可溶性血栓调节蛋白及中性粒细胞明胶酶相关脂质运载蛋白早期预测脓毒症相关急性肾损伤的临床研究
Clinical study of soluble thrombomodulin and urinary neutrophil gelatinase-associated lipocalin in early prediction of sepsis-induced acute kidney injury
摘要目的:探讨脓毒症患者血管内皮损伤、肾小管损伤、炎症、凝血等实验室检查指标在脓毒症相关急性肾损伤中的早期诊断价值。方法:对脓毒症患者进行单中心研究。回顾性研究:入组2017年2月至2018年3月武汉大学人民医院重症监护室119例脓毒症患者,将患者分为AKI组和非AKI组,分析入院时可溶性血栓调节蛋白(sTM)、组织性纤溶酶原激活剂及其抑制物(t-PAI-C)、纤维蛋白原降解产物(FDP)、抗凝血酶Ⅲ(AT-Ⅲ)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶降解产物(PIC)、纤维蛋白原(FIB)、D-二聚体(D-Dimer)、凝血酶原时间(PT)、PT国际标准化比值(PT-INR)、降钙素原质量浓度(PCT)、白细胞数(WBC)、中性粒细胞数(Neu#)、血小板计数(PLT),采用受试者工作特征曲线(ROC曲线)分析上述指标对脓毒症相关急性肾损伤预测价值,采用Logistic回归分析法分析脓毒症相关急性肾损伤的危险因素。前瞻性研究:入组2018年4月至2018年9月武汉大学人民医院重症监护室46例脓毒症患者,入院时检测sTM、t-PAI-C、FDP、AT-Ⅲ、TAT、PIC、FIB、D-Dimer、PT-INR、PCT、血清胱抑素C(Cys C)、尿微量白蛋白与肌酐比值(ACR)、尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)、N-乙酰-β-D-氨基葡萄糖苷酶(uNAL)、视黄醇结合蛋白(uRBP),采用受试者工作特征曲线(ROC曲线)分析上述指标对脓毒症相关急性肾损伤预测价值,采用Logistic回归分析法分析脓毒症相关急性肾损伤的危险因素。结果:①入组119例脓毒症患者,脓毒症相关急性肾损伤组(AKI组)与脓毒症非急性肾损伤组(非AKI组)比较,PCT、PT、PT-INR、sTM、D-Dimer差异有统计学意义;PCT、PT、PT-INR、sTM、D-Dimer对脓毒症相关急性肾损伤有较好的预测作用,其中sTM有较高的诊断准确度(AUC=0.857,95%CI:0.790,0.924)和灵敏度(0.644)、特异度(0.918);sTM高表达、慢性肾衰竭病史是脓毒症相关急性肾损伤的危险因素;②入组46例脓毒症患者,AKI组与非AKI组比较,PCT、sTM、Cys C、uNGAL差异有统计学意义;PCT、sTM、Cys C、uNGAL对脓毒症急性肾损伤具有良好的预测作用,其中sTM灵敏度(>0.999)最高,uNGAL特异度(0.800)最高;sTM高表达是脓毒症相关急性肾损伤的危险因素。结论:可溶性血栓调节蛋白、尿中性粒细胞明胶相关脂质运载蛋白分别代表内皮细胞受损、肾小管受损,可溶性血栓调节蛋白高表达是脓毒症急性肾损伤的独立危险因素。
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abstractsObjective:To compare the early diagnostic value of the indicators of endothelial injury, renal injury, inflammation and coagulation in patients with sepsis-induced acute kidney injury (AKI).Methods:A retrospective study was performed on 119 patients with sepsis from February 2017 to March 2018. Lab tests were performed on patients at admission, which included:ing soluble thrombomodulin (sTM), tissue plasminogen activators and inhibitors (t-PAI-C), antithrombin III (AT-III), thrombin-antithrombin (TAT) complex, plasmin-alpha 2, plasmin inhibitor complex (PIC), fibrin degradation product (FDP), fibrinogen (FIB), D-Dimer, prothrombin time (PT), prothrombin time international normalized ratio (PT-INR), procalcitoni (PCT), white blood cell (WBC), neutrophil (Neu), and platelet count (PLT). The receiver-operating characteristic curve was used to analyze the predictive value of the above indicators, and logistic regression analysis was used to analyze the risk factors of sepsis-induced AKI. A prospective study was conducted from April 2018 to September 2018 and 46 patients were enrolled. The lab tests results retrieved including sTM, t-PAI-C, FDP, AT-III, TAT, PIC, FIB, D-Dimer, PT, PCT, serum cystatin C (Cys C), urine albumin (microalbumin) and albumin to creatinine ratio (ACR), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary N-acetyl-beta-glucosaminidase (uNAG), and urinary retinol-binding protein (uRBP). As same with the previous group, the receiver-operating characteristic curve was used to analyze the diagnostic value of the above indicators, and logistic regression Was used to analyze the risk factors of sepsis-induced AKI.Results:(1) In the retrospective study: sTM, D-Dimer, PCT, PT, and PT-INR were statistically different. sTM, D-Dimer, PCT, PT, and PT-INR had a good diagnostic value for septis-induced AKI, among which, sTM had a highest diagnostic value (AUC: 0.857; 95% CI: 0.790, 0.924), better sensitivity (64.4%) and specificity (91.8%). The high expression of sTM and history of chronic kidney disease were independent risk factors for septis-induced AKI.(2) In the prospective study: PCT, sTM , Cys C, and uNGAL were statistically different. PCT, sTM, Cys C, uNGAL showed good predictive features for septis-induced AKI. sTM had the highest sensitivity (>0.999) while uNGAL had the highest specificity (0.800). The high expression of sTM was an independent risk factor for septis-induced AKI. Conclusions:sTM and uNGAL represent endothelial injury and renal tubular injury respectively. sTM is an independent risk factor of sepsis-induced AKI.
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