Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery.

Abstract

Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140® meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. A total of 94 infants with a mean age of 154.2 ± 85.7days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47-6.11, p = 0.001). These results demonstration that TIMP-2*IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.