Urine Biomarkers of Tubular Renal Cell Damage for the Prediction of Acute Kidney Injury After Cardiac Surgery-A Pilot Study

OBJECTIVE To evaluate the perioperative course of urine levels of the renal damage biomarkers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) and to evaluate the predictive value of elevated TIMP-2 \times IGFBP7 concentrations to predict acute kidney injury (AKI) early after cardiac on-pump surgery. DESIGN Prospective, observational cohort study. SETTING University hospital. PARTICIPANTS The study comprised 110 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) between January and March 2014. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Urinary TIMP-2 \times IGFBP7 levels were quantified using a commercially available kit at the following measurement points: before surgery, 1 hour after starting CPB, 4 hours after weaning from CPB, and 24 hours after weaning from CPB (time points 1-4). Postoperative AKI was defined according to Kidney Disease Improving Global Outcomes criteria. AKI after cardiac surgery was diagnosed in 9 patients (8%). The perioperative course of TIMP-2 \times IGFBP7 was significantly different in patients with and without postoperative AKI (p \textless 0.001). TIMP-2 \times IGFBP7 levels were significantly higher in patients with AKI 1 hour after CPB start and 24 hours after weaning from CPB (p \textless 0.05). TIMP-2 \times IGFBP7 levels \textgreater0.40 (ng/mL)(2)/1,000 measured at 1 hour after starting CPB were found to be the optimal cut-off, with a sensitivity of 0.778 and a specificity of 0.641. The negative predictive value was 0.972. CONCLUSIONS Urine levels of TIMP-2 \times IGFBP7 are predictive for AKI at an early time point (1 hour after starting CPB). Renal damage biomarkers such as TIMP-2 and IGFBP7 might be recommended as a supplement to traditionally used criteria of AKI prediction.