The effectiveness of urinary TIMP-2 and IGFBP-7 in predicting acute kidney injury in critically ill neonates.

Abstract

Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP-7) and the combination of TIMP-2 and IGFBP-7 ([TIMP-2]•[IGFBP7]) are proposed to be predictive biomarkers for acute kidney injury (AKI). The intention of our study was to determine whether there is any significant predictive value of these biomarkers for the occurrence of AKI and severe AKI in critically ill neonates. Urinary samples were serially collected in 237 neonates during neonatal intensive care unit (NICU) stay for measurements of TIMP-2 and IGFBP-7 in this prospective study. AKI diagnosis was based on KDIGO classification without urine output or serum creatinine >1.2 mg/dL. Twenty neonates developed AKI, including 11 with KDIGO stage 1, defined as mild AKI, and 9 with stages 2 and 3, defined as severe AKI. Urinary IGFBP-7 and [TIMP-2]•[IGFBP7] remained associated with AKI after adjustment for gestational age, gender and illness severity. Urinary [TIMP-2]•[IGFBP7] achieved an AUC of 0.71 (P = 0.034) and displayed a sensitivity of 88.9% and a specificity of 50.9% for discriminating severe AKI at the optimal cut-off value of 0.045. The combination of TIMP-2 and IGFBP-7 had independent discriminative value for severe AKI in critically ill neonates.