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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 investigate the predictive value of urinary neutrophil gelatinase-associated lipocalin (NGAL) and renal injury factor-1 (KIM-1) in patients with advanced liver cirrhosis and hepatorenal syndrome (HRS). Methods: A total of 74 patients with advanced liver cirrhosis were selected as study subjects. All patients were followed up for 12 weeks. According to the diagnostic criteria of HRS, 53 patients with cirrhosis and 21 patients with cirrhosis complicated with HRS (HRS group) Venous blood and urine samples were collected, blood biochemical parameters, liver function and renal biochemical parameters were detected routinely. Serum levels of Cys C, NGAL, NAG, IL-8 and urinary NGAL were detected by enzyme linked immunosorbent assay (ELISA) (-1) 8, KIM-1, and LFABP were measured. The predictive value of urinary NGAL and KIM-1 on HRS in patients with advanced cirrhosis was determined by receiver operating characteristic curve (ROC) Results: There was no significant difference in gender, age, serum creatinine, alanine aminotransferase, 24 h urinary protein excretion among patients with cirrhosis and HRS (P> 0.05). The white blood cell count, platelet count, globulin, Total bilirubin, aspartate aminotransferase, Child-Pugh score was significantly higher than that of cirrhosis, albumin was significantly lower than the cirrhosis group, the difference between the two groups was statistically significant (P <0.05). Serum levels of NAG and IL-1 in cirrhosis group and HRS group had no significant difference (P> 0.05). Serum levels of NGAL, Cys C and urine NGAL, KIM-1, LFABP and IL- ) 8 was significantly higher than the cirrhosis group, the difference between the 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 best cutoff value of NGAL for urine was 18.83μg · L -1 and the predicted area under curve (AUC) of HRS was 0.913 (95% CI: 0.851-0.975, P <0.05). Urinary KIM- 1 with the best cutoff value of 1.72μg · L -1, the predicted AUC of HRS was 0.957 (95% CI: 0.918-0.996, P <0.05), and the best cutoff value of LFABP was 5.02μg · L ~ (-1) 1). The predicted AUC of HRS was 0.702 (95% CI: 0.593-0.811, P <0.05). The urinary NGAL and KIM-1 predicted the AUC of HRS higher than that of urine LFABP. Conclusion: Urinary NGAL and KIM-1 can be used as predictors of advanced cirrhosis with HRS.