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SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule
Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remain...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Society of Nephrology. Published by Elsevier Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416689/ https://www.ncbi.nlm.nih.gov/pubmed/32791255 http://dx.doi.org/10.1016/j.kint.2020.07.019 |
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author | Werion, Alexis Belkhir, Leila Perrot, Marie Schmit, Gregory Aydin, Selda Chen, Zhiyong Penaloza, Andrea De Greef, Julien Yildiz, Halil Pothen, Lucie Yombi, Jean Cyr Dewulf, Joseph Scohy, Anais Gérard, Ludovic Wittebole, Xavier Laterre, Pierre-François Miller, Sara E. Devuyst, Olivier Jadoul, Michel Morelle, Johann |
author_facet | Werion, Alexis Belkhir, Leila Perrot, Marie Schmit, Gregory Aydin, Selda Chen, Zhiyong Penaloza, Andrea De Greef, Julien Yildiz, Halil Pothen, Lucie Yombi, Jean Cyr Dewulf, Joseph Scohy, Anais Gérard, Ludovic Wittebole, Xavier Laterre, Pierre-François Miller, Sara E. Devuyst, Olivier Jadoul, Michel Morelle, Johann |
author_sort | Werion, Alexis |
collection | PubMed |
description | Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome. |
format | Online Article Text |
id | pubmed-7416689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | International Society of Nephrology. Published by Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74166892020-08-10 SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule Werion, Alexis Belkhir, Leila Perrot, Marie Schmit, Gregory Aydin, Selda Chen, Zhiyong Penaloza, Andrea De Greef, Julien Yildiz, Halil Pothen, Lucie Yombi, Jean Cyr Dewulf, Joseph Scohy, Anais Gérard, Ludovic Wittebole, Xavier Laterre, Pierre-François Miller, Sara E. Devuyst, Olivier Jadoul, Michel Morelle, Johann Kidney Int Clinical Investigation Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome. International Society of Nephrology. Published by Elsevier Inc. 2020-11 2020-08-10 /pmc/articles/PMC7416689/ /pubmed/32791255 http://dx.doi.org/10.1016/j.kint.2020.07.019 Text en © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Clinical Investigation Werion, Alexis Belkhir, Leila Perrot, Marie Schmit, Gregory Aydin, Selda Chen, Zhiyong Penaloza, Andrea De Greef, Julien Yildiz, Halil Pothen, Lucie Yombi, Jean Cyr Dewulf, Joseph Scohy, Anais Gérard, Ludovic Wittebole, Xavier Laterre, Pierre-François Miller, Sara E. Devuyst, Olivier Jadoul, Michel Morelle, Johann SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule |
title | SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule |
title_full | SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule |
title_fullStr | SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule |
title_full_unstemmed | SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule |
title_short | SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule |
title_sort | sars-cov-2 causes a specific dysfunction of the kidney proximal tubule |
topic | Clinical Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416689/ https://www.ncbi.nlm.nih.gov/pubmed/32791255 http://dx.doi.org/10.1016/j.kint.2020.07.019 |
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