NGAL和KIM-1检测在儿童脓毒症合并急性肾损伤中的诊断价值

 目的 探讨中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin，NGAL）和肾损伤因子1（kidney injury molecule 1，KIM-1）的检测在脓毒症合并急性肾损伤（acute kidney injury，AKI）患儿诊疗过程中的临床应用价值。方法 采用病例对照研究，按照纳入标准选取2019年1-12月入住复旦大学附属儿科医院PICU的脓毒症患儿82例，按照排除标准去除13例。按入院后是否发生AKI分为脓毒症AKI组28例和脓毒症非AKI组41例。脓毒症AKI组患儿根据治疗过程中是否进行连续性肾脏替代治疗（continuous renal replacement therapy，CRRT）分为脓毒症AKI-CRRT组和脓毒症AKI-非CRRT组。检测脓毒症AKI和非AKI患儿住院后0 h、24 h和72 h的血NGAL、KIM-1、肌酐、胱抑素C（cystatin C，CysC）和视黄醇结合蛋白（retinol-binding protein，RBP）水平，同时监测24 h和72 h的尿量。用非参数检验统计方法分析数据，通过受试者工作特征（receiver operating characteristic，ROC）曲线分析NGAL、KIM-1、肌酐、尿量、CysC、RBP对脓毒症并发AKI的诊断价值。结果 脓毒症AKI组患儿的NGAL、KIM-1、肌酐、CysC水平在0 h、24 h、72 h时均显著高于脓毒症非AKI组（P<0.05）。脓毒症AKI-CRRT组和非CRRT组各时点NGAL、肌酐的水平均高于脓毒症非AKI组（P<0.05）。KIM-1、CysC、RBP、尿量在24 h和72 h时，脓毒症AKI患儿较非AKI患儿有明显差异（P<0.05）。ROC曲线比较显示：脓毒症AKI-CRRT组和非CRRT组0 h时NGAL的AUC面积均最大（分别为0.907和0.951）、灵敏度最高（分别为92%和100%）。脓毒症AKI-CRTT组患儿的肌酐水平在72 h时呈现下降，并且较24 h时肌酐的AUC面积减小、敏感度和特异性均降低（P<0.05）;NGAL和KIM-1水平在24 h显著升高后，至72 h仍维持在较高水平，且NGAL在3个时点、KIM-1在后2个时点均维持良好的诊断效能。结论 NGAL灵敏度较高，可在早期提示AKI的发生。在血液净化的治疗过程中NGAL、KIM-1受干扰因素较少，可为AKI患儿肾功能真实水平的评估提供参考。

The value of NGAL and KIM-1 detection in clinical diagnosis of sepsis with acute kidney injury in children

Objective To investigate the clinical value of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in cases of sepsis with acute kidney injury (AKI) during the diagnosis and treatment of pediatric patients.Methods A case-control study was performed among 82 children diagnosed with sepsis and admitted to the PICU of Children's Hospital,Fudan University between Jan.and Dec.of 2019.Excluding 13 cases,they were divided into 28 cases of sepsis AKI group and 41 cases of sepsis non-AKI group according to the diagnosis of AKI after admission.According to whether continuous renal replacement therapy (CRRT) was performed during the treatment,children in the sepsis AKI group were further divided into sepsis AKI-CRRT group and sepsis AKI-non-CRRT group.Serum NGAL,KIM-1,cystatin C (CysC),retinol-binding protein (RBP) and creatinine in sepsis children with or without AKI were detected at the time points of 0 hour (0 h),24 hours (24 h) and 72 hours (72 h) after admission,respectively.Urine output were monitored at 24 h and 72 h.The levels of nonparametric test statistical method was employed to analyze the data.The diagnostic value of NGAL,KIM-1,creatinine, urine output,CysC and RBP in sepsis with AKI was analyzed by observing the receiver operating curve (ROC).Results In children of sepsis AKI group,the detection values of NGAL,KIM-1,creatinine and CysC at 0 h,24 h and 72 h were significantly higher than those in sepsis non-AKI group (P<0.05).The levels of NGAL and creatinine at each time point in sepsis AKI-CRRT group and non-CRRT group were higher than those in sepsis non-AKI group (P<0.05).Levels of KIM-1,CysC,RBP and urine output at 24 h and 72 h in sepsis AKI group was significantly different from those in sepsis non-AKI group (P<0.05).Comparison of ROC curves showed that the AUC area of NGAL at 0 h in sepsis AKI-CRRT group and non-CRRT group was the largest (0.907 and 0.951,respectively),and the sensitivity was the highest (92% and 100%,respectively).The creatinine level of sepsis AKI-CRRT group treatment decreased at 72 h,and the AUC area of creatinine at 72 h was lower than that at 24 h,and the sensitivity and specificity decreased (P<0.05).While NGAL and KIM-1 levels increased significantly at 24 h,then remained high at 72 h.NGAL at the 3 time points and KIM-1 at the last 2 time points maintained good diagnostic performance.Conclusion NGAL has high sensitivity and may act as an early indicator for occurrence of acute kidney injury. Due to their less interference during the treatment of blood purification,NGAL and KIM-1 may help to evaluate the true level of renal function in children with AKI.