François Dépret1, Alexa Hollinger2, Alain Cariou3, Nicolas Deye4, Antoine Vieillard-Baron5, Marie-Céline Fournier6, Samir Jaber7, Charles Damoisel8, Qin Lu9, Xavier Monnet10, Isabelle Rennuit11, Michael Darmon12, Marc Leone13, Bertrand Guidet14, Romain Sonneville15, Philippe Montravers16, Sébastien Pili-Floury17, Jean-Yves Lefrant18, Jacques Duranteau19, Pierre-François Laterre20, Nicolas Bréchot9, Haikel Oueslati21, Bernard Cholley22, Joachim Struck23, Oliver Hartmann24, Alexandre Mebazaa25, Etienne Gayat8, Matthieu Legrand26. 1. Groupe Hospitalier Saint-Louis Lariboisiere et Fernand-Widal, 26934, Paris, France. 2. Universitatsspital Basel, 30262, Basel, Switzerland. 3. Hopital Cochin, 26935, Paris, France. 4. University Hospital Saint Louis - Lariboisière, Paris, France. 5. Ambroise Paré University Hosptial, AP-HP, Boulogne-Billancourt, France. 6. Groupe hospitalier Lariboisiere Fernand-Widal, 26934, Paris, France. 7. University hospital. CHU de MONTPELLIER HOPITAL SAINT ELOI, Intensive Care Unit and transplantation-Departement of Anesthesiology DAR B, Montpellier Cedex 5, France. 8. University Hospital Saint Louis - Lariboisière, Department of Anesthesiology and Critical Care Medicine, Paris, France. 9. Piitié-Salpêtrière University Hospistal, Paris, France. 10. Bicetre Hospital, Paris-South University Hospitals, Medical Intensive Care Unit, Le Kremlin-Bicetre, France. 11. Hopital Beaujon, 55100, Clichy, France. 12. Hôpital Saint Louis Paris - APHP, France, Paris, France. 13. Assistance Publique Hôpitaux de Marseille, Hôpital Nord, anesthésie et réanimation, Marseille, France. 14. Hoptal Saint Antoine, Paris, France. 15. AP-HP, Bichat Hospital, Medical and infectious dieases Intensive Care Unit, Paris Diderot university, Paris, France. 16. Assistance Publique - Hopitaux de Paris, 26930, Département d'anesthésie-réanimation, Paris, France. 17. CHU Besancon, 55049, Department of Anesthesiology and Intensive Care Medicine, Besançon University Hospital, Besançon, France EA 3920, University of Bourgogne Franche-Comté, Besançon, France, Besancon, France. 18. Centre Hospitalier Universitaire de Nimes, 36672, ICU, Nimes, France. 19. Bicêtre University Hospital, Anesthesia and Intensive Care Department, Le Kremlin-Bicêtre, France. 20. Department of Critical Care Medicine, St. Luc University Hospital, Université Catholique de Louvain (UCL), Brussels, Belgium. 21. Groupe hospitalier Lariboisiere Fernand-Widal, 26934, Department of Anesthesiology and Critical Care and Burn Unit, Paris, France. 22. HEGP, AP-HP, Paris, France. 23. Sphingotec GmbH, Henningsdorf, Germany. 24. Sphingotec GmbH, Hennigsdorg, Germany. 25. University Paris Diderot, Paris, France. 26. UCSF, 8785, Anesthesia and Perioperative care, San Francisco, California, United States; matthieu.m.legrand@gmail.com.
Abstract
RATIONALE: Sub-clinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically ill patients remain however largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function. OBJECTIVE: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid. METHODS: Prospective observational study in intensive care units (ICUs). FROG-ICU enrolled 2087 critically ill patients and AdrenOSS-1 enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e. >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate (eGFR) above 60 mL/min/1.73 m2 at ICU admission. MEASUREMENTS AND MAIN RESULTS: 6.1% (122/2004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high eGFR, penKid was associated with higher mortality (adjusted standardized HR 1.4 [1.1-1.8], p=0.010 and HR 1.6 [1.3-1.8], p<0.0001, respectively) after adjustment for age, gender, comorbidities, diagnosis, creatinine, diuresis and study. Patients with sub-AKI had higher mortality compared to no AKI (HR 2.4 [1.5-3.7] in FROG-ICU and 2.5 [1.1-5.9] in AdrenOSS-1). CONCLUSION: Sub-AKI defined using penKid occurred in 11.6% to 17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.
RATIONALE: Sub-clinical acute kidney injury (sub-AKI) refers to patients with low serum creatinine but elevated alternative biomarkers of AKI. Its incidence and outcome in critically illpatients remain however largely unknown. Plasma proenkephalin A 119-159 (penKid) has been proposed as a sensitive biomarker of glomerular function. OBJECTIVE: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid. METHODS: Prospective observational study in intensive care units (ICUs). FROG-ICU enrolled 2087 critically illpatients and AdrenOSS-1 enrolled 583 septic patients. The primary endpoint was 28-day mortality after ICU admission. Sub-AKI was defined by an admission penKid concentration above the normal range (i.e. >80 pmol/L) in patients not meeting the definition of AKI. A sensitivity analysis was performed among patients with estimated glomerular filtration rate (eGFR) above 60 mL/min/1.73 m2 at ICU admission. MEASUREMENTS AND MAIN RESULTS: 6.1% (122/2004) and 6.7% (39/583) of patients from the FROG-ICU and AdrenOSS-1 cohorts met the definition of sub-AKI (11.6% and 17.5% of patients without AKI). In patients without AKI or with high eGFR, penKid was associated with higher mortality (adjusted standardized HR 1.4 [1.1-1.8], p=0.010 and HR 1.6 [1.3-1.8], p<0.0001, respectively) after adjustment for age, gender, comorbidities, diagnosis, creatinine, diuresis and study. Patients with sub-AKI had higher mortality compared to no AKI (HR 2.4 [1.5-3.7] in FROG-ICU and 2.5 [1.1-5.9] in AdrenOSS-1). CONCLUSION: Sub-AKI defined using penKid occurred in 11.6% to 17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.
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