,

• Del Nonno, Franca, INMI Lazzaro Spallanzani IRCCS, Roma, Lazio, Italy

Franca Del Nonno,

• Chiu, Brian, University of Alberta, Edmonton, Alberta, Canada

Brian Chiu,

• Scholey, James W., University Health Network, Toronto, Ontario, Canada

James W. Scholey,

• Soler, Maria Jose, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain

Maria Jose Soler,

• Wishart, David S., University of Alberta, Edmonton, Alberta, Canada

David S. Wishart,

• Oudit, Gavin, University of Alberta, Edmonton, Alberta, Canada

Gavin Oudit,

Background

Angiotensin-converting enzyme 2(ACE2), the receptor for SARS-CoV-2, is highly expressed in the kidneys. ACE2 also possess a unique function to facilitate amino acid absorption. A persistent elevation in plasma ACE2 during COVID-19 is related to increased mortality. The present study sought to explore the relationship between urine ACE2(uACE2) and renal outcomes in COVID-19 patients.

Methods

In 104 COVID-19 patients without acute kidney injury(AKI), 43 patients with COVID-19-mediated AKI, and 36 non-COVID-19 controls, uACE2, urine tumor necrosis factor receptors I and II(uTNF-RI and uTNF-RII), neutrophil gelatinase-associated lipocalin(uNGAL), and urine albumin-creatinine ratio were measured. We also assessed ACE2 staining in autopsy kidney samples and generated a propensity-score matched subgroup to perform a targeted urine metabolomic study to describe the characteristic urine signature of COVID-19.

Results

uACE2 was increased in patients with COVID-19, and further increased in those that developed AKI(Figure 1). After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with over 3-fold higher risk(OR 3.05,95%CI:1.23-7.58, p=0.017) of developing AKI. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII, suggesting that ADAM17 could be responsible for ACE2 shedding. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in COVID-19 patients, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2(Figure 1).

Conclusion

Elevated uACE2 is related to AKI in patients with COVID-19. The loss of tubular ACE2 during SARS-CoV-2 infection demonstrates a potential link between aminoaciduria and proximal tubular injury.

Funding

• Government Support – Non-U.S.