Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients
François Dépret, Alexa Hollinger, Alain Cariou, Nicolas Deye, Antoine Vieillard‐Baron, Marie-Céline Fournier, Samir Jaber, Charles Damoisel, Qin Lü, Xavier Monnet, Isabelle Rennuit, Michaël Darmon, Marc Léone, Bertrand Guidet, Romain Sonneville, Philippe Montravers, Sébastien Pili‐Floury, Jean‐Yves Lefrant, Jacques Duranteau, Pierre‐François Laterre, Nicolas Bréchot, Haikel Oueslati, Bernard Cholley, Joachim Struck, Oliver Hartmann, Alexandre Mebazaa, Étienne Gayat, Matthieu Legrand
Abstract
Abstract Rationale 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.