Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery

Rajit K. Basu*, Hector R. Wong, Catherine D. Krawczeski, Derek S. Wheeler, Peter B. Manning, Lakhmir S. Chawla, Prasad Devarajan, Stuart L. Goldstein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

143 Scopus citations


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.

OBJECTIVES: 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.

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.

Original languageEnglish (US)
Pages (from-to)2753-2762
Number of pages10
JournalJournal of the American College of Cardiology
Issue number25
StatePublished - Dec 30 2014


  • Acute Dialysis Quality Initiative
  • acute kidney injury phenotypes
  • biomarker combinations
  • cardiac surgery
  • functional acute kidney injury
  • pediatric acute kidney injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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