• François Dépret, Alexa Hollinger, Alain Cariou, Nicolas Deye, Antoine Vieillard-Baron, Marie-Céline Fournier, Samir Jaber, Charles Damoisel, Qin Lu, Xavier Monnet, Isabelle Rennuit, Michael Darmon, Marc Leone, Bertrand Guidet, Romain Sonneville, Philippe Montravers, Sébastien Pili-Floury, Jean-Yves Lefrant, Jacques Duranteau, Pierre-François Laterre, Nicolas Brechot, Haikel Oueslati, Bernard Cholley, Joachim Struck, Oliver Hartmann, Alexandre Mebazaa, Etienne Gayat, and Matthieu Legrand.
• Department of Anaesthesiology, Critical Care Medicine and Burn Unit, Saint Louis-Lariboisière University Hospitals, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
• Am. J. Respir. Crit. Care Med. 2020 Sep 15; 202 (6): 822-829.

AbstractRationale: Subclinical 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.Objectives: In this ancillary study of two cohorts, we explored the incidence and outcome of sub-AKI based on penKid.Methods: A prospective observational study in ICUs was conducted. FROG-ICU (French and European Outcome Registry in ICUs) enrolled 2,087 critically ill patients, and AdrenOSS-1 (Adrenomedullin and Outcome in Severe Sepsis and Septic Shock-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 above 60 ml/min/1.73 m2 at ICU admission.Measurements and Main Results: In total, 6.1% (122/2,004) 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 estimated glomerular filtration rate, penKid was associated with higher mortality (adjusted standardized hazard ratio [HR], 1.4 [95% confidence interval, 1.1-1.8]; P = 0.010; and HR, 1.6 [95% confidence interval, 1.3-1.8]; P < 0.0001, respectively) after adjustment for age, sex, comorbidities, diagnosis, creatinine, diuresis, and study. Patients with sub-AKI had higher mortality compared with no AKI (HR, 2.4 [95% confidence interval, 1.5-3.7] in FROG-ICU and 2.5 [95% confidence interval, 1.1-5.9] in AdrenOSS-1).Conclusions: Sub-AKI defined using penKid occurred in 11.6-17.5% of patients without AKI and was associated with a risk of death close to patients with AKI.

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