尿中性粒细胞明胶酶相关脂质运载蛋白测定对危重症患儿急性肾损伤的早期诊断意义

The significance of urine neutrophil gelatinase-associated lipocalin as an early diagnostic marker in critical ill children with acute kidney injury

目的 评估尿中性粒细胞明胶酶相关脂质运载蛋白（urine neutrophil gelatinase-associated lipocalin,uNGAL）对PICU患儿急性肾损伤的早期诊断价值.方法 对象是上海交通大学附属儿童医院2013年4月至6月期间PICU收治的80例危重症患儿.入PICU后连续观察72 h,根据急性肾损伤（acute kidney injury,AKI） pRIFLE标准将患儿分为AKI组15例和非AKI组65例.根据脓毒症的诊断标准将患儿分为脓毒症组31例和非脓毒症组49例,于入科6h内、24 h、48 h及72 h留取患儿尿液和血液测定uNGAL和血肌酐（serum creatinine,Scr）.比较AKI组与非AKI组、脓毒症未合并AKI组与非脓毒症非AKI组、脓毒症合并AKI组与脓毒症未合并AKI组间uNGAL水平的差异,以及AKI组Scr和uNGAL之间的相关度,绘制ROC曲线评价48 h uNGAL和Scr对危重症患儿AKI诊断的敏感性和特异性.结果 80例患儿中有13例进展为AKI.（1）AKI组6h内、24 h、48 h、72 h uNGAL[M（QR）,ng/ml]水平分别为863.00（696.00）、700.50（580.00）、365.50（285.00）、289.50（319.30）,明显高于非AKI组[20.00（106.00）、20.00 （85.30）、20.00（101.00）、20.00（36.00）] （P ＜0.01）.（2）新发展AKI组患儿uNGAL值各时间点均明显高于非AKI组,两组48 h Scr水平间差异有统计学意义.（3）脓毒症未合并AKI组uNGAL水平病初时升高,48 h后逐渐降至正常,与非脓毒症非AKI组比较差异无统计学意义.（4）脓毒症合并AKI组uNGAL水平持续明显升高,与脓毒症未合并AKI组比较差异有统计学意义（P＜0.01）.（5）48 h uNGAL和Scr的ROC曲线下面积分别为0.902（95％ CI：0.801 ～1.004）和0.874（95％ CI：0.768 ～0.981）.结论 uNGAL在儿童危重症合并AKI时较Scr提前24 ～ 48 h升高,反映疾病的严重程度,可以作为PICU患儿AKI的早期诊断标志物.

Objective To evaluate the value of urine neutrophil gelatinase-associated lipocalin （uNGAL） to early diagnose acute kidney injury（AKI） of critically ill children in PICU.Methods Eighty critically ill children at PICU of Children＆#39;s Hospital Affiliated to Shanghai Jiaotong University were enrolled in this study from April to June 2013.They were continuously observed for 72 hours.According to pediatric RIFLE criteria for diagnosis of AKI,patients were divided into AKI group （15 cases） or non-AKI group （65 cases）.Additionally,according to sepsis diagnostic criteria,patients were divided into sepsis group （31 cases） or non-sepsis group （49 cases）.The levels of serum creatinine and uNGAL were measured within 6th hour,24th hour,48th hour,72th hour after admitted to PICU.The differences of uNGAL levels between AKI and non-AKI groups,sepsis without AKI and non-sepsis non-AKI groups,sepsis merged AKI and sepsis without AKI groups were analysed.The sensitivity and specificity of uNGAL and serum creatinine for diagnosis of AKI at 48th hour were evaluated by ROC curve.Results Thirteen cases of eighty children developed to AKI after admitted to PICU.（1）The uNGAL levels [M（QR）,ng/ml] in AKI group within 6th hour,at 24th hour,48th hour,72th hour were 863.00 （696.00）,700.50 （580.00）,365.50 （285.00）,289.50 （319.30）,respectively,which were significantly higher than those in non-AKI group [20.00 （106.00）,20.00 （85.30）,20.00（101.00）,20.00（36.00）] （P 〈0.01）.（2）The uNGAL levels in new developed group were much higher than those in non-AKI group at each time point.The comparision of serum creatinine at 48th hour was statistic difference.（3）The uNGAL levels rised at early stage in sepsis without AKI group and down to normal gradually after 48th hour.（4）The uNGAL levels continued increasing in sepsis merged AKI group,and had significant differences comparing with sepsis without AKI group（P 〈 0.01）.（5） The areas under ROC curve of uNGAL and serum creatinine at 48th hour were 0.902（95% CI：0.801 ～ 1.004） and 0.801 （95% CI：0.768 ～ 0.981）,respectively.Conclusion The level of uNGAL has earlier increase for 24 to 48 hours than that of serum creatinine in critically ill children,and it can also reflect the severity of AKI.Therefore it can be used as an early diagnostic biomarker for AKI in PICU.