title: Urinary neutrophil gelatinase-associated lipocalin to hepcidin ratio as a biomarker of acute kidney injury in intensive care unit patients.
abstract: BACKGROUND
  Labile iron is important in the pathogenesis of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) and hepcidin control iron metabolism and are upregulated during renal stress. However, higher levels of urinary NGAL are associated with AKI severity whereas higher 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 intensive care unit (ICU) patients.
  
  
  METHODS
  Urinary NGAL and hepcidin were quantified within 48 hours of ICU admission in patients with the systemic inflammatory response syndrome and early 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.
  
  
  RESULTS
  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 primary admission diagnoses. 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.
  
  
  CONCLUSIONS
  The NGAL/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.
authors.affiliation: Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia - johan.martensson@austin.org.au.
authors.forename: J
authors.initials: J
authors.lastname: Mårtensson
authors.forename: N J
authors.initials: NJ
authors.lastname: Glassford
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: G M
authors.initials: GM
authors.lastname: Eastwood
authors.forename: H
authors.initials: H
authors.lastname: Young
authors.forename: L
authors.initials: L
authors.lastname: Peck
authors.forename: V
authors.initials: V
authors.lastname: Ostland
authors.forename: M
authors.initials: M
authors.lastname: Westerman
authors.forename: P
authors.initials: P
authors.lastname: Venge
authors.forename: R
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis*; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D003422:Critical Care / Q000379:methods*; D005260:Female; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010361:Patients; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D064451:Hepcidins; C489506:LCN2 protein, human; D000071068:Lipocalin-2