TY - JOUR
T1 - Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery
AU - Basu, Rajit K.
AU - Wong, Hector R.
AU - Krawczeski, Catherine D.
AU - Wheeler, Derek S.
AU - Manning, Peter B.
AU - Chawla, Lakhmir S.
AU - Devarajan, Prasad
AU - Goldstein, Stuart L.
N1 - Funding Information:
This research was supported by National Institutes of Health grants R01-HL08676 , R01-HL085757 , and R01-DK069749 . Dr. Devarajan has reported that he has licensing agreements with Abbott Diagnostics and Alere, Inc., to develop NGAL as a biomarker of kidney injury; and is a consultant for Biosite. All other authors have reported they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2014 American College of Cardiology Foundation.
PY - 2014/12/30
Y1 - 2014/12/30
N2 - 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.
AB - 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.
KW - Acute Dialysis Quality Initiative
KW - acute kidney injury phenotypes
KW - biomarker combinations
KW - cardiac surgery
KW - functional acute kidney injury
KW - pediatric acute kidney injury
UR - http://www.scopus.com/inward/record.url?scp=84919673325&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2014.09.066
DO - 10.1016/j.jacc.2014.09.066
M3 - Article
C2 - 25541128
AN - SCOPUS:84919673325
SN - 0735-1097
VL - 64
SP - 2753
EP - 2762
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 25
ER -