Clinical review: Predictive value of neutrophil gelatinase-associated lipocalin for acute kidney injury in intensive care patients

Peter B Hjortrup,Nicolai Haase,Anders Perner,Mik Wetterslev

doi:10.1186/cc11855

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) may be an early marker of acute kidney injury (AKI), but elevated NGAL occurs in a wide range of systemic diseases. Because intensive care patients have high levels of comorbidity, our objective was to conduct a systematic review of the literature to evaluate the value of plasma and urinary NGAL to predict AKI in these patients. We conducted a systematic electronic literature search of MEDLINE through PubMed, EMBASE, and Cochrane Library for all English language research publications evaluating the predictive value of plasma or urinary NGAL (or both) for AKI in adult intensive care patients. Two authors independently extracted data by using a standardized extraction sheet including study characteristics, type of NGAL measurements, and type of outcome measures. The primary summary measure was area under receiver operating characteristic curve (AuROC) for NGAL to predict study outcomes. Eleven studies with a total of 2,875 (range of 20 to 632) participants were included: seven studies assessed urinary NGAL and six assessed plasma NGAL. The included studies varied in design, including observation period from NGAL sampling to AKI follow-up (range of 12 hours to 7 days), definition of baseline creatinine value, and urinary NGAL quantification method (normalizing to urinary creatinine or absolute concentration). AuROC values for the prediction of AKI ranged from 0.54 to 0.98. Five studies reported AuROC for use of renal replacement therapy ranging from 0.73 to 0.89, and four studies reported AuROC for mortality ranging from 0.58 to 0.83. There were no differences in the predictive values of urinary and plasma NGAL. The heterogeneity in study design and results made it difficult to evaluate the value of NGAL to predict AKI in intensive care patients. NGAL seems to have reasonable value in predicting use of renal replacement therapy but not mortality.

Highlights

Acute kidney injury (AKI) is frequent in critically ill patients admitted to intensive care units (ICUs) and is independently associated with increased morbidity and mortality [1]
Serum creatinine has been the principal marker of acute kidney injury (AKI) even though it is widely acknowledged that serum creatinine (sCr) is not reliable during acute changes in kidney function and varies with gender, age, muscle mass, dietary intake, and hydration status. sCr does not reflect real-time decline in glomerular filtration rate (GFR), because creatinine has to accumulate as a result of a decrease in GFR before increased concentrations are detectable
Nine studies were in general ICU patients, one was in ICU patients with multiple trauma, and one study was in patients with septic shock

Summary

Introduction

Acute kidney injury (AKI) is frequent in critically ill patients admitted to intensive care units (ICUs) and is independently associated with increased morbidity and mortality [1]. Serum creatinine (sCr) has been the principal marker of AKI even though it is widely acknowledged that sCr is not reliable during acute changes in kidney function and varies with gender, age, muscle mass, dietary intake, and hydration status. A real-time marker of AKI may allow the NGAL, known as lipocalin-2 (lcn2), is a 25-kDa protein and member of the lipocalin superfamily [2]. It was named after its expression in neutrophils and found to have bacteriostatic effects by interfering with bacterial siderophore-mediated iron uptake [3]. Differences between plasma and urinary NGAL kinetics are likely because of local synthesis and excretion of NGAL in the distal tubules of the nephron, further supported by a calculated fractional NGAL excretion of more than 100% [11]

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