尿NGAL、KIM-1对晚期肝硬化肝肾综合征患者的预测价值

Predictive value of urinary NGAL and KIM-1 in patients with hepatorenal syndrome with advanced cirrhosis

目的:探讨尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)及肾脏损伤因子-1(KIM-1)对晚期肝硬化肝肾综合征(HRS)患者的预测价值。方法:选择74例晚期肝硬化患者作为研究对象,所有患者进行12周随访,按照HRS诊断标准分为肝硬化组53例和肝硬化合并HRS(HRS组)21例,所有患者入院后第2 d抽取静脉血和尿液标本,常规检测血液生化指标、肝功能与肾功能生化参数,采用酶联免疫吸附试验检测血清Cys C、NGAL、NAG、IL^(-1)8和尿NGAL、IL^(-1)8、KIM-1、LFABP水平,利用受试者工作曲线(ROC)研究尿NGAL、KIM-1对晚期肝硬化HRS的预测价值。结果:肝硬化组和HRS组性别、年龄、血清肌酐、丙氨酸转氨酶、24 h尿蛋白排泄量等比较差异无统计学意义(P>0.05),HRS组白细胞计数、血小板计数、球蛋白、总胆红素、天冬氨酸转氨酶、Child-Pugh评分明显高于肝硬化组,白蛋白明显低于肝硬化组,两组间比较差异具有统计学意义(P<0.05)。肝硬化组和HRS组血清NAG、IL^(-1)8比较差异无统计学意义(P>0.05),HRS组血清NGAL、Cys C和尿NGAL、KIM-1、LFABP、IL^(-1)8明显高于肝硬化组,两组间比较差异具有统计学意义(P<0.05)。多因素分析显示,尿NGAL、KIM-1、LFABP是影响HRS的独立危险因素(均P<0.05)。ROC曲线分析显示,尿NGAL最佳临界值为18.83μg·L^(-1),预测HRS的曲线下面积(AUC)为0.913(95%CI:0.851~0.975,P<0.05),尿KIM-1最佳临界值为1.72μg·L^(-1),预测HRS的AUC为0.957(95%CI:0.918~0.996,P<0.05),尿LFABP最佳临界值为5.02μg·L^(-1),预测HRS的AUC为0.702(95%CI:0.593~0.811,P<0.05),尿NGAL、KIM-1预测HRS的AUC高于尿LFABP。结论:尿NGAL、KIM-1可以作为预测晚期肝硬化合并HRS的指标之一。

Objective： To explore the predictive value of urinary NGAL and KIM-1 in patients with hepatorenal syndrome with advanced cirrhosis. Methods： A total of 74 cases of advanced cirrhosis patients were selected as research object,all patients were followed up for 12 weeks. According to the HRS criteria,the patients were divided into two groups： cirrhosis group 53 cases and cirrhosis with HRS（ HRS group） 21 cases,venous blood and urinary sample was collected on the 2nd day after admission,blood biochemical parameters,liver function and biochemical parameters were measured,the levels of serum Cys C,NGAL,NAG,IL-18 and urine NGAL,IL-18,KIM-1,LFABP were detected by enzyme linked immunosorbent assay,the predictive value of urinary NGAL and KIM-1 in hepatorenal syndrome with advanced cirrhosis were performed by ROC curves. Results： The gender,age,serum creatinine,alanine aminotransferase,24 h urinary protein excretion in cirrhosis group and HRS group had no significant difference（ P〉0. 05）,white blood cell count,platelet count,globulin,total bilirubin,aspartate aminotransferase,Child-Pugh score in HRS group was significantly higher than that in cirrhosis group,respectively; albumin in HRS group was significantly lower than that in cirrhosis group,the difference between the two groups was statistically significant（ P〈0. 05）. Serum NAG and IL-18 in cirrhosis group and HRS group was not significantly different（ P〉0. 05）,serum NGAL,Cys C and urine NGAL,KIM-1,LFABP,IL-18 in HRS group were significantly higher than those in cirrhosis group,the difference between two groups was statistically significant（ P〈0. 05）. Multivariate analysis showed that urinary NGAL,KIM-1 and LFABP were independent risk factors for HRS（ All P〈0. 05）. ROC curve analysis showed that the optimal critical value of NGAL was 18. 83 μg·L^-1,the area under the curve（ AUC） was 0. 913（ 95% CI： 0. 851 - 0. 975,P〈0. 05）,the optimal critical value of KIM-1 was 1. 72 μg·L^-1,AUC was 0. 957（ 95% CI： 0. 918 - 0. 996,P〈0. 05）,the optimal critical value of LFABP was 5. 02 μg·L^-1,AUC was 0. 702（ 95% CI： 0. 593 - 0. 811,P〈0. 05）,the AUC of predictive value of urinary NGAL and KIM-1 was higher than that of urinary LFABP. Conclusion： Urinary NGAL and KIM-1 can be used as one of the predictors of HRS in patients with advanced cirrhosis.