The value of urine Soluble Triggering Receptor expressed on Myloid cell-1 in early diagnosis of Sepsis associated Acute Kidney Injury

Abstract

Objective: To assess the value of urine soluble triggering receptor expressed on myeloid cells-1(sTREM-1) in early diagnosis and prognosis of sepsis associated acute kidney injury (AKI). Methods: This was a case-control study. A total of 62 patients with sepsis during November 2016 to June 2017 were collected, who were divided into non-AKI sepsis (n= 49) and AKI sepsis (n=13) groups according to the serum creatinine (SCr) or urine output, sepsis with shock (n=22) and sepsis without shock (n=40) groups according to the presence of shock, survival (n=47) and death (n=15) groups according to the mortality. Twenty healthy children were recruited in control group, whose urine sTREM-1 were used as reference value. Urine and blood specimens were detected on admission (within 12 h), at 24 h and 48 h after admission. Student's t-test and Mann-Whitney U test were used for statistical analysis. Results: On admission, the level of urine sTREM-1 were significantly higher in sepsis patients than in healthy controls (96.8 (71.3, 105.8) vs. 68.6 (60.6, 71.1)ng/L, Z=4.708, P<0.05). Comparing of sTREM-1 in different groups showed that the levels were higher in AKI sepsis patients than in the non-AKI ones ((106±5) vs. (86±18) ng/L, t=6.670, P<0.05), higher in the sepsis with shock group than in sepsis without shock group ((98±11) vs. (86± 20) ng/L, t=3.059, P<0.05), and also higher in death group than in survival group ((101±12) vs. (87±18) ng/L, t=3.615, P<0.05). The area under the receiver operating characteristic (AUROC) of urine sTREM-1 in predicting sepsis associated AKI was 0.814 (95%CI: 0.708-0.920), which was higher than that in predicting shock, increased serum creatinine, hyperlipidemia or hyperbilirubinemia (0.530, 0.425, 0.429 and 0.443, respectively). The optimal sTREM-1 cut-off point for predicting sepsis associated kidney injury was 96.5 ng/L, with specificity and sensitivity of 100% and 57.1%. The odds ratio(OR) of urine sTREM-1 was 0.879 with a significance of 0.005 after adjusting shock, prognosis, serum creatinine, lactate and total bilirubin level, indicating that the urine sTREM-1 was an independent risk factor of sepsis associated AKI. Conclusion: Urine sTREM-1 can be used as an early diagnostic biomarker for sepsis associated AKI, with advantage of noninvasiveness and convenience. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-DDD-17010743. 目的： 探讨尿可溶性髓样细胞触发受体1(sTREM-1）在脓毒症儿童急性肾损伤（AKI ）早期诊断、病情及预后评估中的价值。 方法： 病例对照研究。纳入2016年11月至2017年6月在重庆医科大学附属儿童医院重症监护室（PICU）确诊为脓毒症的儿童62例，根据其血清肌酐值（Scr）或尿量分为脓毒症AKI组13例、脓毒症非AKI组49例；根据有无休克分为脓毒性休克组22例、脓毒症非休克组40例；根据预后分为死亡组15例、存活组47例，同时选择健康儿童20例作为正常对照组，其样本检测结果将作为本次研究中尿sTREM-1的基线值。检测各组入重症监护室当日（12 h内）、24 h、48 h尿sTREM-1和Scr水平。组间比较主要采用t检验和两独立样本非参数检验（Mann-Whitney U检验）。 结果： （1）入重症监护室当日，脓毒症组尿sTREM-1为96.8(71.3，105.8) ng/L，明显高于正常对照组68.6(60.6, 71.1) ng/L（Z=4.708,P<0.05）；脓毒症AKI组尿sTREM-1(106±5）ng/L，明显高于脓毒症非AKI组（86±18）ng/L （t=6.670, P<0.05）；（2）脓毒性休克组、脓毒症非休克组的尿sTREM-1水平分别为（98±11）、（86±20）ng/L，两组间比较差异有统计学意义（t=3.059,P<0.05）；（3）死亡组、存活组的尿sTREM-1水平为（101±12）、（87±18) ng/L，两组间差异有统计学意义（t=3.615, P<0.05）；（4）尿sTREM-1对诊断脓毒症相关性AKI的ROC曲线下面积是0.814 （95%CI：0.708~0.920 ），高于休克、Scr、高乳酸血症及高胆红素血症的曲线下面积（分别为0.530、0.425、0.429、0.443 ）；以sTREM-1=96.5 ng/L为临界值时，敏感度和特异度分别为100%、57.1%；（5）将脓毒症患儿是否存在休克、预后、Scr、血乳酸水平、总胆红素水平及尿sTREM-1水平纳入Logistic回归分析，结果显示，尿sTREM-1为脓毒症患儿发生AKI的独立危险因素（OR=0.879 ，P=0.005 ，95%CI：0.803~0.962 ）。 结论： 尿sTREM-1可以作为儿童脓毒症相关性急性肾损伤早期诊断的生物标志物，并优于传统的肾功能标志物如血清肌酐。使用尿液作为检测标本，无创、简便易行。临床试验注册：中国临床试验注册中心，ChiCTR-DDD-17010743。.