Predictive performance of urine neutrophil gelatinase-associated lipocalin for dialysis requirement and death following cardiac surgery in neonates and infants

Abstract

Background and objectives: Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been shown to accurately predict and allow early detection of AKI, as assessed by an increase in serum creatinine in children and adults. The present study explores the accuracy of uNGAL for the prediction of severe AKI-related outcomes in neonates and infants undergoing cardiac surgery: dialysis requirement and/or death within 30 days.

Design, setting, participants, & measurements: Prospective, observational cohort study conducted in a tertiary referral pediatric cardiac intensive care unit, including 75 neonates and 125 infants undergoing surgery with cardiopulmonary bypass between August 1, 2010, and May 31, 2011. Urine samples were collected before surgery and at median of five time points within 48 hours of bypass. Urine NGAL was quantified as absolute concentration, creatinine-normalized concentration, and absolute excretion rate, and a clusterization algorithm was applied to the individual uNGAL kinetics. The accuracy for the prediction of the outcome was assessed using receiver-operating characteristic areas, likelihood ratios, diagnostic odds ratios, net reclassification index, integrated reclassification improvement, and number needed to screen.

Results: A total of 1176 urine samples were collected. Of all patients, 8% required dialysis and 4% died. Three clusters of uNGAL kinetics were identified, including patients with significantly different outcomes. The uNGAL level peaked between 1 and 3 hours of bypass and remained high in half of all patients who required dialysis or died. The uNGAL levels measured within 24 hours of bypass accurately predicted the outcome and performed best after normalization to creatinine, with varying cutoffs according to the time elapsed since bypass. The number needed to screen to correctly identify the risk of dialysis or death in one patient varied between 1.5 and 2.6 within 12 hours of bypass.

Conclusions: uNGAL is a valuable predictive tool of dialysis requirement and death in neonates and infants with AKI after cardiac surgery.

Trial registration: ClinicalTrials.gov NCT01219998.

Figures

Figure 1.

Variation of the mean urine creatinine–normalized neutrophil gelatinase-associated lipocalin (NGAL) concentration within 48 hours of surgery. All urine creatinine–normalized uNGAL concentrations were included in individual trajectories of variation. Running the algorithm of clusterization on the individual trajectories resulted in three clusters of variation: normal (n=173), severe (n=23), and very severe (n=4) clusters. Mean concentrations are shown using a thick line, and 95% confidence intervals are shown using error bars. Individual trajectories in the very severe cluster are shown using dotted lines and are identified by letters (see Results). Letters in the right panel denote the individual uNGAL trajectories of the patients in the very severe cluster. CBP, cardiopulmonary bypass.