Levels of circulating kidney injury markers and IL-10 identify non-critically ill patients with COVID-19 at risk of death

BACKGROUNDAfter identifying 2 immunomarkers of acute injury, KIM-1 and LCN2, in all kidney biopsies from 31 patients with COVID-19 pneumonia and de novo kidney dysfunction, we investigated whether circulating markers of kidney epithelial injury are common in patients with laboratory-confirmed COVID-19 who require oxygen support but do not have critical illness.METHODSWe studied 196 patients admitted to 15 hospitals with moderate to severe pneumonia who were enrolled in 2 independent randomized clinical trials. We measured 41 immune mediators and markers of kidney and endothelial injury in peripheral blood in these patients within 24 hours of randomization.RESULTSWe constructed a generalized linear CORIMUNO model combining serum levels of KIM-1, LCN2, IL-10, and age at hospital admission that showed high discrimination for mortality (derivation cohort: AUC = 0.82, 95% CI: 0.73-0.92; validation cohort: AUC = 0.83, 95% CI: 0.74-0.92). An early rise in circulating kidney injury markers, in the absence of acute kidney injury criteria, was markedly associated with the risk of developing a severe form of COVID-19 and death within 3 months.CONCLUSIONThe CORIMUNO score may be a helpful tool for risk stratification, and for the first time to our knowledge, it identifies the overlooked impact of subclinical kidney injury on pneumonia outcomes.TRIAL REGISTRATIONClinicalTrials.gov NCT04324047, NCT04324073, and NCT04331808.FUNDINGThis research was funded by the French Ministry of Health, Programme Hospitalier de Recherche Clinique (PHRC COVID-19-20-0151, PHRC COVID-19-20-0029), Fondation de l'Assistance Publique Hôpitaux de Paris (Alliance Tous Unis Contre le Virus), Assistance Publique Hôpitaux de Paris, and grants from the Fondation pour la Recherche Médicale (FRM) (REA202010012514) and Agence Nationale de Recherches sur le Sida and emerging infectious diseases (ANRS) (ANRS0147) from the VINTED sponsorship.

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Journal
JCI Insight
Published
2026-01-22
DOI
https://doi.org/10.1172/jci.insight.198244
Primary Topic
COVID-19 Clinical Research Studies
Type
article
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article

Levels of circulating kidney injury markers and IL-10 identify non-critically ill patients with COVID-19 at risk of death

C. Verstuyft, Jana Biermann, Aurélie Sannier, Olivia May et al.
JCI Insight
COVID-19 Clinical Research Studies
article

Levels of circulating kidney injury markers and IL-10 identify non-critically ill patients with COVID-19 at risk of death

C. Verstuyft, Jana Biermann, Aurélie Sannier, Olivia May, V. Audard, X. Mariette, Guylaine Henry, Thibaut d’Izarny-Gargas, Anissa Moktefi, I. Le Monnier de Gouville, S Ferlicot, Stéphanie Baron, M. Essig, Hassan Izzedine, Xavier Belenfant, Nicola Wanner, A. Couturier, Yannis Lombardi, Tobias B. Huber, Laurence Homyrda, Maxime Dougados, France Mentre, Marine Livrozet, Nassim Mahtal, P. Ravaud, Anouk Walter-Petrich, Florence Morin, Matthieu Jamme, Eric Daugas, Ouifiya Kafif, Léa Resmini, David Buob, Olivia Lenoir, Julien Dang, Benjamin Terrier, Catherine Marie, Alexandre Karras, Ziad A Massy, Victor G Puelles, Jean-Sébastien Hulot, Hélène François, Benjamin Izar, Jade Ghosn, Valentine Piquard, Cedric Laouénan, Olivier Hermine, Yazdan Yazdanpanah, Pierre-Louis Tharaux, Isabelle Brocheriou, Raphaël Porcher
article en

Abstract

BACKGROUNDAfter identifying 2 immunomarkers of acute injury, KIM-1 and LCN2, in all kidney biopsies from 31 patients with COVID-19 pneumonia and de novo kidney dysfunction, we investigated whether circulating markers of kidney epithelial injury are common in patients with laboratory-confirmed COVID-19 who require oxygen support but do not have critical illness.METHODSWe studied 196 patients admitted to 15 hospitals with moderate to severe pneumonia who were enrolled in 2 independent randomized clinical trials. We measured 41 immune mediators and markers of kidney and endothelial injury in peripheral blood in these patients within 24 hours of randomization.RESULTSWe constructed a generalized linear CORIMUNO model combining serum levels of KIM-1, LCN2, IL-10, and age at hospital admission that showed high discrimination for mortality (derivation cohort: AUC = 0.82, 95% CI: 0.73-0.92; validation cohort: AUC = 0.83, 95% CI: 0.74-0.92). An early rise in circulating kidney injury markers, in the absence of acute kidney injury criteria, was markedly associated with the risk of developing a severe form of COVID-19 and death within 3 months.CONCLUSIONThe CORIMUNO score may be a helpful tool for risk stratification, and for the first time to our knowledge, it identifies the overlooked impact of subclinical kidney injury on pneumonia outcomes.TRIAL REGISTRATIONClinicalTrials.gov NCT04324047, NCT04324073, and NCT04331808.FUNDINGThis research was funded by the French Ministry of Health, Programme Hospitalier de Recherche Clinique (PHRC COVID-19-20-0151, PHRC COVID-19-20-0029), Fondation de l'Assistance Publique Hôpitaux de Paris (Alliance Tous Unis Contre le Virus), Assistance Publique Hôpitaux de Paris, and grants from the Fondation pour la Recherche Médicale (FRM) (REA202010012514) and Agence Nationale de Recherches sur le Sida and emerging infectious diseases (ANRS) (ANRS0147) from the VINTED sponsorship.

JCI InsightVol. 11(2)
Université Claude Bernard Lyon 1 (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Universität Hamburg (DE), Université Paris-Est Créteil (FR), Université Paris Cité (FR), Université Paris-Saclay (FR), Columbia University Irving Medical Center (US), Paris-Est Sup (FR), Instituto de Salud Carlos III (ES), Sorbonne Université (FR), Sorbonne Paris Cité (FR), Centre de Recherche des Cordeliers (FR), Hôpital Cochin (FR), Institut thématique Immunologie, inflammation, infectiologie et microbiologie (FR), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Européen Georges-Pompidou (FR), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (FR), University Medical Center Hamburg-Eppendorf (DE), Centre Hospitalier Intercommunal de Poissy (FR), Centre Hospitalier Intercommunal André Grégoire Montreuil (FR), Pitié-Salpêtrière Hospital (FR), Bipar (FR), Centre d'Immunologie et des Maladies Infectieuses (FR), Hôpitaux Universitaires Henri-Mondor (FR), Paris Cardiovascular Research Center (FR), Hôpital Ambroise-Paré (FR), Hôtel-Dieu de Paris (FR), Hôpital Saint-Louis (FR), Hôpital Bichat-Claude-Bernard (FR), Générale de Santé (FR), Sylvester Comprehensive Cancer Center (US), Institut Mondor de Recherche Biomédicale (FR), Bicêtre Hospital (FR), Institut des Maladies Génétiques Imagine (FR), Hôpital Tenon (FR), Centre de Recherche Épidémiologie et Statistique (FR), Columbia University (US)
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COVID-19 Clinical Research Studies
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