The title: Serum neutrophil Gelatinase-associated Lipocalin at 3 hours after return of spontaneous circulation in patients with cardiac arrest and therapeutic hypothermia: Early predictor of acute kidney injury

Background: Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 h after ROSC (3 h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge. Methods: This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 h after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL. Results: Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3 h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009-1.035; p = 0.001). The area under the receiver operating characteristic curve of 3 h-NGAL for AKI was 0.910 (95% CI 0.830-0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3 h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998-1.036; p = 0.084, 3 h-NGAL; OR 0.997; 95% CI 0.992-1.001; p = 0.113). Conclusions: The serum NGAL concentration measured 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.