尿α1抗胰蛋白酶预测儿童原发性肾病综合征激素治疗的疗效  

Detection of urinary α1- antitrypsin for predicting response to glucocorticoid therapy in childrenwith primary nephrotic syndrome

作　　者：王荧荧[1] 丁桂霞[1] 袁杨刚[1] 鲍华英[1] 陈颖[1] 赵非[1] 韩媛[1] 张爱华[1] 黄松明[1] 

机构地区：[1]南京医科大学附属南京儿童医院肾脏科,210008

出　　处：《中华肾脏病杂志》2012年第11期857-862,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30971376）;江苏省自然科学基金（BK2009046）

摘　　要：目的检测儿童原发性肾病综合征（PNS）激素使用前尿α1抗胰蛋白酶（AAT）水平，探讨其能否作为儿童PNS激素治疗敏感性的预测指标。方法43例PNS初治儿童，留取其激素使用前的晨起中段尿，应用ELISA法检测尿液中AAT的浓度，并经同份尿肌酐浓度校正。根据糖皮质激素治疗4周后的反应分为激素敏感（SSNS）组和激素耐药（SRNS）组，15例健康的体检儿童作为对照组（NC）。分析各组间数据差异及评价AAT的预测效能。结果对照组尿AAT检测阴性，SSNS组及SRNS组间尿AAT水平差异无统计学意义[（30．4±4．5）mg／L比（31．8±4．6）mg／L，t=-1．0，P=0．33]；而经尿肌酐校正后的尿AAT（尿AAT／Cr）在SRNS组显著高于SSNS组[0．049（0．028-0．073）比0．028（0．022-0．036），Z=2．4，P=0．021。激素使用前SRNS组实验室指标中血小板计数、血白细胞计数、血清球蛋白水平、尿白细胞计数、尿红细胞计数、尿IgG水平及尿d1微球蛋白水平显著高于SSNS组（P〈0．05）；其中尿AAT／Cr（OR=6．81×10^28，P=0．005）、血清球蛋白（OR=1．69，P=0．01）及尿d1微球蛋白（OR=1．05，P=0．009）进人多因素Logistic回归模型，作为预测SRNS的独立因素。据两组尿AAT／Cr作ROC，曲线下面积（AUC）为0．72，当尿AAT／Cr截取值为0．035时，预测效能最高，其灵敏度为68％，特异度为75％（Youden指数为0．43）。据回归模型中尿AAT／Cr、血清球蛋白及尿α1微球蛋白联合作ROC，其AUC为0．94，灵敏度为95％，特异度为83％（Youden指数为0．78）。尿AAT／Cr在不同病理类型间差异无统计学意义。结论SSNS组及SRNS组间尿AAT水平差异无统计学意义，而SRNS患儿尿AAT／Cr显著高于SSNS患儿，其可作为PNS激素疗效预测指标；尿AAT／Cr联合血清球蛋白和尿α1微球蛋白对SRNS有更好的预测效能。Objective To detect the α1- antitrypsin （AAT） concentration in urine samples of children with primary nephrotie syndrome （PNS） before initiation of glucocorticoid treatment, in order tO verify whether it could predict the response to glucocorticoid- based therapy. Methods Forty- three children diagnosed as PNS initially were chosen as subjects, namely steroid-sensitive nephrotic syndrome （SSNS） and steroid- resistant nephrotic syndrome （SRNS） depending on reaction to glucocorticoid therapy four weeks later, and 15 healthy children serving as normal control. The mid stream of the first morning urine samples were collected from children before taking glucocorticoid. ELISA kit was used to quantify the urinary AAT concentration which was revised by urine creatinine further. The data of urine AAT/Cr were expressed as median with interquartile range. Data analysis was performed using the SPSS 17.0. ResultsAAT was absent in urine samples of normal healthy children, and there were no statistic differences of the AAT concentrations in urine between children with SSNS and SRNS [（30.4±4.5） mg/L vs （31.8±4.6） rag/L, t=-1.0, P=0.33]. The level of urine AAT/Cr in children with SRNS was higher than that in children with SSNS [0.049（0.028-0.073） vs 0.028（0.022-0.036）, Z=2.4, P=0.02]. Among the laboratory parameters of the two subgroups before taking glucocortiod, the levels of platelet, blood white cell count, serum globulin, urine white cell count, urine red cell count, urine IgG and urine α1-microglobulin were significantly different （P〈 0.05）. Three parameters that included urine AAT/Cr （OR=6.81× 10^28, P=0.005）, serum globulin （OR=1.69, P=0.01） and urine α1- microglobulin （0R=1.05, P=0.009） further entered the logistic regression model to predict the SRNS independently. The ROC curve based on the level of the urine AAT/Cr was constructed, and the area under the curve （AUC） was 0.72. When the cutoff value of urine AAT/Cr was 0.035, the sensitivity and specificity of

关 键 词：Α1抗胰蛋白酶 肾病综合征 糖皮质激素类 激素耐药 

分 类 号：R726.9[医药卫生—儿科]