Urine NGAL Predicts Severity of Acute Kidney Injury After Cardiac Surgery

TLDR

Urine neutrophil‑gelatinase‑associated lipocalin (NGAL) measured by research ELISA has been shown to be an early predictive biomarker of acute kidney injury after cardiopulmonary bypass. This study tested whether a standardized clinical NGAL immunoassay on the ARCHITECT analyzer can predict acute kidney injury after cardiopulmonary bypass. A pilot study of 136 urine samples demonstrated a 0.99 correlation between research ELISA and the ARCHITECT assay, followed by a prospective enrollment of 196 children undergoing CPB with serial urine NGAL measurements obtained by the ARCHITECT platform. Urine NGAL measured 2 h after CPB rose 15‑fold, reached an AUC of 0.95 (sensitivity 0.82, specificity 0.90 at 100 ng/ml), and correlated with AKI severity, duration, length of stay, dialysis need, and mortality, enabling earlier detection than serum creatinine.

Abstract

The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested.In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as a > or = 50% increase in serum creatinine.AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death.Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.