Cargando…

Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the kidneys. Beyond serving as a crucial endogenous regulator of the renin–angiotensin system, ACE2 also possess a unique function to facilitate a...

Descripción completa

Detalles Bibliográficos
Autores principales: Vergara, Ander, Wang, Kaiming, Colombo, Daniele, Gheblawi, Mahmoud, Rasmuson, Jaslyn, Mandal, Rupasri, Del Nonno, Franca, Chiu, Brian, Scholey, James W, Soler, María José, Wishart, David S, Oudit, Gavin Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494506/
https://www.ncbi.nlm.nih.gov/pubmed/36751625
http://dx.doi.org/10.1093/ckj/sfac215
_version_ 1784793809220009984
author Vergara, Ander
Wang, Kaiming
Colombo, Daniele
Gheblawi, Mahmoud
Rasmuson, Jaslyn
Mandal, Rupasri
Del Nonno, Franca
Chiu, Brian
Scholey, James W
Soler, María José
Wishart, David S
Oudit, Gavin Y
author_facet Vergara, Ander
Wang, Kaiming
Colombo, Daniele
Gheblawi, Mahmoud
Rasmuson, Jaslyn
Mandal, Rupasri
Del Nonno, Franca
Chiu, Brian
Scholey, James W
Soler, María José
Wishart, David S
Oudit, Gavin Y
author_sort Vergara, Ander
collection PubMed
description BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the kidneys. Beyond serving as a crucial endogenous regulator of the renin–angiotensin system, ACE2 also possess a unique function to facilitate amino acid absorption. Our observational study sought to explore the relationship between urine ACE2 (uACE2) and renal outcomes in coronavirus disease 2019 (COVID-19). METHODS: In a cohort of 104 patients with COVID-19 without acute kidney injury (AKI), 43 patients with COVID-19-mediated AKI and 36 non-COVID-19 controls, we measured uACE2, urine tumour necrosis factor receptors I and II (uTNF-RI and uTNF-RII) and neutrophil gelatinase-associated lipocalin (uNGAL). We also assessed ACE2 staining in autopsy kidney samples and generated a propensity score–matched subgroup of patients to perform a targeted urine metabolomic study to describe the characteristic signature of COVID-19. RESULTS: uACE2 is increased in patients with COVID-19 and further increased in those that developed AKI. After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with a >3-fold higher risk of developing AKI [odds ratio 3.05 (95% confidence interval 1.23‒7.58), P = .017]. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in patients with COVID-19, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2. CONCLUSIONS: 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.
format Online
Article
Text
id pubmed-9494506
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-94945062022-09-27 Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury Vergara, Ander Wang, Kaiming Colombo, Daniele Gheblawi, Mahmoud Rasmuson, Jaslyn Mandal, Rupasri Del Nonno, Franca Chiu, Brian Scholey, James W Soler, María José Wishart, David S Oudit, Gavin Y Clin Kidney J Original Article BACKGROUND: Angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed in the kidneys. Beyond serving as a crucial endogenous regulator of the renin–angiotensin system, ACE2 also possess a unique function to facilitate amino acid absorption. Our observational study sought to explore the relationship between urine ACE2 (uACE2) and renal outcomes in coronavirus disease 2019 (COVID-19). METHODS: In a cohort of 104 patients with COVID-19 without acute kidney injury (AKI), 43 patients with COVID-19-mediated AKI and 36 non-COVID-19 controls, we measured uACE2, urine tumour necrosis factor receptors I and II (uTNF-RI and uTNF-RII) and neutrophil gelatinase-associated lipocalin (uNGAL). We also assessed ACE2 staining in autopsy kidney samples and generated a propensity score–matched subgroup of patients to perform a targeted urine metabolomic study to describe the characteristic signature of COVID-19. RESULTS: uACE2 is increased in patients with COVID-19 and further increased in those that developed AKI. After adjusting uACE2 levels for age, sex and previous comorbidities, increased uACE2 was independently associated with a >3-fold higher risk of developing AKI [odds ratio 3.05 (95% confidence interval 1.23‒7.58), P = .017]. Increased uACE2 corresponded to a tubular loss of ACE2 in kidney sections and strongly correlated with uTNF-RI and uTNF-RII. Urine quantitative metabolome analysis revealed an increased excretion of essential amino acids in patients with COVID-19, including leucine, isoleucine, tryptophan and phenylalanine. Additionally, a strong correlation was observed between urine amino acids and uACE2. CONCLUSIONS: 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. Oxford University Press 2022-09-21 /pmc/articles/PMC9494506/ /pubmed/36751625 http://dx.doi.org/10.1093/ckj/sfac215 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Article
Vergara, Ander
Wang, Kaiming
Colombo, Daniele
Gheblawi, Mahmoud
Rasmuson, Jaslyn
Mandal, Rupasri
Del Nonno, Franca
Chiu, Brian
Scholey, James W
Soler, María José
Wishart, David S
Oudit, Gavin Y
Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury
title Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury
title_full Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury
title_fullStr Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury
title_full_unstemmed Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury
title_short Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury
title_sort urinary angiotensin-converting enzyme 2 and metabolomics in covid-19-mediated kidney injury
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9494506/
https://www.ncbi.nlm.nih.gov/pubmed/36751625
http://dx.doi.org/10.1093/ckj/sfac215
work_keys_str_mv AT vergaraander urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT wangkaiming urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT colombodaniele urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT gheblawimahmoud urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT rasmusonjaslyn urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT mandalrupasri urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT delnonnofranca urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT chiubrian urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT scholeyjamesw urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT solermariajose urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT wishartdavids urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury
AT ouditgaviny urinaryangiotensinconvertingenzyme2andmetabolomicsincovid19mediatedkidneyinjury