title: Urine hepcidin has additive value in ruling out cardiopulmonary bypass-associated acute kidney injury: an observational cohort study.
abstract: BACKGROUND
  Conventional markers of acute kidney injury (AKI) lack diagnostic accuracy and are expressed only late after cardiac surgery with cardiopulmonary bypass (CPB). Recently, interest has focused on hepcidin, a regulator of iron homeostasis, as a unique renal biomarker.
  
  
  METHODS
  We studied 100 adult patients in the control arm of a randomized, controlled trial http://www.clinicaltrials.gov/NCT00672334 who were identified as being at increased risk of AKI after cardiac surgery with CPB. AKI was defined according to the Risk, Injury, Failure, Loss, End-stage renal disease classification of AKI classification stage. Samples of plasma and urine were obtained simultaneously (1) before CPB (2) six hours after the start of CPB and (3) twenty-four hours after CPB. Plasma and urine hepcidin 25-isoforms were quantified by competitive enzyme-linked immunoassay.
  
  
  RESULTS
  In AKI-free patients (N = 91), urine hepcidin concentrations had largely increased at six and twenty-four hours after CPB, and they were three to seven times higher compared to patients with subsequent AKI (N = 9) in whom postoperative urine hepcidin remained at preoperative levels (P = 0.004, P = 0.002). Furthermore, higher urine hepcidin and, even more so, urine hepcidin adjusted to urine creatinine at six hours after CPB discriminated patients who did not develop AKI (area under the curve (AUC) receiver operating characteristic curve 0.80 [95% confidence interval (95% CI) 0.71 to 0.87] and 0.88 [95% CI 0.78 to 0.97]) or did not need renal replacement therapy initiation (AUC 0.81 [95% CI 0.72 to 0.88] 0.88 [95% CI 0.70 to 0.99]) from those who did. At six hours, urine hepcidin adjusted to urine creatinine was an independent predictor of ruling out AKI (P = 0.011). Plasma hepcidin did not predict no development of AKI. The study findings remained essentially unchanged after excluding patients with preoperative chronic kidney disease.
  
  
  CONCLUSIONS
  Our findings suggest that urine hepcidin is an early predictive biomarker of ruling out AKI after CPB, thereby contributing to early patient risk stratification.
authors.affiliation: Department of Nephrology and Hypertension & Endocrinology and Metabolic Diseases, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Haase-Fielitz
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mertens
authors.forename: Michael
authors.initials: M
authors.lastname: Plass
authors.forename: Hermann
authors.initials: H
authors.lastname: Kuppe
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Mark
authors.initials: M
authors.lastname: Westerman
authors.forename: Vaughn
authors.initials: V
authors.lastname: Ostland
authors.forename: John R
authors.initials: JR
authors.lastname: Prowle
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Michael
authors.initials: M
authors.lastname: Haase
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000652:urine; D000368:Aged; D000900:Anti-Bacterial Agents / Q000652:urine*; D023181:Antimicrobial Cationic Peptides / Q000652:urine*; D015415:Biomarkers; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D064451:Hepcidins; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; C578702:HAMP protein, human; D064451:Hepcidins