胰岛素样生长因子结合蛋白-7联合序贯器官衰竭评分可早期预测脓毒症急性肾损伤

Insulin-like growth factor-binding protein-7 combined with sequential organ failure assessment can early predict sepsis associated acute kidney injury

目的探讨脓毒症患者血清生物标志物基质金属蛋白酶组织抑制剂-2(TIMP-2)、胰岛素样生长因子结合蛋白-7(IGFBP-7)、血管生成素-2(Ang-2)水平及临床常规指标对脓毒症急性肾损伤(SAKI)的早期预测价值。方法前瞻性观察性研究,纳入2017年4月至2018年8月经北京大学第三医院急诊收治的69例脓毒症患者,其中28例入院72 h内发生急性肾损伤(AKI),41例未发生AKI。记录患者入院时的一般情况包括序贯器官衰竭评分(SOFA)和急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)及实验室检查指标白细胞(WBC)、中性粒细胞/淋巴细胞比值(NLR)、降钙素原(PCT)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、D-二聚体、纤维蛋白原(Fib)、尿素、尿酸,收集患者入院时的血清标本,检测TIMP-2、IGFBP-7、Ang-2水平。用多因素Logistic回归模型分析SAKI发生的危险因素,用受试者工作特征(ROC)曲线下面积(AUC)评估生物标志物及临床常规指标对SAKI的早期预测价值。结果与脓毒症非AKI组比较,脓毒症AKI组的SOFA、脓毒症严重程度、NLR、PCT、CRP、D-二聚体、尿酸水平均较高(P均<0.05);脓毒症AKI组生物标志物TIMP-2、IGFBP-7、TIMP-2×IGFBP-7、Ang-2水平分别为23.5(17.3,30.3)ng/ml、(185.6±47.2)ng/ml、3.98(2.89,6.00)(ng/ml)^(2)/1000、1953(950,2239)pg/ml均高于非AKI组[分别为16.4(13.5,22.4)ng/ml、(139.4±34.7)ng/ml、2.28(1.57,4.03)(ng/ml)^(2)/1000、576(334,1076)pg/ml;P均<0.05];多因素Logistic回归分析显示IGFBP-7(OR=1.039,95%CI 1.000~1.079,P<0.05)、SOFA评分(OR=1.521,95%CI 1.144~2.022,P<0.05)是SAKI的独立危险因素;ROC曲线分析显示,IGFBP-7、SOFA评分早期预测SAKI的AUC分别为0.805(敏感度78.6%,特异度78.3%)、0.832(敏感度67.9%,特异度82.9%),二者联合检测的AUC为0.893(敏感度82.1%,特异度87.8%),且优于2个指标单独的预测价值(P均<0.05)。结论IGFBP-7、SOFA升高是脓毒症患者发生AKI的独立危险因素,二者联合检测有助于早期发现SAKI的高风险人群。

Objective To explore the predictive value of serum tissue inhibitor of metalloproteinases-2(TIMP-2),insulin-like growth factor-binding protein-7(IGFBP-7),angiopoietin-2(Ang-2)and laboratory examination indicators in patients with sepsis associated acute kidney injury(SAKI).Methods Present study included 69 patients with sepsis,who were admitted to the emergency department of Peking University Third Hospital from April 2017 to August 2018.Within 72 hours of admission,28 cases developed SAKI.General clinical features including sequential organ failure assessment(SOFA),acute physiological and chronic health status score Ⅱ(APACHEⅡ)and laboratory examination indicators including white blood cells(WBC),neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT),C-reactive protein(CRP),interleukin-6(IL-6),D-dimer,fibrinogen(Fib),urea,uric acid(UA)were analyzed and serum samples were obtained to detect the levels of biomarkers TIMP-2,IGFBP-7,and Ang-2.Multivariate logistic regression analysis was performed to determine independent risk factors of SAKI,and the receiver operating characteristic(ROC)area under the curve(AUC)was used to assess the early predictive value of biomarkers and laboratory examination indicators for SAKI.Results Compared with the non-SAKI group,patients in the SAKI group had higher SOFA score,higher incidence of septic shock,higher NLR,PCT,CRP,D-dimer,and UA levels(all P<0.05).The levels of TIMP-2,IGFBP-7,TIMP-2×IGFBP-7 and Ang-2 in the SAKI group were 23.5(17.3,30.3)ng/ml,(185.6±47.2)ng/ml,3.98(2.89,6.00)(ng/ml)^(2)/1000,1953(950,2239)pg/ml respectively,which were significantly higher than those in the non-SAKI group(16.4[13.5,22.4]ng/ml,[139.4±34.7]ng/ml,2.28[1.57,4.03](ng/ml)^(2)/1000,576[334,1076]pg/ml,respectively,all P<0.05).Logistic regression analysis showed that IGFBP-7(OR=1.039,95%CI 1.000-1.079,P<0.05)and SOFA(OR=1.521,95%CI 1.144-2.022,P<0.05)are independent risk factors of SAKI.ROC curve analysis showed that the AUC of IGFBP-7 and SOFA scores for early prediction of SAKI was 0.805(sensitivity 78.6%,specificity 78.3%),0.832(sensitivity 67.9%,specificity 82.9%)respectively.Combined both biomarkers,the AUC increased to 0.893(sensitivity 82.1%,specificity 87.8%),the diagnostic performance was superior to IGFBP-7 or SOFA alone(P<0.05).Conclusion Elevated IGFBP-7 and SOFA are independent risk factors for sepsis associated acute kidney injury,and combined assessment with IGFBP-7 and SOFA can increase the diagnostic performance on the early detection of high-risk patients with SAKI.