Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status

Background: The early prediction of acute kidney injury (AKI) by current clinical and laboratory methods remains inadequate. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising non-invasive biomarker of kidney injury. We systematically reviewed the utility of plasma and urine NGAL measurements for the prediction of AKI in humans.

Methods: We searched MEDLINE, PubMed and EMBASE for human biomarker studies that included NGAL (January 2005 to October 2013). Studies reporting on the use of NGAL for the early prediction and prognosis of AKI were analysed in three common clinical settings: cardiac surgery, critical illness and kidney transplantation.

Results: We identified 58 manuscripts that met our inclusion and exclusion criteria, reporting on more than 16,500 patients. Following cardiac surgery, NGAL measurement in over 7000 patients was predictive of AKI and its severity, with an overall area under the receiver operator characteristic curve (AUC) of 0.82-0.83. Similar results were obtained in over 8500 critically ill patients. In over 1000 patients undergoing kidney transplantation, NGAL measurements predicted delayed graft function with an overall AUC of 0.87. In all three settings, NGAL significantly improved the prediction of AKI risk over the clinical model alone.

Conclusions: We identified several studies that collectively strongly support the use of NGAL as a biomarker for the prediction of AKI. However, we noted some limitations, including lack of published studies that adhere to diagnostic study guidelines, heterogeneity in AKI definition, the lack of uniformly applicable cut-off values and variability in the performance of commercially available NGAL assays.