目的探讨高迁移率族蛋白1(HMGB1)对脓毒症及相关急性肾损伤(AKI)的诊断和预后的评估价值。方法选取2014年10月—2015年3月武汉大学人民医院确诊的脓毒症患者40例,根据病情严重程度分为普通脓毒症组12例和严重脓毒症组28例。将严重脓毒症组患者根据28 d病情转归情况分为恶化亚组13例和好转亚组15例;又根据是否并发AKI分为严重脓毒症AKI亚组18例,严重脓毒症非AKI亚组10例,同样根据28 d病情转归情况将18例严重脓毒症AKI患者进一步分为恶化亚组11例和好转亚组7例。另选取同期健康志愿者5例为对照组。收集患者入组24 h内的临床资料并采集血、尿标本。酶联免疫吸附法(ELISA)检测血及尿HMGB1水平。采用SPSS 17.0软件进行统计学分析。结果 (1)40例脓毒症患者的血及尿HMGB1水平均高于对照组(P〈0.01)。严重脓毒症组血HMGB1水平高于普通脓毒症组,差异有统计学意义(P=0.027)。当以血HMGB1水平为1 225.1 ng/L作为鉴别严重脓毒症与普通脓毒症截断点时,灵敏度与特异度分别为67.9%和75.0%,ROC曲线下面积为0.74〔95%CI(0.56,0.91),P=0.020〕。(2)Pearson相关分析结果显示,血HMGB1水平与尿HMGB1水平、白细胞计数(WBC)及降钙素原(PCT)呈正相关(r=0.472、0.597、0.473,P=0.011、0.001、0.011),尿HMGB1水平与估算肾小球滤过率呈正相关(r=0.480,P=0.010),与急性生理与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、血肌酐水平呈负相关(r值分别为-0.506和-0.397,P值分别为0.006和0.038)。多元线性回归分析结果显示,尿HMGB1水平、WBC、PCT是严重脓毒症组血HMGB1水平的影响因素,清蛋白与APACHEⅡ评分是尿HMGB1水平的影响因素(P〈0.05)。(3)当以尿HMGB1水平为961.0 ng/L作为截断点时,鉴别严重脓毒症恶化与好转的灵敏度与特异度分别为73.3%和92.3%,ROC曲线下面积为0.84〔95%CI(0.69,0.99),P=0.002〕。(4
Objective To investigate the diagnostic and prognostic value of high mobility group box 1( HMGB1) for sepsis and sepsis- induced acute kidney injury( AKI). Methods We enrolled 40 patients who were definitely diagnosed with sepsis in Renmin Hospital of Wuhan University from October 2014 to March 2015. According to the severity degree of disease,12 patients were assigned into normal sepsis group, and 28 patients were assigned into severe sepsis group. According to 28 d outcome,the patients of severe sepsis group were divided into worsening subgroup( n = 13) and improving subgroup( n = 15);according to whether AKI occurred,the patients were further divided into severe sepsis AKI subgroup( n = 18) and severe sepsis non-AKI subgroup( n = 10); according to 28 d outcome, the patients in severe sepsis AKI group were further divided into worsening subgroup( n = 11) and improving subgroup( n = 7). We also enrolled 5 healthy volunteers as control group. Within24 hours after enrollment,clinical data were collected and blood and urine samples were taken. The levels of plasma and urine HMGB1 levels were detected using ELISA method. SPSS 17. 0 software was used to conduct statistic analysis. Results( 1)Sepsis group was higher than control group in plasma and urine HMGB1 level( P〈0. 01). Severe sepsis group was higher than normal sepsis group in plasma HMGB1 level( P = 0. 027). When plasma HMGB1 level was 1 225. 1 ng / L,which was taken as the cut- off point of the identification of severe sepsis and normal sepsis,the sensitivity and specificity were 67. 9% and 75. 0%respectively,and the AUC was 0. 74 〔95% CI( 0. 56,0. 91),P = 0. 020 〕.( 2) Pearson correlation analysis showed that plasma HMGB1 level was positively correlated with urine HMGB1 level, WBC and PCT( r = 0. 472,0. 597,0. 473; P =0. 011,0. 001,0. 011); urine HMGB1 level was positively correlated with e GFR( r = 0. 480,P = 0. 010),and was negatively correlated with APACHE Ⅱ score and serum creatinine le