Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients.

Abstract

Labile iron appears to play a role in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase--associated lipocalin (NGAL) and hepcidin are involved in iron metabolism and are both upregulated during renal stress. However, in patients at risk, the highest levels of urinary NGAL are associated with AKI severity but the highest urinary hepcidin levels are associated with absence of AKI. We aimed to investigate the value of combining both biomarkers to estimate the severity and progression of AKI in ICU patients.Urinary NGAL and hepcidin were quantified within 48 hours of ICU admission in critically ill patients with the systemic inflammatory response syndrome and early signs of kidney dysfunction (oliguria for ≥2 hours and/or a 25 μmol/L creatinine rise from baseline). Diagnostic and prognostic characteristics were assessed by logistic regression and receiver operating characteristics (ROC) analysis.Of 102 patients, 26 had mild AKI and 28 patients had severe AKI on admission. Sepsis (21%), cardiac surgery (17%) and liver failure (9%) were the primary reasons for ICU admission. NGAL increased (P=0.03) whereas hepcidin decreased (P=0.01) with increasing AKI severity. The value of NGAL/hepcidin ratio to detect severe AKI was higher than when NGAL and hepcidin were used individually and persisted after adjusting for potential confounders (adjusted OR 2.40, 95% CI 1.20--4.78). The ROC areas for predicting worsening AKI were 0.50, 0.52 and 0.48 for NGAL, 1/hepcidin and the NGAL/hepcidin ratio, respectively.The NGAL to hepcidin ratio is more strongly associated with severe AKI than the single biomarkers alone. NGAL and hepcidin, alone or combined as a ratio, were unable to predict progressive AKI in this selected ICU cohort.