Diagnostic Efficacy of Urinary IGFBP7 and TIMP2 Levels in Early Acute Kidney Injury

Abstract

Background: Acute kidney injury (AKI) is an acute renal insufficiency syndrome, often associated with high morbidity and mortality. Currently, there is a lack of early diagnostic biomarkers. Urine Tissue inhibitor of metalloproteinases 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) serve as markers of G1 cell cycle arrest and foretell AKI development. Therefore, this study aimed to investigate the diagnostic efficacy of these two markers in detecting AKI. Method: We analysed urine and serum samples obtained from the normal control, patients without AKI (NO-AKI), and AKI groups. We assessed the levels of Neutrophil gelatinase-associated lipocalin (NGAL), TIMP2, and IGFBP7 in urine and serum creatinine (Scr) levels utilizing corresponding enzyme linked immunosorbent assay (ELISA) kits. The diagnostic values of urinary NGAL, TIMP2, IGFBP7, and serum Scr were evaluated through receiver operating characteristic (ROC) curve analysis. Moreover, the hypoxia model of renal tubule cells was used to simulate AKI in vitro, and the expression levels of TIMP2 and IGFBP7 were determined at different time following hypoxia induction. Results: There were significant differences in urinary TIMP2, IGFBP7, and NGAL levels as well as Scr levels among the three experimental groups. The urinary TIMP2, IGFBP7, and NGAL levels, as well as Scr levels were significantly higher in the AKI group than those in the normal and the NO-AKI groups (p < 0.01). However, the urinary IGFBP7 and Scr levels were elevated in NO-AKI group compared to the normal group. Moreover, there was no substantial difference in urinary TIMP2 and NGAL levels between the NO-AKI and normal groups (p > 0.05). Additionally, ROC curve analysis revealed that the urinary IGFBP7 had excellent diagnostic performance for AKI, followed by urinary TIMP2, NGAL, and Scr. Furthermore, the TIMP2 and IGFBP7 levels elevated in a time dependent manner, reaching the peak at 120 minutes after hypoxia induction, followed by a gradual decline (p < 0.001). Conclusions: The present study shows that IGFBP7 and TIMP2 have good diagnostic value for early AKI, which are potential biomarkers for early screening of high-risk AKI patients.