SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule.
COVID-19
kidney
renal Fanconi syndrome
severe acute respiratory syndrome
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
08
05
2020
revised:
14
07
2020
accepted:
16
07
2020
pubmed:
14
8
2020
medline:
24
11
2020
entrez:
14
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32791255
pii: S0085-2538(20)30912-1
doi: 10.1016/j.kint.2020.07.019
pmc: PMC7416689
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1296-1307Investigateurs
Frank Aboubakar
(F)
Souad Acid
(S)
Nadia Amini
(N)
Sarah Bailly
(S)
Christophe Beauloye
(C)
Diego Castanares-Zapatero
(D)
Emmanuel Coche
(E)
Christine Collienne
(C)
Pascale Cornette
(P)
Isabelle De Brauwer
(I)
Mélanie Dechamps
(M)
Florence Dupriez
(F)
Antoine Froidure
(A)
Quentin Garnir
(Q)
Bernhard Gerber
(B)
Benoît Ghaye
(B)
Isabelle Gilard
(I)
Sophie Gohy
(S)
Charles Grégoire
(C)
Philippe Hantson
(P)
Luc-Marie Jacquet
(LM)
Benoit Kabamba
(B)
Shakeel Kautbally
(S)
Nicolas Lanthier
(N)
Fatima Larbaoui
(F)
Giuseppe Liistro
(G)
Frédéric Maes
(F)
Virginie Montiel
(V)
Benny Mwenge
(B)
Sophie Pierard
(S)
Charles Pilette
(C)
Anne Catherine Pouleur
(AC)
Amaury Sogorb
(A)
Peter Starkel
(P)
Hector Rodriguez-Villalobos
(H)
Maximilien Thoma
(M)
Olivier Van Caeneghem
(O)
David Vancraeynest
(D)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Références
N Engl J Med. 2020 Aug 6;383(6):590-592
pubmed: 32402155
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Sci Total Environ. 2020 Aug 15;730:138996
pubmed: 32371230
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Kidney Int. 1986 Jul;30(1):91-8
pubmed: 3528618
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
Hum Mol Genet. 2019 Jun 15;28(12):1931-1946
pubmed: 30590522
J Am Soc Nephrol. 2020 Jun;31(6):1157-1165
pubmed: 32345702
Hum Pathol. 2018 Mar;73:89-101
pubmed: 29309806
Kidney Int. 2020 Aug;98(2):506-507
pubmed: 32505464
Eur Radiol. 2020 Sep;30(9):4903-4909
pubmed: 32314058
Mol Aspects Med. 2013 Apr-Jun;34(2-3):386-95
pubmed: 23506879
Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613
pubmed: 30476243
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
Am J Kidney Dis. 2005 Jan;45(1):88-95
pubmed: 15696447
Kidney Int. 2020 Jun;97(6):1150-1163
pubmed: 32061435
JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
Kidney Int. 2020 Jul;98(1):231-232
pubmed: 32437764
J Gen Virol. 1971 Aug;12(2):161-8
pubmed: 4107843
Emerg Infect Dis. 2004 Feb;10(2):320-6
pubmed: 15030705
J Am Soc Nephrol. 2020 Aug;31(8):1683-1687
pubmed: 32371536
Kidney Int. 2020 May;97(5):829-838
pubmed: 32247631
Kidney Int. 2020 May;97(5):824-828
pubmed: 32204907
Nat Rev Nephrol. 2017 Aug;13(8):455-470
pubmed: 28669993
J Pathol. 2004 Jun;203(2):631-7
pubmed: 15141377
Lancet. 2020 May 16;395(10236):e87-e88
pubmed: 32423587
Kidney Int. 2018 Oct;94(4):701-715
pubmed: 30007527
Lancet. 2020 May 30;395(10238):e99
pubmed: 32442529
Kidney Int. 2020 Jul;98(1):219-227
pubmed: 32327202
Nat Genet. 2004 Sep;36(9):999-1002
pubmed: 15286787
Nat Commun. 2021 May 4;12(1):2506
pubmed: 33947851
Kidney Int. 2020 Jul;98(1):228-231
pubmed: 32471639
J Am Soc Nephrol. 2015 Oct;26(10):2521-33
pubmed: 25636412
Kidney Int. 2020 Aug;98(2):294-309
pubmed: 32709292
Channels (Austin). 2011 Sep-Oct;5(5):410-23
pubmed: 21814048
Physiol Rev. 2019 Jul 1;99(3):1575-1653
pubmed: 31215303
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Kidney Int. 2016 Jan;89(1):58-67
pubmed: 26759048
Cell. 2020 May 14;181(4):905-913.e7
pubmed: 32333836
Pharmaceutics. 2019 Nov 22;11(12):
pubmed: 31766631
Chin Med J (Engl). 2020 May 5;133(9):1039-1043
pubmed: 32118639
Emerg Microbes Infect. 2020 Dec;9(1):991-993
pubmed: 32342724
Nat Rev Immunol. 2020 Jun;20(6):363-374
pubmed: 32346093
Nature. 2020 May;581(7807):215-220
pubmed: 32225176
Nat Commun. 2018 Jan 11;9(1):161
pubmed: 29323117