title: Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery.
abstract: BACKGROUND
  Increases in serum creatinine (ΔSCr) from baseline signify acute kidney injury (AKI) but offer little granular information regarding its characteristics. The 10th Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) suggested that combining AKI biomarkers would provide better precision for AKI course prognostication.
  
  
  OBJECTIVE
  This study investigated the value of combining a functional damage biomarker (plasma cystatin C [pCysC]) with a tubular damage biomarker (urine neutrophil gelatinase-associated lipocalin [uNGAL]), forming a composite biomarker for prediction of discrete characteristics of AKI.
  
  
  METHODS
  Data from 345 children after cardiopulmonary bypass (CPB) were analyzed. Severe AKI was defined as Kidney Disease Global Outcomes Initiative stages 2 to 3 (≥100% ΔSCr) within 7 days of CPB. Persistent AKI lasted >2 days. SCr in reversible AKI returned to baseline ≤48 h after CPB. The composite of uNGAL (>200 ng/mg urine Cr = positive [+]) and pCysC (>0.8 mg/l = positive [+]), uNGAL+/pCysC+, measured 2 h after CPB initiation, was compared to ΔSCr increases of ≥50% for correlation with AKI characteristics by using predictive probabilities, likelihood ratios (LR), and area under the curve receiver operating curve (AUC-ROC) values [Corrected].
  
  
  RESULTS
  Severe AKI occurred in 18% of patients. The composite uNGAL+/pCysC+ demonstrated a greater likelihood than ΔSCr for severe AKI (+LR: 34.2 [13.0:94.0] vs. 3.8 [1.9:7.2]) and persistent AKI (+LR: 15.6 [8.8:27.5] versus 4.5 [2.3:8.8]). In AKI patients, the uNGAL-/pCysC+ composite was superior to ΔSCr for prediction of transient AKI. Biomarker composites carried greater probability for specific outcomes than ΔSCr strata.
  
  
  CONCLUSIONS
  Composites of functional and tubular damage biomarkers are superior to ΔSCr for predicting discrete characteristics of AKI.
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio; Division of Pediatric Critical Care, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio. Electronic address: rajit.basu@cchmc.org.
authors.forename: Rajit K
authors.initials: RK
authors.lastname: Basu
authors.affiliation: Division of Pediatric Critical Care, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
authors.affiliation: Division of Pediatric Cardiology, Lucile Packard Children's Hospital, Stanford University, Palo Alto, California.
authors.forename: Catherine D
authors.initials: CD
authors.lastname: Krawczeski
authors.affiliation: Division of Pediatric Critical Care, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Wheeler
authors.affiliation: Division of Cardiothoracic Surgery, St. Louis Children's Hospital, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Manning
authors.affiliation: Department of Medicine, Division of Intensive Care Medicine and Division of Nephrology, Veterans Affairs Medical Center, Washington, DC.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.affiliation: Center for Acute Care Nephrology, Cincinnati Children's Hospital and Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldstein
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis*; D000209:Acute-Phase Proteins / Q000652:urine*; D015415:Biomarkers / Q000032:analysis*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D011183:Postoperative Complications / Q000175:diagnosis; D011518:Proto-Oncogene Proteins / Q000652:urine*
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D003404:Creatinine
keywords: Acute Dialysis Quality Initiative; acute kidney injury phenotypes; biomarker combinations; cardiac surgery; functional acute kidney injury; pediatric acute kidney injury