Value of combined measurement of urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinases-2 in predicting acute kidney injury associated with HBV-related acute-on-chronic liver failure

Objective To perform dynamic measurement of urinary insulin-like growth factor-binding protein 7 ( IFGBP7) and tissue inhibitor of metalloproteinases-2 ( TIMP-2) in patients with HBV-related acute-on-chronic liver failure ( HBV-ACLF) , and to investigate the value of combined measurement of urinary IFGBP7 and TIMP-2 in early prediction of acute kidney injury ( AKI) associated with HBV-ACLF. Methods A total of 61 patients with HBV-ACLF who were admitted to the First Affiliated Hospital of Nanchang University from September 2015 to January 2016 were enrolled, and according to the presence or absence of AKI, they were divided into AKI group with 15 patients and non-AKI group with 46 patients. A total of 21 hospitalized patients with chronic hepatitis B were enrolled as control group. Urine samples were collected at 8∶ 00 and 20∶ 00 every day since the day of admission. For the AKI group, the urine samples collected within 5 days before a confirmed diagnosis of AKI was made were used for analysis, and for the non-AKI group and the control group, the urine samples collected within 5 consecutive days during the same period of time were used for analysis. ELISA was used to measure the levels of IFGBP7 and TIMP-2 in urine, and serum creatinine ( SCr) and estimated glomerular filtration rate ( eGFR) were recorded during the same period of time. The Kruskal-Wallis rank sum test was used for comparison of continuous data between multiple groups; and pairwise compared was made by Wilcoxon test; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups; the receiver operating characteristic ( ROC) curve and the area under the ROC curve ( AUC) were used to evaluate the efficiency of combined measurement of IFGBP7 and TIMP-2 in the diagnosis of AKI. Results For HBV-ACLF patients, the levels of IFGBP7 and TIMP-2 gradually increased from 48 hours before the diagnosis of AKI to the time of diagnosis, and there were significant differences in the levels of IFGBP7 and TIMP-2 between the control group/the non-AKI group and the AKI group at 48 hours to 12 hours before the diagnosis of AKI to the time of diagnosis ( all P < 0. 05) . With the aggravation of disease conditions in the AKI group, at 36 hours before the diagnosis of AKI and at the time of diagnosis, SCr was significantly higher, eGFR was significantly lower than those at baseline ( both P < 0. 05) . The increases in the levels of IFGBP7 and TIMP-2 at 36 hours before the diagnosis of AKI had a high sensitivity in predicting AKI, with an AUC of 0. 896 ( 95% confidence interval: 0. 789-0. 960, P = 0. 043) and a stronger ability of AKI prediction than SCr and eGFR. Conclusion The increases in urinary TIMP-2 and IGFBP-7 can accurately predict AKI in patients with HBV-ACLF.