Diagnostic and prognostic value of urinary neutrophil gelatinase-associated lipocalin in septic patients with acute kidney injury
-
摘要: 目的: 观察并探讨尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)在脓毒症患者急性肾损伤(AKI)早期诊断、诊断分层、预后中的临床价值。方法: 纳入2014-07-2016-06我院急诊科收治的、符合脓毒症标准的患者240例。按照AKIN定义分为脓毒症AKI组(124例)和脓毒症非AKI组(116例);此外,选取同期在我院体检的健康对照组30例。分别收集2组患者入急诊0、6、12、24、48 h尿液标本进行NGAL检测,并同时收集2组患者0、24、48 h血肌酐以及入急诊时的血降钙素(PCT)、乳酸、C反应蛋白(CRP)、SOFA评分等临床指标。结果: 与健康对照组对比,脓毒症AKI组和脓毒症非AKI组患者uNGAL、乳酸、PCT等指标均升高;相对脓毒症非AKI组,脓毒症AKI组患者uNGAL、血肌酐、血乳酸、PCT水平、SOFA评分更高(P<0.05),且住院天数延长(P<0.05)。脓毒症AKI组患者的uNGAL水平随AKI 1期、2期、3期分期依次递增、且随病程时间变化逐渐上升(P<0.05);脓毒症非AKI组患者入院48 h后新增22例AKI患者(19.1%);与脓毒症非AKI患者相比,血肌酐水平从24 h后开始升高,48 h升高更显著;而uNGAL水平则从入急诊室时已明显升高(P<0.05);uNGAL诊断AKI曲线下面积为0.838(95%CI:0.732~0.947),最佳临界值179 μmol/L,敏感度和特异度为0.727和0.713。使用uNGAL预测脓毒症患者28 d死亡,以uNGAL 48 h ROC曲线下面积最大为0.818(95%CI:0.758~0.877)、最佳截断值为375 ng/ml,敏感度和特异度分别为0.747和 0.746。结论: uNGAL可能对脓毒症患者AKI具有一定的诊断、分期、预测结局的价值。Abstract: Objective: To observe and investigate the clinical value of neutrophil gelatinase-associated lipocalin (NGAL) in urine in early diagnosis,diagnosis and prognosis of acute renal injury (AKI) in patients with sepsis. Method: Two hundred and forty patients with sepsis from July 2014 to June 2016 were treated in our hospital emergency department According to the definition of AKIN all patients were divided into septic AKI group (n=124) and septic non-AKI group (n=116);Urine samples were collected at 0,6,12,24 and 48 h after the entrance of the emergency department for NGAL detection.And we also recorded serum creatinine,calcitonin (PCT),lactic acid,c-reactive protein (CRP),SOFA score at the same time. Result: Compared with healthy control group,uNGAL,lactic acid,and PCT of patients in the experimental septic AKI group and experimental septic non-AKI group were elevated.The level of uNGAL、serum creatinine、blood lactic acid、PCT and SOFA score were higher in the experimental septic AKI group than those in septic non-AKI group (P<0.05),the levels of uNGAL in experimental septic AKI group increased according to the order of AKI 1,2 and 3,and gradually increased with the course of disease (P<0.05);In the experimental septic non-AKI group,22 patients with AKI (19.1%) were enrolled after 48 h of admission;and the serum creatinine levels increased obviuosly after 24 h compared with non-AKI patients with sepsis;The level of the uNGAL were significantly higher than those of the control group (P<0.05) when they enter Emergency room.The areas under the AKI curve was 0.838(95%CI:0.732~0.947).The optimal threshold was 179 μmol/L,and the sensitivity and specificity of the uNGAL were 0.727 and 0.713.When using uNGAL to predict sepsis in patients with 28-day mortality,the area under the curve of uNGAL 48 h ROC was 0.818 (95%CI:0.758~0.877),and the maximum cutoff was 375 ng/ml,and the sensitivity and specificity were 0.747 and 0.746.Conclusion: Urine NGAL may have clinical application value of a certain diagnosis,staging,predicting the clinical outcome in the sepsis patients with AKI.
-
Key words:
- sepsis /
- acute renal injury /
- urinary NGAL /
- early diagnosis /
- staging and prognosis /
-
[1] Seymour C W, Liu V X, Iwashyna T J, et al.Assessment of clinical criteria for sepsis:for the third international consensus definitions for sepsis and septic shock (Sepsis-3)[J].JAMA, 2016, 315 (8):762-774.
[2] Uchino S, Kellum J A, Bellomo R, et al.Acute renal failure in critically ill patients:A multinational, multicenter study[J].JAMA, 2005, 294 (7):813-818.
[3] Silvester W, Bellomo R, Cole L.Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia[J].Crit Care Med, 2001, 29 (10):1910-1915.
[4] Bagshaw S M, Laupland K B, Doig C J, et al.Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure:A population-based study[J].Crit Care, 2005, 9 (6):R700-R709.
[5] Bagshaw S M, Uchino S, Bellomo R, et al.Septic acute kidney injury in critically ill patients:Clinical characteristics and outcomes[J].Clin J Am Soc Nephrol, 2007, 2 (3):431-439.
[6] Bagshaw S M, George C, Bellomo R, et al.Early acute kidney injury and sepsis:A multicentre evalu-ation[J].Crit Care, 2008, 12 (2):R47-R47.
[7] Devarajan P.Neutrophil gelatinase-associated lipocalin:apromising biomarker for human acute kidney injury[J].Biomark Med, 2010, 4 (2):265-280.
[8] Cai L, Rubin J, Han W, et al.The origin of multiple molecu-lar forms in urine of HNL/NGAL[J].Clin J Am Soc Nephrol, 2010, 5 (12):2229-2235.
[9] Glassford N J, Schneider A G, Xu S, et al.The nature and discrimina-tory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury[J].Intensive Care Med, 2013, 39 (10):1714-1724.
[10] Martensson J, Xu S, Bell M, et al.Immunoassays distinguishing between HNL/NGAL released in urine from kidney epithelial cells and neutrophils[J].Clin Chim Acta, 2012, 413 (19-20):1661-1667.
[11] Mori K, Lee H T, Rapoport D, et al.Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury[J].J Clin Invest, 2005, 115 (3):610-621.
[12] Dellinger R P, Levy M M, 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.
[13] Bagshaw S M, Lapinsky S, Dial S, et al.Acute kidney injury in septic shock:clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy[J].Intensive Care Med, 2009, 35 (5):871-881.
[14] Gammelager H, Christiansen C F, Johansen M B, et al.Five-year risk of end-stage renal disease among intensive care patients surviving dialysis-requiring acute kidney injury:a nationwide cohort study[J].Crit Care, 2013, 17 (4):R145.
[15] Siew E D, Matheny M E, Ikizler T A, et al.Commonly used surrogates for baseline renal function affect the classification and prognosis of acute kidney injury[J].Kidney Int, 2010, 77 (6):536-542.
[16] Bagshaw S M, George C, Bellomo R.Early acute kidney injury and sepsis:a multicentre evaluation[J].Crit Care, 2008, 12 (2):R47-R47.
[17] 韩静, 邱俏檬, 吴斌, 等.脓毒症并发急性肾损伤患者临床特点及预后因素分析[J].中华危重症医学杂志:电子版, 2014, 7 (1):30-34.
[18] Haase M, Kellum J, Ronco C.Subclinical AKI——an emerging syndrome with important consequences[J].Nat Rev Nephrol, 2012, 8 (12):735-739.
[19] Devarajan P.Neutrophil gelatinase-associated lipocalin (NGAL):a new marker of kidney disease[J].Scand J Clin Lab Invest, 2008, 241:89-94.
[20] Bagshaw S W, Gibney R T.Conventional markers of kidney function[J].Crit Care Med, 2008, 36 (4 Suppl):S152-S158.
[21] Nickolas T L, O'Rourke M J, Yang J, et al.Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury[J].Ann Intern Med, 2008, 148 (11):810-819.
[22] Devarajan P.Neutrophil gelatinase-associated lipocalin-an emerging troponin for kidney injury[J].Nephrol Dial Transplant, 2008, 23 (12):3737-3743.
[23] Feldkamp T, Bienholz A, Kribben A.Urinary neutrophil gelatinase-associated lipocalin (NGAL) for the detection of acute kidney injury after orthotopic liver transplantation[J].Nephrol Dial Transplant, 2011, 26 (5):1456-1458.
[24] Patel M L, Sachan R, Shyam R, et al.Diagnostic accuracy of urinary neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury[J].Int J Nephrol Renovasc Dis, 2016, 9:161-169.
[25] Parikh C R, Coca S G, Thiessen-Philbrook H, et al.TRIBE-AKI Consortium Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery[J].J Am Soc Nephrol, 2011, 22 (9):1748-1757.
[26] Parikh C R, Devarajan P, Zappitelli M, et al.Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery[J].J Am Soc Nephrol, 2011, 22 (9):1737-1747.
[27] Krawczeski C D, Goldstein S L, Woo J G, et al.Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass[J].J Am Coll Cardiol, 2011, 58 (22):2301-2309.
[28] Yan L, Borregaard N, Kjeldsen L, et al.The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9and neutro-phil gelatinase-associated lipocalin (NGAL).Modulation of MMP-9activity by NGAL[J].J Biol Chem, 2001, 276 (40):37258-37265.
[29] Nickolas T L, Forster C, Sise M E, et al.NGAL (Lcn2) monomeric is associated with tubulointerstitial damage in chronic kidney disease[J].Kidney Int, 2012, 82 (6):718-722.
[30] Nga H S, Medeiros P, Menezes P, et l.Sepsis and AKI in clinical emergency room patients:the role of urinary NGAL[J].Biomed Res Int, 2015, 2015:413751.
[31] 张连东, 裴新军, 谭美春, 等.UNGAL在危重病患者急性肾损伤中的诊断意义[J].中国急救医学, 2016, 36 (8):692-695.
[32] 孟东亮, 邢海波, 茅尧生, 等.中性粒细胞明胶酶相关脂质运载蛋白对脓毒症继发急性肾损伤患者的早期预测价值[J].中华危重症医学杂志 (电子版), 2015, 8 (4):224-229.
[33] Hoste E A, Clermont G, Kersten A, et al.RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients:A cohort analysis[J].Crit Care, 2006, 10 (3):R73-R73.
计量
- 文章访问数: 121
- PDF下载数: 40
- 施引文献: 0