Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin superfamily initially found in activated neutrophils, in relation with its role as an innate antibacterial factor.
The lipocalins are a family of proteins which transport small hydrophobic molecules such as steroids, bilins, retinoids, and lipids. It has been found that a subset of the lipocalins can also exert certain immunomodulatory effects. Lipocalins share limited regions of sequence homology and common tertiary structure architecture.

For which disease and what is the level of evidence?

Acute kidney injury (AKI), is a rapid loss of renal function due to damage to the kidneys, resulting in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products that are normally excreted by the kidney. Depending on the severity and duration of the renal dysfunction, this accumulation is accompanied by metabolic disturbances, such as metabolic acidosis and hyperkalaemia, changes in body fluid balance, and effects on many other organ systems.
Early diagnosis of acute kidney injury (AKI) is often problematic, due to the lack of suitable early biomarkers of renal damage and kidney function.
NGAL appears as an early marker of AKI and two automated assays from two different IVD companies, one using whole blood and the other urine, will be released for the early detection of AKI.

More and more recent articles in peer-reviewed journals confirmed the evidence of NGAL for early detection of AKI.
Mishra et al. (lancet 2005) have studied 71 children undergoing cardiopulmonary bypass and analyzed serial urine and blood samples for NGAL expression. By multivariate analysis, the amount of NGAL in urine at 2 h after cardiopulmonary bypass was the most powerful independent predictor of acute renal injury suggesting that NGAL may represent a sensitive, specific, and highly predictive early biomarker for acute renal injury after cardiac surgery.
In Critical Care in 2007, Dent et al., have studied NGAL plasma levels in 120 children undergoing cardiac surgery and defined AKI (which was defined as a 50% or greater increase in serum creatinine) as the primary outcome of the study. The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine (r = 0.46, P < 0.001), duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P < 0.001). In this study, plasma NGAL appeared as an early predictive biomarker of AKI, morbidity, and mortality after pediatric CPB.
Another study from Malysko et al. (Nephrology 2008) has evaluated serum, urinary NGAL, cystatin C and estimated glomerular filtration rate in hypertensive, normotensive patients with stable coronary heart disease and healthy volunteers. Hypertension is associated with kidney injury as reflected by elevated serum NGAL and cystatin C and authors suggested that NGAL needs to be investigated as a potential early marker for impaired kidney function/kidney injury, especially in patients with another risk factor for kidney damage, namely coronary artery disease.
Makris et al. (CCLM 2009) studied urinary NGAL levels as a predictor of early AKI (first 5 days after injury) in multi-trauma patients. Urinary NGAL was measured using an ELISA technique upon admission and at 24 and 48 h and the presence of AKI was defined by the risk injury failure loss and end-stage kidney classification (RIFLE) criteria. In this study, authors highlighted that urinary NGAL can be used from the 1st day of injury as a reliable predictor of early AKI in multi-trauma patients.
In 2009, Haase-Fielitz et al., have studied NGAL and Cystatin serum concentrations in one hundred adult cardiac surgical patients on arrival in the intensive care unit and at 24 hours postoperatively. The authors assessed have assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). The conclusion of this study was taht early postoperative measurement of serum NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery.

Perspectives

NGAL seems to be a reliable marker to predict acute kidney injury both with urine or blood samples. The incoming challenges for this biomarkers will be related to the analytical performances of the assay (precision, linearity, detection limits, cross-reactivities, reference ranges for different populations), to its potential place in our daily practice and to the success encountered with physicians, to the cost effectiveness of implementation of NGAL and to the validation of NGAL as a screening marker of AKI for populations with high risk of kidney diseases like diabetic patients.

Email address: gruson_damien@yahoo.fr