中性粒细胞明胶酶相关载脂蛋白在早期诊断脓毒症合并急性肾损伤中的价值

The value of neutrophil gelatinase- associated lipocalin in early diagnosis of sepsis complicated by acute kidney injury

目的探讨中性粒细胞明胶酶相关载脂蛋白（NGAL）在早期诊断脓毒症合并急性肾损伤（AKI）中的价值及对脓毒症合并AKI患者预后的评估。方法选择2015—03～2016—02入住贵州医科大学附属医院EICU、MICU，贵阳市金阳医院综合ICU及贵州省肿瘤医院综合ICU脓毒症患者的临床资料，按急性肾损伤网络（AKIN）对AKI的诊断标准统计各组中合并AKI的例数，同时对比AKI组和非AKI组患者入室时及入室后2、6、12、24、48h尿中性粒细胞明胶酶相关载脂蛋白（NGAL）、血肌酐（SCr）、胱抑素（Cys—C）水平，绘制NGAL、SCr、Cys-C诊断AKI的受试者工作特征曲线（ROC曲线）并计算曲线下面积（AUC），寻找NGAL诊断AKI的最佳截断值计算其敏感度、特异度、阳性似然比、阴性似然比及约登指数。比较各观察点NGAL、Cys—C与APACHElI评分相关性。比较AKI组和非AKI组患者相关预后指标。结果①根据尿NGAL、SCr、Cys-C相关数据绘制ROC曲线并计算AUC，尿NGAL的AUC为0．970（95％C10．921～0．991），SCr的AUC为0．788（95％C10．682～0．894），Cys—C的AUC为0．849（95％C10．753～0．945）。NGAL诊断AKI的敏感度为93．1％、特异度为88．6％。选择ROC曲线上尽量靠近左上方的点为最佳临界点，该点所对应的尿NGAL浓度为11．42ng／mL，该浓度为尿NGAL对AKI诊断的最佳临界点。②根据患者各观察点NGAL、Cys—C与APACHEⅡ评分相关性的比较得出，AKI诊断相关生物指标与APACHEⅡ评分呈正相关，入室2h尿NGAL与APACHE Ⅱ评分相关系数最高。入室2hAPACHEⅡ评分与血Cys—C、尿NGAL相关系数分别为0．573、0．859，差异有统计学意义（P〈0．05）。③通过比较AKI组与非AKI组患者相关预后指标得出，AKI组患者住院时间、ICU滞留时间明显延长，28d存活率降低，差异有统计学意义（P〈0．05）。结论尿NGAL较SCr、Cys—C能更早地诊断脓毒症患者AKI的发生，其诊断价值优于SCr、Cys—C。AKI的发生影响脓毒症患者的预后，并发AKI的脓毒症患者住院时间、ICU滞留时间更长，28d存活率更低。

Objective To investigate the value of nuetrophil gelatinase-associated lipocalin （NGAL） in early diagnosis of sepsis complicated by acute kidney injury （AKI）, and to provide prognostic assessment of the patients with sepsis complicated by AKI. Methods We conducted a retrospective analysis of the clinical data of the sepsis patients who were admitted to the Guizhou Medical University Affiliated Hospital EICU and MICU, the ICU of Jinyang Hospital and ICU of Guizhou Cancer Hospital from March 2015 to February 2016, and then divided the patients according to their conditions into the sepsis group and the serious sepsis group. According to the diagnostic criteria of AKIN for diagnosing AKI, the author added up the cases of patients with complicated AKI from each group, meanwhile compares the lev- els of urinary NGAL, SCr and Cys-C of the patients from AKI group and non-AKI group upon the entry into the laboratory, 2, 6, 12, 24 and 48 hours after the entry into the laboratory respectively. We calculated the area under the curve （AUC） of receiver operator characteristic curve （ROC curve）, and the optimal cutoff value of diagnosis of AKI with NGAL, and then calculated its sensitivity, specificity, positive likeli- hood ratio, negative likelihood ratio and Youden＇ s index. We compared the score correlation of NGAL, Cys-C and APACHE Ⅱ from each viewpoint, and compared the related prognostic indicators of the pa- tients from AK1 group and non-AKI group. Results （1）We drew the ROC curve according to the related data of urinary NGAL, SCr and Cys-C, and calculates the AUC. Consequently, the AUC of urinary NGAL was 0.970 （95%CI 0.921 - 0.991）; the AUC of SCr was 0.788 （95%CI 0,682 - 0.894）; and the AUC of Cys-C was 0.849 （95%CI 0.753 - 0.945）. As to the AKI diagnosed by urinary NGAL, its sensitivity was 93.1%; its specificity was 88.6%. We chose the point that was close to the upper left of the ROC curve as possible as the optimal critical point. The corresponding concentration of urinary NGAL of this point was 11.42 ng/mL, which was the value of the optimal critical point of AKI diagnosed by urinary NGAL. （2）According to the comparison of the score correlation of NGAL, Cys-C and APACHE Ⅱ from each viewpoint of the patients, the related biological indicators of AKI diagnosis was positively correlated with the APACHE Ⅱ score. The urinary NGAL and APACHE Ⅱ score-related indicators reached the top two hours after the entry into the laboratory. The related indicators of correlation between the APACHE Ⅱ and the hemal Cys-C, and the correlation between the APACHE Ⅱ and the urinary NGAL was 0.573 and 0.859 respectively. This indicated that the AKI occurrence condition depends on the severity of the sepsis, whieh means the worse condition of the patient was, the higher the AKI occurrence rate would be. （3）Aceording to the comparison of the related prognostic indicators of the patients from AKI group and non-AKI group, it indicated that as the length of stay and ICU residence time of the patients from the AKI group extended evidently, the survival rate of 28 d deereased. The differences were of statistical significance （P 〈 0.05）. It indicated that AKI evidently intervene the prognosis of the patients with sepsis. Enhancing the diagnosis and treatment of the AKI patients can evidently improve the prognosis of the patients with sepsis. Conclusion Compared with SCr and Cys-C, urinary NGAL can diagnose that the AKI happens to the patients with sepsis earlier. Its diagnostic value is higher than that of SCr or Cys-C. The oeeun＇ence of AKI de- pends on the severity of sepsis, and has influence on the prognosis of the patients with sepsis. As the length of stay and ICU residence time of the patients from the AKI group extends, the survival rate of 28 d decreases.