• Tone B Enger, Hilde Pleym, Roar Stenseth, Guri Greiff, Alexander Wahba, and Vibeke Videm.
• Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, NTNU-Norwegian University of Science and Technology, Trondheim, Norway; Department of Cardiothoracic Anesthesia and Intensive Care, St. Olavs University Hospital, Trondheim, Norway.
• J. Cardiothorac. Vasc. Anesth. 2017 Jun 1; 31 (3): 837-846.

ObjectiveTo investigate whether a multimarker strategy combining preoperative biomarkers representing distinct pathophysiologic pathways enhances preoperative risk assessment of acute kidney injury after cardiac surgery (CSA-AKI) and increases knowledge of underlying pathogenesis.DesignProspective, cohort study.SettingSingle-center tertiary referral hospital.ParticipantsThe study comprised 1,015 adults undergoing cardiac surgery with cardiopulmonary bypass.InterventionsCSA-AKI was defined as≥50% increase in serum creatinine concentration, absolute increase≥26 µmol/L, or new requirement for dialysis. Preoperative and perioperative information until hospital discharge was recorded. Preoperative plasma levels of C-reactive protein, terminal complement complex, neopterin, lactoferrin, N-terminal pro-brain natriuretic peptide, and cystatin C were determined using enzyme immunoassays. Biomarkers were selected based on causal hypotheses of underlying mechanisms and were related to inflammatory, hemodynamic, or renal signaling pathways.Measurements And Main ResultsOne hundred patients (9.9%) developed CSA-AKI. Higher baseline plasma concentrations of neopterin and N-terminal pro-brain natriuretic peptide were associated independently with CSA-AKI (p = 0.04 and p<0.001, respectively). Lower baseline plasma lactoferrin concentrations were observed in patients with CSA-AKI (p = 0.05). Compared with clinical risk assessment, addition of these biomarkers provided a slight, but significant, increment in predictive utility (area under the curve 0.81-0.83, likelihood ratio test p<0.001). A net of 12% of patients were reclassified correctly, and improved prediction was demonstrated, especially in patients with intermediate risk (56% correct reclassification).ConclusionsPreoperative hemodynamic, renal, and immunologic function play central roles in the pathogenesis of CSA-AKI. These findings add evidence to the potential of a multimarker approach to improve preoperative prediction of CSA-AKI.Copyright © 2017 Elsevier Inc. All rights reserved.

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