Incidence and Outcome of Subclinical Acute Kidney Injury Using penKid in Critically Ill Patients

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.