NGAL: an emerging tool for predicting severity of AKI is easily detected by a clinical assay

Abstract

Expanded AbstractCitationBennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, Devarajan P: Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol 2008, 3:665-673 [1].BackgroundThe 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). The availability of a standardized clinical platform for NGAL measurements could revolutionize renal diagnostics, especially in intensive care situations.MethodsObjectiveThe first objective of the present study was to determine whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT® analyzer, Abbott Diagnostics) correlates with the research-based assay. The second objective was to determine the utility of the standardized NGAL immunoassay as a predictive biomarker of AKI after CPB in a large prospective cohort.DesignProspective cohort studySettingChildren's hospital at a large US academic medical center.Subjects196 children undergoing elective CPB for surgical correction or palliation of congenital heart lesions between January 2004 and June 2006.InterventionNone.OutcomesThe primary outcome variable was the development of AKI, defined as a 50% or greater increase in serum creatinine from baseline. Other outcomes included percent change in serum creatinine, days in AKI, dialysis requirement, length of hospital stay, and mortality.ResultsIn 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, serial urine NGAL measurements were obtained by ARCHITECT assay. Of the 196 children undergoing CPB, 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.ConclusionsAccurate measurements of urine NGAL are obtained using the ARCHITECT® platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.