切换至 "中华医学电子期刊资源库"

中华卫生应急电子杂志 ›› 2020, Vol. 06 ›› Issue (04) : 202 -208. doi: 10.3877/cma.j.issn.2095-9133.2020.04.002

所属专题: 文献

论著

NGAL对脓毒症/脓毒性休克患者预后的预测作用(已撤稿)
张继松1, 王聿明1, 郑彦俊1, 祁星1, 陈培莉1, 史雯1, 陈影1, 杨之涛1, 毛恩强1, 陈尔真1,()   
  1. 1. 200025 上海,上海交通大学医学院附属瑞金医院急诊科
  • 收稿日期:2020-06-28 出版日期:2020-08-18
  • 通信作者: 陈尔真
  • 基金资助:
    国家自然科学基金项目(81772107); 上海市领军人才项目(18411950900); 上海市卫计委重要薄弱学科建设计划(2016ZB0206); 上海申康医院发展中心项目(SHDC12017116); 上海市卫计委中西医结合专项建设重点项目(ZHYY-ZXYJHZX-1-201702); 上海市卫计委面上项目(201640089)

Predictive effect of neutrophil gelatinase-associated apolipoprotein (NGAL) on prognosis in patients with sepsis/septic shock

Jisong Zhang1, Yuming Wang1, Yanjun Zheng1, Xing Qi1, Peili Chen1, Wen Shi1, Ying Chen1, Zhitao Yang1, Enqiang Mao1, Erzhen Chen1,()   

  1. 1. Department of Emergency, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
  • Received:2020-06-28 Published:2020-08-18
  • Corresponding author: Erzhen Chen
  • About author:
    Corresponding author: Chen Erzhen, Email:
引用本文:

张继松, 王聿明, 郑彦俊, 祁星, 陈培莉, 史雯, 陈影, 杨之涛, 毛恩强, 陈尔真. NGAL对脓毒症/脓毒性休克患者预后的预测作用(已撤稿)[J/OL]. 中华卫生应急电子杂志, 2020, 06(04): 202-208.

Jisong Zhang, Yuming Wang, Yanjun Zheng, Xing Qi, Peili Chen, Wen Shi, Ying Chen, Zhitao Yang, Enqiang Mao, Erzhen Chen. Predictive effect of neutrophil gelatinase-associated apolipoprotein (NGAL) on prognosis in patients with sepsis/septic shock[J/OL]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2020, 06(04): 202-208.

目的

探究中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对脓毒症和脓毒性休克患者预后的预测作用。

方法

采用回顾性病例对照研究分析上海交通大学医学院附属瑞金医院急诊科2017年1月31日至2019年1月31日收治且明确诊断为脓毒症/脓毒性休克的84例患者,其中男性53例,女性31例;年龄18~80岁,平均(56.5±17.8)岁。根据患者的预后分为生生存组(n=62)和死亡组(n=22)。在患者入院第1天、第3天和第7天检测血浆NGAL水平,比较两组患者临床资料、实验室检查指标水平的差异,筛选出差异有统计学意义的观察指标对比,并采用pearson相关性分析比较NGAL与其他预后指标的相关性。再通过受试者工作特征曲线(ROC)曲线判断NGAL对脓毒症/脓毒性休克患者发生院内死亡和是否需行连续肾脏替代疗法(CRRT)治疗的预测价值。

结果

死亡组患者NGAL浓度在第1天[(2 188.4±2 280.8)ng/mL比(538.2±777.4)ng/mL]、第3天[(2 045.5±2 388.8)ng/mL比(553.8±836.4)ng/mL]和第7天[(1 512.4±1 840.9)ng/mL比(192.3±410.2)ng/mL]均明显高于生存组患者,差异均有统计学意义(P<0.05)。NGAL水平与序贯器官衰竭评分(Sequential Organ Failure Assessment, SOFA)(r=0.4601)、急性生理与慢性健康评分(APACHE Ⅱ)(r=0.37)、乳酸(r=0.41)和肌酐(r=0.48)都呈正相关性(P均<0.05)。第7天时NGAL水平对预后的预测价值[曲线下面积(AUROC)=0.85,95% CI:0.70~0.99]高于第1天(AUROC=0.71,95%CI:0.55~0.88)和第3天(AUROC=0.72,95%CI:0.55~0.88)。第3天时肌酐和NGAL对是否需行CRRT的预测价值优于第1天和第7天。入院第3天时NGAL浓度(AUROC=0.80,95%CI:0.64~0.97)与肌酐水平(AUROC=0.83,95%CI:0.68~0.97)相比,前者对患者是否需行CRRT的预测作用具有更好的特异性,但敏感度相对较低。

结论

对于脓毒症/脓毒性休克患者第7天时NGAL水平对预后具有很高的预测价值。与肌酐相比,NGAL对预测患者是否需行CRRT具有更高的特异性。

Objective

To investigate the predictive effect of neutrophil gelatinase-associated apolipoprotein (NGAL) on prognosis in patients with sepsis and septic shock.

Methods

In this study, 84 patients who were admitted to the emergency department of Ruijin Hospital from January 31, 2017 to January 31, 2019 and were clearly diagnosed with sepsis/septic shock were selected as the research subjects to conduct retrospective case analysis, including 53 males , 31 females, aged 18 to 80 years, with average age (56.5ubjects to conduct retrospective case analysis, including 53 males , 31 femaleere divided into the survival group (n=62) and the death group (n=22). The plasma NGAL levels were measured on the first day, the third day, and the seventh day of the patient’s admission, and the clinical results of the two groups were compared. Differences in data and laboratory examination index levels were screened out for comparison of observation indexes with statistical significance, and Pearson correlation analysis was used to compare the correlation between NGAL and other prognostic indexes. The receiver operating characteristic curve (ROC) curve was then used to determine the predictive value of NGAL for the occurrence of in-hospital death in patients with sepsis/septic shock and whether continuous renal replacement therapy (CRRT) was required.

Results

The NGAL concentration of patients in the death group was [(2 188.4±2 280.8) ng/mL vs.(538.2±777.4)ng/mL] on day 1 and [(2 045.5±2 388.8)ng/mL vs.(553.8±836.4)ng/mL] and the 7th day [(1 512.4±1 840.9)ng/mL vs.(192.3±410.2)ng/mL] were significantly higher than those in the survival group, and the differences were statistically significant (P<0.05). The patientr than those in thsequential organ failure assessment (SOFA) (r=0.4601), acute physiology and chronic health evaluation (APACHE Ⅱ) (r=0.37), lactic acid (r=0.41) and creatinine (r=0.48) had a strong positive correlation (P<0.05). The prognostic value of NGAL level on day 7 [area under the curve (AUROC)=0.85, 95% CI: 0.70-0.99] was higher than that on day 1 (AUROC=0.71, 95% CI: 0.55-0.88) and the third day (AUROC=0.72, 95%CI: 0.55-0.88). The predictive value of creatinine and NGAL on day 3 for CRRT was better than that on day 1 and day 7. Compared with the creatinine level (AUROC=0.83, 95%CI: 0.68-0.97) of NGAL concentration (AUROC=0.80, 95%CI: 0.64-0.97) on the third day of admission, the former had a predictive effect on whether patients need CRRT with better specificity, but relatively low sensitivity.

Conclusion

The NGAL concentration on day 7 has a high predictive value for prognosis. Compared with creatinine, NGAL is more specific in predicting whether patients need CRRT.

表1 入组患者流行病学资料统计[例(%)]
组别 例数 性别 年龄(岁,±s) BMI(±s) 疾病类型 APACHⅡ评分(分,±s) C-反应蛋白(mg/L, ±s) 降钙素原[ng/mL,M(QR)] 肌酐[μmol/L,M(QR)] 乳酸(mmol/L,±s)]
脓毒性休克 脓毒症
生存组 62 39(62.9) 23(37.1) 55.0±17.3 23.6±4.0 14(22.6%) 48(77.4%) 8.6±4.6 116.9±81.9 1.7(23.1) 74.0(115.5) 1.8±0.9
死亡组 22 14(63.6) 8(36.4) 60.5±18.5 24.5±4.2 10(45.5%) 12(54.5%) 12.0±4.6 119.2±76.5 3.0(24.6) 166.0(288.0) 2.7±2.6
t/χ2/U ? 0.004 ? 0.004 4.2 ? ? ? ? ?
P ? >0.05 >0.05 >0.05 <0.05 <0.05 >0.05 >0.05 <0.05 <0.05
组别 例数 感染来源 SOFA评分[分,M(QR)] 白细胞(×109/L,±s)
肠道 肺脏 泌尿系统 心脏 中枢神经 腹腔 皮肤/软组织 血流 不明部位
生存组 62 3(4.8) 26(41.9) 5(8.1) 1(1.6) 1(1.6) 20(32.3) 5(8.1) 0(0) 1(1.6) 4(3) 13.1±6.2
死亡组 22 2(9.1) 12(54.5) 2(9.1) 0(0) 0(0) 4(18.2) 0(0) 1(4.5) 1(4.5) 6(6) 8.1±4.7
t/χ2/U ? 0.04 1.0 0.02 0.6 0.6 1.0 3.1 2.7 0.5 ? ?
P ? >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05 <0.05
组别 例数 红细胞比容(%,±s) 血小板(×103/μL,±s) 肌钙蛋白I[μg/L,M(QR)] B型氨基端利钠肽原(IU/L, ±s) 行机械通气 行CRRT 使用血管活性药物 住院时间[d,M(QR)] ICU时间[d,M(QR)]
生存组 62 34.6±7.2 197.2±106.7 0.9±2.2 2 377.2±2 626.3 16(25.8) 8(12.9) 8(12.9) 29(28) 17(22)
死亡组 22 28.9±7.0 167.6±149.2 0.9±1.2 3 507.8±3 517.2 19(86.4) 7(31.8) 15(68.2) 13(22) 10(16)
t/χ2/U ? 22.1 4.0 25.0 ? ? ? ? ? ?
P ? <0.05 >0.05 >0.05 >0.05 <0.05 <0.05 <0.05 <0.05 >0.05
图1 两组脓毒症患者在入院第1、3、7天血浆NGAL比较
图2 84 例脓毒症患者的血浆NGAL与SOFA评分、APACHEⅡ评分、乳酸水平和肌酐水平的的相关性分析
图3 84 例患者NGAL对脓毒症/脓毒性休克患者发生院内死亡预测的ROC曲线
图4 84 例患者入院第1、3、7天NGAL与肌酐水平对脓毒症/脓毒性休克患者是否需要CRRT治疗预测的ROC曲线
1
Singer M, Deutschman CS, Seymour CW, et al.The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)[J].JAMA,2016,315(8):801-810.
2
Dellinger RP, Levy MM, Rhodes A, et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012[J].Intensive Care Med,2013,39(2):165-228.
3
马晓媛,田李星,梁华平.中西医结合诊治脓毒症的现状及思考[J/CD].中华卫生应急电子杂志,2015,1(6):13-17.
4
申庆民,李文雄,赵松,等.持续静脉-静脉血液滤过治疗对早期严重脓毒症患者细胞免疫功能的影响[J/CD].中华卫生应急电子杂志,2016,2(2):100-103.
5
于晶,谢晓华,张子敬.通腑泻热方治疗脓毒症的临床效果[J/CD].中华卫生应急电子杂志,2015,1(5):41-44.
6
冯凯,郑燕华,杨鹤鸣,等.SAA与脓毒症进程的相关性及其生物学意义[J/CD].中华卫生应急电子杂志,2018,4(5):290-297.
7
沈文明,岳茂兴,李瑛,等.动态监测创伤脓毒症患者血浆中高迁移率族蛋白B1含量的意义[J/CD].中华卫生应急电子杂志2015,1(6):28-30.
8
郑燕华,吴莹莹,冯凯,等.白介素-10家族成员IL-10、IL-22与脓毒症的关系[J/CD].中华卫生应急电子杂志,2018,4(4):243.
9
孙志林,刘大东,王旭,等.血浆microRNA-130 a联合APACHE Ⅱ评分预测脓毒症伴血小板减少患者死亡的巢式病例对照[J/CD].中华卫生应急电子杂志,2019,5(6):325-329.
10
Vanlaere I, Libert C.Matrix metalloproteinases as drug targets in infections caused by gram-negative bacteria and in septic shock[J].Clin Microbiol Rev,2009,22(2):224-239.
11
Haase M, Devarajan P, Haase-Fielitz A,et al.The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies[J].J Am Coll Cardiol,2011,57(17):1752-1761.
12
Cohen J, Vincent JL, Adhikari NK,et al.Sepsis: a roadmap for future research[J].Lancet Infect Dis,2015,15(5):581-614.
13
Rittirsch D, Flierl MA, Ward PA.Harmful molecular mechanisms in sepsis[J].Nat Rev Immunol,2008,8(10):776-787.
14
于中锴,张宗旺,管向东.脓毒症的研究进展[J/CD].中华卫生应急电子杂志,2019,5(2):59-62.
15
Lelubre C, Anselin S, Zouaoui Boudjeltia K,et al.Interpretation of C-reactive protein concentrations in critically ill patients[J].Biomed Res Int,2013,(2013):124021.
16
van Engelen TSR, Wiersinga WJ, Scicluna BP,et al.Biomarkers in Sepsis[J].Crit Care Clin,2018,34(1):139-152.
17
Mikkelsen ME, Miltiades AN, Gaieski DF,et al.Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock[J]. Crit Care Med,2009,37(5):1670-1677.
18
Chang W, Zhu S, Pan C,et al.Predictive utilities of neutrophil gelatinase-associated lipocalin (NGAL) in severe sepsis[J].Clin Chim Acta,2018,(481):200-206.
19
Grützner F, Rens W, Tsend-Ayush E,et al.In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes[J].Nature,2004,432(7019):913-917.
20
Haase M, Bellomo R, Devarajan P,et al.Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis[J].Am J Kidney Dis,2009,54(6):1012-1024.
21
Bagshaw SM, Bennett M, Devarajan P,et al.Urine biochemistry in septic and non-septic acute kidney injury: a prospective observational study[J].J Crit Care,2013,28(4):371-378.
22
Schmidt-Ott KM, Mori K, Li JY,et al.Dual action of neutrophil gelatinase-associated lipocalin[J].J Am Soc Nephrol,2007,18(2):407-413.
23
Mårtensson J, Bell M, Xu S,et al.Association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with sepsis and acute kidney dysfunction[J].Biomarkers,2013,18(4):349-356.
24
Wang M, Zhang Q, Zhao X,et al.Diagnostic and prognostic value of neutrophil gelatinase-associated lipocalin,matrix metalloproteinase-9,and tissue inhibitor of matrix metalloproteinases-1 for sepsis in the Emergency Department: an observational study[J].Crit Care,2014,18(6):634.
25
Smertka M, Wroblewska J, Suchojad A,et al.Serum and urinary NGAL in septic newborns[J].Biomed Res Int,2014,(2014):717318.
26
Kim H, Hur M, Lee S,et al.Proenkephalin,neutrophil gelatinase-associated lipocalin,and estimated glomerular filtration rates in patients with sepsis[J].Ann Lab Med,2017,37(5):388-397.
27
Wang B, Chen G, Zhang J,et al.Increased neutrophil gelatinase-associated lipocalin is associated with mortality and multiple organ dysfunction syndrome in severe sepsis and septic shock[J].Shock,2015,44(3):234-238.
28
Macdonald SPJ, Bosio E, Neil C,et al.Resistin and NGAL are associated with inflammatory response,endothelial activation and clinical outcomes in sepsis[J].Inflamm Res,2017,66(7):611-619.
29
Shapiro NI, Trzeciak S, Hollander JE,et al.The diagnostic accuracy of plasma neutrophil gelatinase-associated lipocalin in the prediction of acute kidney injury in emergency department patients with suspected sepsis[J].Ann Emerg Med,2010,56(1):52-59.e1.
[1] 许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[2] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[3] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[4] 屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.
[5] 李伟, 宋子健, 赖衍成, 周睿, 吴涵, 邓龙昕, 陈锐. 人工智能应用于前列腺癌患者预后预测的研究现状及展望[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 541-546.
[6] 陈樽, 王平, 金华, 周美玲, 李青青, 黄永刚. 肌肉减少症预测结直肠癌术后切口疝发生的应用研究[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(06): 639-644.
[7] 关小玲, 周文营, 陈洪平. PTAAR在乙肝相关慢加急性肝衰竭患者短期预后中的预测价值[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 841-845.
[8] 张润锦, 阳盼, 林燕斯, 刘尊龙, 刘建平, 金小岩. EB病毒相关胆管癌伴多发转移一例及国内文献复习[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 865-869.
[9] 陈晓鹏, 王佳妮, 练庆海, 杨九妹. 肝细胞癌VOPP1表达及其与预后的关系[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 876-882.
[10] 刘郁, 段绍斌, 丁志翔, 史志涛. miR-34a-5p 在结肠癌患者的表达及其与临床特征及预后的相关性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 485-490.
[11] 陈倩倩, 袁晨, 刘基, 尹婷婷. 多层螺旋CT 参数、癌胚抗原、错配修复基因及病理指标对结直肠癌预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 507-511.
[12] 曾明芬, 王艳. 急性胰腺炎合并脂肪肝患者CT 与彩色多普勒超声诊断参数与其病情和预后的关联性研究[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 531-535.
[13] 沈炎, 张俊峰, 唐春芳. 预后营养指数结合血清降钙素原、胱抑素C及视黄醇结合蛋白对急性胰腺炎并发急性肾损伤的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 536-540.
[14] 王景明, 王磊, 许小多, 邢文强, 张兆岩, 黄伟敏. 腰椎椎旁肌的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 846-852.
[15] 郭曌蓉, 王歆光, 刘毅强, 何英剑, 王立泽, 杨飏, 汪星, 曹威, 谷重山, 范铁, 李金锋, 范照青. 不同亚型乳腺叶状肿瘤的临床病理特征及预后危险因素分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(06): 524-532.
阅读次数
全文


摘要