Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes

Abstract

In established acute kidney injury (AKI), serum creatinine poorly differentiates prerenal from intrinsic AKI. In this study, we tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) distinguishes between intrinsic and prerenal AKI, and tested its performance in predicting a composite outcome that included progression to a higher RIFLE (Risk, Injury, Failure, Loss of function, End stage renal disease) class, dialysis, or death. Urinary NGAL was measured using a standardized clinical platform in 161 hospitalized patients with established AKI. Sixteen patients were excluded because of postrenal obstruction or insufficient clinical information. Of the remaining 145 patients, 75 had intrinsic AKI, 32 had prerenal AKI, and 38 patients could not be classified. Urinary NGAL levels effectively discriminated between intrinsic and prerenal AKI (area under the receiver-operating characteristic curve 0.87). An NGAL level over 104 μg/l indicated intrinsic AKI (likelihood ratio 5.97), whereas an NGAL level <47 μg/l made intrinsic AKI unlikely (likelihood ratio 0.2). Patients experiencing the composite outcome had significantly higher median urinary NGAL levels on inclusion. In logistic regression analysis, NGAL independently predicted the composite outcome when corrected for demographics, comorbidities, creatinine, and RIFLE class. Hence, urinary NGAL is useful in classifying and stratifying patients with established AKI.

Figures

Figure 1. Study flow diagram

Figure 2. Box plots of biomarker levels in differential diagnosis of AKI and prediction of outcomes

Biomarker levels are presented on a log 10 scale. Boxes indicate median, lower and upper quartiles. Lower and upper whiskers represent data within 1.5 inter-quartile ranges of the lower quartile, and within 1.5 inter-quartile ranges of the upper quartile, respectively, of log 10-transformed biomarker levels. Circles represent outliers.

Figure 3. Urinary NGAL levels and outcomes

Patients were stratified by NGAL level. Percentages of the subgroups that experience aspects of the composite outcome are shown. p for trend is significant for composite and individual clinical outcomes.

Figure 4. Sub-stratification of RIFLE severity classes by NGAL

Patients were stratified by RIFLE severity class (R, I, F) and by NGAL level (cutoff 104 μg/L). Percentages of in-hospital mortality, in-hospital dialysis initiation, or a composite outcome are plotted by RIFLE class and NGAL levels. * p