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SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule.

Publication ,  Journal Article
Werion, A; Belkhir, L; Perrot, M; Schmit, G; Aydin, S; Chen, Z; Penaloza, A; De Greef, J; Yildiz, H; Pothen, L; Yombi, JC; Dewulf, J ...
Published in: Kidney Int
November 2020

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.

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Published In

Kidney Int

DOI

EISSN

1523-1755

Publication Date

November 2020

Volume

98

Issue

5

Start / End Page

1296 / 1307

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • SARS-CoV-2
  • Pneumonia, Viral
  • Pandemics
  • Middle Aged
  • Male
  • Kidney Tubules, Proximal
  • Humans
  • Coronavirus Infections
  • Case-Control Studies
 

Citation

APA
Chicago
ICMJE
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Werion, A., Belkhir, L., Perrot, M., Schmit, G., Aydin, S., Chen, Z., … Cliniques universitaires Saint-Luc (CUSL) COVID-19 Research Group, . (2020). SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule. Kidney Int, 98(5), 1296–1307. https://doi.org/10.1016/j.kint.2020.07.019
Werion, Alexis, Leila Belkhir, Marie Perrot, Gregory Schmit, Selda Aydin, Zhiyong Chen, Andrea Penaloza, et al. “SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule.Kidney Int 98, no. 5 (November 2020): 1296–1307. https://doi.org/10.1016/j.kint.2020.07.019.
Werion A, Belkhir L, Perrot M, Schmit G, Aydin S, Chen Z, et al. SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule. Kidney Int. 2020 Nov;98(5):1296–307.
Werion, Alexis, et al. “SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule.Kidney Int, vol. 98, no. 5, Nov. 2020, pp. 1296–307. Pubmed, doi:10.1016/j.kint.2020.07.019.
Werion A, Belkhir L, Perrot M, Schmit G, Aydin S, Chen Z, Penaloza A, De Greef J, Yildiz H, Pothen L, Yombi JC, Dewulf J, Scohy A, Gérard L, Wittebole X, Laterre P-F, Miller SE, Devuyst O, Jadoul M, Morelle J, Cliniques universitaires Saint-Luc (CUSL) COVID-19 Research Group. SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule. Kidney Int. 2020 Nov;98(5):1296–1307.
Journal cover image

Published In

Kidney Int

DOI

EISSN

1523-1755

Publication Date

November 2020

Volume

98

Issue

5

Start / End Page

1296 / 1307

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • SARS-CoV-2
  • Pneumonia, Viral
  • Pandemics
  • Middle Aged
  • Male
  • Kidney Tubules, Proximal
  • Humans
  • Coronavirus Infections
  • Case-Control Studies