Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery

Abstract

Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.

Trial registration: ClinicalTrials.gov NCT00774137.

Figure 1.

Urine IL-18, Urine NGAL, and Plasma NGAL peaked at the first collection (0 to 6 hours). AKI is defined by receipt of acute dialysis or doubling in serum creatinine during the hospital stay. 0 to 6 hours, day 2, and day 3 are the sample collection times after surgery. Urine IL-18 is significant at all time points except day 3. Urine NGAL is significant at all time points except the preoperative (pre-op) and day-3 time points. Plasma NGAL is NS at any time point.

Figure 2.

Quintiles of the first postoperative Urine IL-18 and Urine NGAL had a graded relationship with the risk for severe AKI. Unadjusted P for trend is reported. Risk of AKI is the percentage of AKI cases within each quintile (Q). AKI is defined by either receipt of acute dialysis or evidence of postoperative doubling of the preoperative serum creatinine value.

Figure 3.

(A) First post-operative Urine IL-18, Urine NGAL, and plasma NGAL were all linearly associated with longer lengths of hospital and intensive care unit stay after adjustment for other prognostic factors. (B) First postoperative quintiles of each of the three biomarkers were associated with the duration of mechanical ventilation after surgery after adjustment for other prognostic factors. The adjusted P for trend is reported. Q, quintile.

Figure 4.

Diagnostic performance of the first post-operative value of urine IL-18, urine NGAL, Plasma NGAL and Serum Creatinine for the detection of severe AKI. Receiver-operating characteristic (ROC) curves show the diagnostic performance of the four biomarkers and the table shows the performance of each biomarker at the fifth quintile and the optimal cut point. Severe AKI is defined as the receipt of acute dialysis or the doubling of serum creatinine during hospitalization. Cut, cut point; Sens, sensitivity; Spec, specificity; LR+, positive likelihood ratio; LR-, negative likelihood ratio; PPV, positive predictive value; NPV, negative predictive value.