During the study period, a total of 861 OHCA patients were admitted to the emergency room, and 97 of them received TTM. After excluding patients without NGAL measurement values and patients with chronic kidney disease, 89 patients (mean age 53.8 years; 63 males [70.8%]) were included in the final study population (Fig. 1).
General Characteristics of Study Participants
The general characteristics (Table 1) were compared between the two study groups, which were stratified by the presence or absence of AKI (AKI (+) group vs AKI (-) group). The AKI (+) group included 48 patients (55.1%). The AKI (-) group included 40 patients (44.9%). There were no significant intergroup differences in the sex distribution, mean age, and presence of underlying diseases. With regard to the initial rhythm, the AKI (+) group showed a significantly higher asystole rate (51.1%), whereas the AKI (-) group showed a higher incidence of ventricular fibrillation (Vf; 66.7%) and pulseless electrical activity (PEA; 23.1%). The rate of witnessed cardiac arrest was higher in the AKI (-) than in the AKI (+) group (92.5% vs 59.2%), whereas significantly higher epinephrine doses were used in the AKI (+) group during CPR. Furthermore, there were no significant intergroup differences with regard to bystander CPR, time from EMS activation to EMS arrival, time from EMS activation to first defibrillation, and time until ROSC. The general characteristics were analysed according to the AKI stage (Additional file 1). In the AKI (+) group, the proportion of stages 1, 2, and 3 AKI was 23.6%, 13.5%, and 18.0% respectively. Compared to the AKI (+) vs AKI (-) group analysis, a similar trend was seen in the AKI stage analysis except for the medical history of diabetes mellitus. With regard to diabetes mellitus, there was no significant difference in the distribution of the incidence in the AKI (+) and AKI (-) groups (p-value 0.202), although there was a significant difference in the distribution of groups by the AKI stages (p=0.025, AKI (-) group, 12.5%; AKI Stage 1, 9.5%; AKI Stage 2, 41.7%: and AKI Stage 3, 37.5%). There was no significant different in baseline creatinine values among the groups stratified by the AKI stage. The peak creatinine level was significantly different according to the AKI stages: 1.35 (95% CI 1.04–1.26) for Stage 1, 2.11 (95% CI 1.99–2.38) for Stage 2, and 4.66 (95% CI 3.70–7.38) for Stage 3.
The intergroup differences in neurologic outcomes at discharge (GNO group vs PNO group) showed that the PNO group (CPC 3–5) included 54 patients (60.7%). There were no significant between-group differences in the sex distribution, mean age, and presence of underlying diseases in the GNO and PNO groups. Similar to the AKI (+) group, the PNO group showed a significantly higher asystole rate (48.1%), whereas the GNO group showed higher rates of Vf (26.9%) and PEA (25.0%). The frequency of witnessed cardiac arrest was higher in the GNO group (91.4% vs 63.0%), whereas time to ROSC was longer in the PNO group (30.5 [14.0–37.3] min vs 16.5 [10.5–29.5] min). The epinephrine dose used in CPR was significantly higher in the PNO group. However, there were no significant differences in bystander CPR, time from EMS activation to EMS arrival, and time from EMS activation to first defibrillation.
Comparison of Clinical Characteristics According to AKI Occurrence and Neurological Outcome
The clinical characteristics were compared according to AKI occurrence and neurological outcome (Table 2). The ROSC-NGAL and 3h-NGAL were significantly higher in the AKI (+) group. In addition, the AKI (-) group showed a significantly higher percentage of survival at discharge (85.0% vs 28.6%). The percentage of poor outcome based on the CPC score was higher in the AKI (+) group (81.6% vs 35.0%). Furthermore, the rates of 1- and 6-month survival were significantly higher in the AKI (-) group (1-month survival: 82.5% vs 28.6%; 6-month survival: 82.5% vs 29.2%; Table 2 and Fig. 2). Furthermore, the clinical characteristics according to the AKI stage were analysed (Additional file 1). Compared to the AKI (+) vs AKI (-) group analysis, a similar trend was observed in the sub-analysis by the AKI stage.
Intergroup comparison of the ROSC-NGAL and 3h-NGAL levels in the groups stratified by the neurologic outcome at discharge showed significantly higher levels of NGAL in the PNO group. The percentage of patients who needed continuous renal replacement therapy was significantly higher in the PNO group (23.1% vs 3.6%), whereas a significantly higher percentage of patients in the GNO group underwent coronary angiography (85.7% vs 18.5%; Table 2 and Fig. 2).
Univariate and Multivariate Logistic Regression Analysis for AKI
To examine the predictors of AKI, we undertook logistic regression analysis to identify the factors that significantly differed between the AKI (+) and AKI (-) groups. The results of multivariate logistic regression analysis showed that unwitnessed cardiac arrest (OR 8.274; 95% CI 1.287–53.18) and 3h-NGAL (OR 1.022; 95% CI 1.009–1.035) were significantly associated with AKI (Table 3).
To examine the predictors of poor neurologic outcome at discharge, we conducted a logistic regression analysis to identify factors that showed significant differences between the good and poor outcome groups. Multivariate logistic regression analysis showed that unwitnessed cardiac arrest (OR 8.357; 95% CI 1.211–57.654) and the higher dose of epinephrine used during CPR (OR 3.348; 95% CI 1.465–7.652) were significantly associated with poor neurologic outcome (Table 3).
ROC Curve and Cut-off Value of NGAL at 3 Hours After ROSC for AKI
A ROC curve analysis was conducted to verify the clinical usefulness of 3h-NGAL as a predictor of AKI. The AUROC of 3h-NGAL for AKI was 0.910 (95% CI 0.830–0.960), whereas the cut-off value was 178 ng/mL. Therefore, the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for AKI were 83.67 (95% CI 70.3–92.7), 90.00 (95% CI 76.3–97.2), 8.37 (95% CI 3.3–21.4), and 0.18 (95% CI 0.10–0.3), respectively. The AUROC of ROSC-NGAL was 0.698 (95% CI 0.591–0.791), which was significantly lower than that of 3h-NGAL (p-value=0.0001; Fig. 3).