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尿液中IGFBP7和TIMP-2联合检测对HBV相关慢加急性肝衰竭致急性肾损伤的预测价值
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
文章发布日期:2019年06月14日  来源:  作者:李明,陈入溧,吴振平,等  点击次数:210次  下载次数:40次

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【摘要】:目的动态检测HBV相关慢加急性肝衰竭(HBV-ACLF)患者尿液中胰岛素样生长因子结合蛋白7(IGFBP7)和基质金属蛋白酶抑制因子2(TIMP-2)水平,探讨二者联合对HBV-ACLF相关急性肾损伤(AKI)的早期预测价值。方法选取2015年9月-2016年1月入住南昌大学第一附属医院的HBV-ACLF患者61例,根据最终是否发生AKI分成两组:AKI组15例,非AKI组46例;另选取住院的慢性乙型肝炎患者21例作为对照组。从入院开始收集所有患者每天8∶00、20∶00尿液标本,对AKI组选取确诊AKI前5 d的尿液标本,对非AKI组和对照组选取同时间段内连续5 d的尿液标本。采用ELISA方法检测尿液中IGFBP7和TIMP-2的水平,同时记录该时间段内血肌酐(SCr)、估算肾小球滤过率 (eGFR)。计量资料多组间比较采用Kruskal-Wallis H秩和检验,进一步两两比较采用Wilcoxon检验;计数资料组间比较采用χ2检验或Fisher确切概率法;通过受试者工作特征曲线及曲线下面积(AUC)评价IGFBP7×TIMP-2对于AKI的诊断效能。结果HBV-ACLF患者在确诊AKI前48 h IGFBP7×TIMP-2水平开始升高并随时间逐步上升直至确诊AKI时已上升至高表达状态(前24 h),非AKI组、慢性乙型肝炎对照组在确诊AKI前48 h至AKI前12h的IGFBP7×TIMP-2水平与AKI组同时段比较,差异均有统计学意义(P值均<0.05)。AKI组患者随病情加重,AKI前36 h和确诊AKI时的SCr水平均明显高于基线,eGFR水平均明显低于基线(P值均<0.05)。在AKI前36 h IGFBP7×TIMP-2水平的升高对预测AKI的发生有较高的敏感度(AUC=0.896, 95%可信区间: 0.789~0.960,P=0.043),比同一时间点的SCr和eGFR有更高的预测AKI的能力。结论HBV-ACLF患者尿液中TIMP-2×IGFBP-7水平的升高可较为准确地预测AKI的发生。
【Abstract】:ObjectiveTo 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. MethodsA 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. ResultsFor 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. ConclusionThe increases in urinary TIMP-2 and IGFBP-7 can accurately predict AKI in patients with HBV-ACLF.
【关键字】:慢加急性肝功能衰竭; 急性肾损伤; 胰岛素样生长因子结合蛋白质类; 基质金属蛋白酶抑制剂
【Key words】:acute-on-chronic liver failure; acute kidney injury; insulin-like growth factor binding proteins; matrix metalloproteinase inhibitors
【引证本文】:LI M, CHEN RL, WU ZP, et al. 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[J]. J Clin Hepatol, 2019, 35(7): 1560-1564. (in Chinese)
李明, 陈入溧, 吴振平, 等. 尿液中IGFBP7和TIMP-2联合检测对HBV相关慢加急性肝衰竭致急性肾损伤的预测价值[J]. 临床肝胆病杂志, 2019, 35(7): 1560-1564.

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