Tissue Inhibitor of Metalloproteinase 2 and Insulin-Like Growth Factor-Binding Protein 7 in Pediatric Diabetic Ketoacidosis

Abstract Background Diabetic ketoacidosis (DKA) is one of the main causes of end-stage kidney disease (ESKD). Urinary concentration of tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are well known urinary acute kidney injury (AKI) biomarkers. Objectives to determine the level of urinary TIMP-2 and IGFBP7 as markers of acute kidney injury (AKI) in children with T1DM during and after the resolution of diabetic ketoacidosis. Patients and Methods A prospective longitudinal study was conducted over 1 year, where we have included children with T1DM presented to Emergency Department (ED) at Children’ s Hospital, Faculty of Medicine, Ain Shams University, with moderate and severe DKA, where we followed them at presentation and day 14, and determined those who developed AKI and measured urinary TIMP-2 and IGFBP7 to detect it AKI. Results We have included 40 pediatric patients with T1DM with mean (±SD) age of 10.59 ± 2.17 years, with a female predominance (90%). Among our patients, 18 patients (45%) had AKI at presentation, where they had a significantly elevated urinary level of both TIMP-2 and IGFBP7 than without AKI (TIMP-2 (ng/ml):112.58(13.76 - 190.1) versus 33.53 (17.27 - 149.65), IGFBP7(ng/ml) :77.42(0.57 - 164.3) versus 1.41(0.67 - 82.63) (p < 0.001). Follow up at day 14, after recovery from DKA, we had no patients with AKI, with significant decrease in the same urinary biomarkers (TIMP-2(ng/ml) :11.35 (8.13 - 25.03) versus 9.62 (7.67 - 17.02), IGFBP7(ng/ml) :0.94(0.51 - 2.34) versus 0.78 (0.43 - 1.34) (p < 0.005). Conclusion The level of urinary TIMP-2 and IGFBP7 increased in children and adolescent with T1DM who developed AKI at the time of presentation of DKA, and normalized after the resolution of DKA and the recovery from AKI.