Combining Functional and Tubular Damage Biomarkers Improves Diagnostic Precision for Acute Kidney Injury After Cardiac Surgery

• Published in: Journal of the American College of Cardiology Vol. 64; no. 25; pp. 2753 - 2762
• Main Authors: Basu, Rajit K., Wong, Hector R., Krawczeski, Catherine D., Wheeler, Derek S., Manning, Peter B., Chawla, Lakhmir S., Devarajan, Prasad, Goldstein, Stuart L.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 30.12.2014; Elsevier; Elsevier Limited
• Subjects: Acute Dialysis Quality Initiative; Acute Kidney Injury - diagnosis; acute kidney injury phenotypes; Acute-Phase Proteins - urine; Biological and medical sciences; biomarker combinations; Biomarkers; Biomarkers - analysis; cardiac surgery; Cardiac Surgical Procedures; Cardiology; Cardiology. Vascular system; Cardiopulmonary Bypass; Cardiovascular; Child, Preschool; Confidence intervals; Creatinine - blood; Cystatin C - blood; Female; functional acute kidney injury; Heart; Hospitals; Humans; Infant; Kidneys; Lipocalin-2; Lipocalins - urine; Male; Medical sciences; Nephrology. Urinary tract diseases; pediatric acute kidney injury; Postoperative Complications - diagnosis; Proto-Oncogene Proteins - urine; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Urinary system involvement in other diseases. Miscellaneous; Acute Dialysis Quality Initiative; LR; pediatric acute kidney injury; uNGAL; AUC; ΔSCr; acute kidney injury phenotypes; CPB; functional acute kidney injury; biomarker combinations; uNGAL+/pCysC; cardiac surgery; pCysC; AKI; CART; urinary neutrophil gelatinase-associated lipocalin; area under the curve; classification and regression tree analysis; plasma cystatin C; likelihood ratio; change in serum creatinine from baseline; cardiopulmonary bypass; biomarker composite designating both >200 ng/mg uNGAL and >0.8 mg/l pCysC; acute kidney injury; Kidney disease; Improvement; Urinary system disease; Acute kidney injury; Biological marker; Cardiovascular disease; Circulatory system; Diagnosis; Cardiac surgery; Cardiology
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2014.09.066

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. 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. 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. 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. Composites of functional and tubular damage biomarkers are superior to ΔSCr for predicting discrete characteristics of AKI.