脓毒血症并发急性肾损伤早期诊断标志物的研究

Prediction of acute kidney injury complicated by sepsis with neutronphil gelatinase-associated lipocalin as an early marker

目的 探讨NGAL预测脓毒血症后AKI的准确性.方法 收集74例脓毒血症患者诊断后不同时间点的血、尿标本,对其中17例AKI患者,采用固相夹心酶联免疫吸附法检测尿NGAL水平,胶乳颗粒增强的免疫透射浊度法测定Cys C的值,肌氨酸氧化酶法测定Set水平.同期的57例非AKI患者作为研究的对照.观察两组患者毒血症诊断后尿NGAL和Scr的动态变化.运用ROC曲线评价尿NGAL诊断AKI的准确性.结果 Scr基线值为（59.38±16.72）μmoL/L,诊断AKI的中位时间为脓毒血症确诊后的24（12,48）h,Scr为（100.35±28.26）μmol/L.本组脓毒血症后发生AKI17例,发生率为23%（17/74）.脓毒血症AKI组患者2、4、6 h血清Cys C水平分别为（0.63±0.14）mg/L、（0.68±0.16）mg/L、（0.65±0.14）mg/L,与基线值（0.61±0.15）mg/L比较未见上升;8 h时,其血清Cys C值小幅升高为（0.85±0.22）mgs/L,但差异无统计学意义（t=1.63,P＞0.05）;12、18、24、36、48及72 h等各时间点的血清Cys C值呈逐渐升高的趋势,与基线值比较差异均有统计学意义（t=2.81、2.98、3.05、3.11、3.38、3.17,P＜0.01）.AKI组脓毒血症后2 h尿NGAL为（96.21 ±45.32）μg/L,显著高于基线值的（4.98±1.65）μg/L.随后,在2 h至48 h等各时间点,患者尿NGAL水平呈逐渐升高的趋势,与基线值比较差异均有统计学意义（t=2.74、2.83、2.91、3.04、3.15、3.22、3.31、3.45、3.57,P＜0.01）.AKI组脓毒血症后各时间点尿NGAL水平均显著高于同期的非AKI组,差异有统计学意义（t=2.69、2.73、2.84、2.96、3.02、3.13、3.29、3.43、3.54、3.22,P＜0.01）.用ROC曲线分析脓毒血症后2 h尿NGAL水平在AKI诊断中的准确性,得到ROC曲线下面积为0.935,95%的可信区间为0.683～0.971.当脓毒血症后2 h尿NGAL的cut-off值为50μg/L时,其在AKI诊断中的敏感度和特异度及准确性分别为94.4%、87.5%和96.8%.结论 脓毒血症后2 h尿NGAL水平可以准确地预测AKI的发生,其诊断AKI的时间早于Cys C和Scr.尿NGAL可作为脓毒血症后AKI的早期诊断标志物.

Objective To investigate the accuracy of NGAL in prediction of acute kidney injury （AKI） complicated by sepsis. Methods Blood and urine samples were collected at different time points in 74 sepsis patients, and 17 AKI patients were got from them.Cysteine Cys C levels were detected with Latex enhanced turbidimetric immunoassay （LETIA）. Urine NGAL and Scr levels were detected with solid-phase sandwich enzyme-linked immunosorbent assay and creatinine enzymatic assay respectively. At the same time, 57 non-AKI patients were set as controls. Dynamic changes of urine NGAL and Scr were observed in sepsis patients in test and control group. ROC curve was used to evaluate the performance of AKI diagnosis by urinary NGAL.Results The Scr base line was （59. 38 ±16. 72） μmol/L.The median time of diagnose of AKI was 24 （12, 48） h past-sepsis diagnosis, while the Scr was（100. 35± 28. 26） μmol/L. Of the group, 17 cases of sepsis were diagnosed with AKI, accounting for 23% （17/74） prevalence. In sepsis group, base line value[（0. 61 ± 0. 15） mg/L] of serum Cys C was not upregulated at 2, 4 and 6 h, which was （0. 63 ± 0. 14） mg/L, （0. 68 ± 0. 16） mg/L and （0.65±0. 14） mg/L respectively. As to 8 h [（0. 85 ± 0. 22） mg/L], a slight upregulation was found with no significant difference （t = 1.63, P ＞ 0. 05）.A trend of gradual increase of serum Cys C levels was found in sepsis AKI group at 12, 18, 24, 36, 48 and 72 h. A significant difference was found compared with base line （t = 2. 81, 2.98, 3.05, 3.11, 3. 38,3. 17,P ＜0.01）. NGAL level[（96.21 ±45.32） μg/L] was significantly higher than base line value [（4. 98 ± 1.65） μg/L]. Subsequently, in each time point from the 2 h to 48 h, a trend of gradual increase in urinary NGAL levels was showed. The differences were significant compared with the baseline values （t =2. 74,2. 83,2. 91,3.04,3.15,3.22,3. 31,3.45,3.57 ,P ＜0. 01）. Urinary NGAL levels of sepsis AKI group were significantly higher than those in non-AKI group at different time points with significant difference （t =2. 69,2. 73,2. 84,2. 96,3.02,3. 13,3.29,3.43,3.54,3.22,P ＜0. 01）. ROC curve was selected to analyze diagnostic performance of urinary NGAL levels in AKI patients 2 h post-sepsis. Area under ROC curve was obtained as 0. 935, 95% confidence interval was 0. 683-0. 971. When cut-off value of urinary NGAL for patients 2 h post-sepsis was 50 μg/L, the sensitivity, specificity and accuracy were 94. 4%, 87. 5% and 96. 8% in AKI diagnosis respectively. Conclusions The occurrence of AKi can be accurately predicted by urinary NGAL levels 2 h post-sepsis , and its AKI diagnosis time is earlier than that of Scr. Urine NGAL can be used as early marker of AKI complicated by sepsis.