尿IGFBP7及TIMP-2在失代偿期乙型肝炎肝硬化急性肾损伤中的应用价值

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目的:探讨新型生物标志物尿胰岛素样生长因子结合蛋白7(IGFBP7)及组织基质金属蛋白酶抑制剂-2(TIMP-2)在失代偿期乙型肝炎肝硬化急性肾损伤中的应用价值。方法:选取新住院失代偿期乙型肝炎肝硬化患者45例,其中入院时合并AKI 19例(肝硬化-AKI组),无AKI 26例(肝硬化-非AKI组),健康体检者12例(正常对照组),收集晨尿标本,酶联免疫吸附法检测尿IGFBP7与TIMP-2,动态监测肝硬化-非AKI组入院后尿IGFBP7及血肌酐(SCr)。正态分布计量资料组间比较采用n t检验,非正态分布计量资料组间比较采用秩和检验,用受试者工作特征(ROC)曲线及曲线下面积(AUC)评价指标的诊断效能。n 结果:肝硬化-AKI组(n n = 19)尿IGFBP7、尿IGFBP7与TIMP-2乘积(IGFBP7×TIMP-2)均高于非AKI组(n P值均< 0.05);肝硬化-AKI组或非AKI组尿IGFBP7、尿TIMP-2、尿IGFBP7×TIMP-2均显著高于正常对照组(n P值均< 0.01)。尿IGFBP7、尿IGFBP7×TIMP-2诊断AKI的AUC分别为0.703(95%n CI 0.547~0.860)、0.700(95%n CI 0.541~0.859)。肝硬化-非AKI组(n n = 26)住院期间根据SCr变化新诊断AKI 5例(进展组),尿IGFBP7在诊断AKI的2天前已明显升高;进展组(n n = 5)入院时尿IGFBP7浓度高于非进展组(n n = 21)(n P < 0.05)。n 结论:失代偿期乙型肝炎肝硬化患者尿IGFBP7及TIMP-2浓度明显升高,发生AKI时尿IGFBP7与尿IGFBP7×TIMP-2进一步升高;尿IGFBP7具有早期诊断AKI的价值,且可能有预测AKI发生的作用。“,”Objective:To investigate the application value of new urinary biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue matrix metalloproteinase inhibitor-2 (TIMP-2) in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis.Methods:45 newly hospitalized cases with decompensated hepatitis B virus-related liver cirrhosis were selected. Among them, 19 cases were combined with AKI on admission (cirrhosis-AKI group), 26 cases without AKI (cirrhosis-non-AKI group), and 12 healthy cases (normal control group). First-morning urine samples were collected and IGFBP7 and TIMP-2 were detected by enzyme-linked immunosorbent assay (ELISA). Urinary IGFBP7 and serum creatinine (SCr) were dynamically monitored after hospitalization in cirrhosis-non-AKI group. Normally distributed measurement data were compared by t-test, and non-normally distributed measurement data were compared by rank sum test. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic accuracy of the indicators.Results:Urinary IGFBP7, IGFBP7 with TIMP-2 (IGFBP7×TIMP-2) in cirrhosis-AKI group (n n = 19) were equally higher than that of the cirrhosis-non-AKI group (n P < 0.05). Urinary IGFBP7, TIMP-2 and IGFBP7×TIMP-2 in cirrhosis-AKI group or cirrhosis-non-AKI group were significantly higher than those of the normal control group ( n P < 0.01). The AUC of urinary IGFBP7 and urinary IGFBP7×TIMP-2 for diagnosis of AKI were 0.703 (95% CI 0.547-0.860) and 0.700 (95% CI 0.541-0.859), respectively. In the liver cirrhosis-non-AKI group ( n n = 26), 5 cases of AKI were newly diagnosed according to the changes in SCr during hospitalization (progressive group). Urinary IGFBP7 was significantly increased 2 days before the diagnosis of AKI. The concentration of urinary IGFBP7 at admission in the progressive group (n n = 5) was higher than that of the non-progressive group (n n = 21) (n P < 0.05).n Conclusion:Urinary IGFBP7 and TIMP-2 concentrations were significantly increased in patients with decompensated hepatitis B virus-related liver cirrhosis. When AKI occurred, urinary IGFBP7 and IGFBP7×TIMP-2 was further increased. Urinary IGFBP7 is valuable for early AKI diagnosis, and may play a role in predicting AKI occurrence.
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