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

TL;DR

This study shows that kidney injury markers and IL-10 levels in blood can predict death risk in non-critically ill COVID-19 patients.

Contribution

The study introduces a new risk prediction model (CORIMUNO) that highlights the role of subclinical kidney injury in predicting mortality in non-critical COVID-19 patients.

Findings

The CORIMUNO model combining KIM-1, LCN2, IL-10, and age showed high accuracy in predicting mortality in non-critically ill patients.

Early increases in kidney injury markers were strongly linked to severe disease progression and death.

Kidney-derived proteins and IL-10 levels were significantly associated with mortality, even without overt kidney injury.

Abstract

After 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.

We 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.

We 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.

The 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.

ClinicalTrials.gov NCT04324047, NCT04324073, and NCT04331808.

This 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.

A strong association between kidney-derived proteins and IL-10 levels and mortality supports the notion that the kidney is an overlooked sentinel organ in SARS-CoV-2 pneumonia, even in the absence of overt acute kidney injury.

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