A Preoperative Multimarker Approach to Evaluate Acute Kidney Injury After Cardiac Surgery

Abstract

Objective: To 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.

Design: Prospective, cohort study.

Setting: Single-center tertiary referral hospital.

Participants: The study comprised 1,015 adults undergoing cardiac surgery with cardiopulmonary bypass.

Interventions: CSA-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 results: One 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).

Conclusions: Preoperative 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.

Keywords: acute kidney injury; cardiac surgery; preoperative biomarkers; risk prediction.