Research

Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study

Michael Zappitelli^{* 1} , Kimberly K Washburn^{* 1} , Ayse A Arikan¹ , Laura Loftis¹ , Qing Ma² , Prasad Devarajan² , Chirag R Parikh³ and Stuart L Goldstein¹

¹Texas Children's Hospital, Fannin Street, Houston, Texas 77030, USA

²Cincinnati Children's Hospital Medical Center, Burnet Avenue, Cincinnati, Ohio 45229-3039, USA

³Yale University School of Medicine, Campbell Avenue, West Haven, Connecticut 06516, USA

author email corresponding author email* Contributed equally

Critical Care 2007, 11:R84doi:10.1186/cc6089

Published:	2 August 2007

See related commentary by Ronco, http://ccforum.com/content/11/6/173

Abstract

Introduction

Serum creatinine is a late marker of acute kidney injury (AKI). Urine neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of AKI, where the timing of kidney injury is known. It is unknown whether uNGAL predicts AKI in the general critical care setting. We assessed the ability of uNGAL to predict AKI development and severity in critically ill children.

Methods

This was a prospective cohort study of critically ill children. Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible. Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded. Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation. Clinical data and serum creatinine were collected daily for up to 14 days from enrollment, and urine was collected once daily for up to 4 days for uNGAL measurement. AKI was graded using pRIFLE (pediatric modified Risk, Injury, Failure, Loss, End Stage Kidney Disease) criteria. Day 0 was defined as the day on which the AKI initially occurred, and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period. The χ² test was used to compare associations between categorical variables. Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups. Diagnostic characteristics were evaluated by calculating sensitivity and specificity, and constructing receiver operating characteristic curves.

Results

A total of 140 patients (54% boys, mean ± standard deviation Pediatric Risk of Mortality II score 15.0 ± 8.0, 23% sepsis) were included. Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status (P < 0.05). uNGAL concentrations rose (at least sixfold higher than in controls) in AKI, 2 days before and after a 50% or greater rise in serum creatinine, without change in control uNGAL. The parameter uNGAL was a good diagnostic marker for AKI development (area under the receiver operating characteristic curve [AUC] 0.78, 95% confidence interval [CI] 0.62 to 0.95) and persistent AKI for 48 hours or longer (AUC 0.79, 95% CI 0.61 to 0.98), but not for AKI severity, when it was recorded after a rise in serum creatinine had occurred (AUC 0.63, 95% CI 0.44 to 0.82).

Conclusion

We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.