氯离子清除试验在Gitelman综合征鉴别诊断中的应用  

Value of Chloride Clearance Test in Differential Diagnosis of Gitelman Syndrome

作　　者：彭晓艳[1] 蒋兰萍[1] 袁涛[2] 乐偲[1] 郑可[1] 王鸥[2] 李乃适[2] 李伟[2] 童安莉[2] 邢小平[2] 李雪梅[1] 李学旺[1] 陈丽萌[1] PENG Xiao-yan JIANG Lan-ping YUAN Tao YUE Cai ZHENG Ke WANG Ou LI Nai-shi LI Wei TONG An-li XING Xiao-ping LI Xue-mei LI Xue-wang CHEN Li-meng(Department of Nephrology State Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院肾内科,北京100730 [2]中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生和计划生育委员会重点实验室,北京100730

出　　处：《中国医学科学院学报》2016年第3期275-282,共8页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(81470937;81170674);首都特色临床研究~~

摘　　要：目的评估氯离子清除试验在Gitelman综合征(GS)鉴别诊断中的应用价值。方法以临床低钾、碱中毒、疑诊为GS的患者为研究对象,提取外周血DNA进行SLC12A3基因筛查作为金标准。按照标准操作流程进行氢氯噻嗪试验和速尿试验,测定患者基线和用药后3 h内氯离子排泄分数改变量的最大值(ΔFECl),评价对氢氯噻嗪和速尿的反应性,并与健康受试者比较,绘制受试者工作特征(ROC)曲线确定ΔFECl绝对值和相对值诊断GS的截点,计算氯离子清除试验诊断GS的灵敏度和特异度。结果 27例患者和20例健康受试者进行了氢氯噻嗪试验。以SLC12A3基因检测为诊断金标准,23例患者被诊断为GS。以ΔFECl绝对值和相对值诊断GS的ROC曲线下面积分别为0.987(95%CI:0.963~1.000,P〈0.001)和0.984(95%CI:0.950~1.000,P〈0.001)。选择适当的截点,灵敏度和特异度均达到95%以上。8例患者同时完成了氢氯噻嗪试验和速尿试验,其中5例患者对氢氯噻嗪无反应(ΔFECl绝对值≤2.86%或相对值≤223%),对速尿反应敏感,同时存在SLC12A3基因突变,确诊为GS;3例患者对氢氯噻嗪反应敏感,而使用速尿后FECl改变不明显,基因测序除外GS,考虑Bartter综合征可能性大。结论临床上综合应用氢氯噻嗪试验和速尿试验观察氯离子排泄分数的变化能有效鉴别GS和BS患者。Objective To investigate the value of chloride clearance test in differential diagnosis of Gitelman syndrome (GS) . Methods For patients with hypokalemic metabolic alkalosis and highly suspected GS, clinical data were documented and SLC12A3 gene screening was performed as gold standard to diagnose GS. Hydrochlorothiazide (HCT) test and furosemide (FUR) test were performed according to the standard process.Baseline and maximal increasement of chloride excretion fraction (FEC1, the net and relative increase measured as ~FEC1) were compared between patients and controls to evaluated the reaction to the corresponding diuretics. Re- ceiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of HCT test in GS diagnosis. Results Totally 27 patients and 20 health controls received HCT test. Among those patients, 23 were diagnosed with GS genetically. When using the net and relative AFEC1 to diagnose GS, the areas under the ROC curve were 0. 987 (95% CI: 0. 963, 1.000, P 〈 0. 001 ) and 0. 984 (95% CI: 0. 950 ~ 1. 000, P 〈 0. 001 ), re- spectively. When a reasonable cutoff value for aFEC1 was selected, the sensitivity and specificity were both higher than 95%. Eight patients received both HCT test and FUR test. Five of them showed decreased reaction to HCT (net aFECI≤2. 86% or relative aFECl≤223% ), while normal reaction to FUR. SLC12A3 mutations confirmed their GS. Three patients with blunt reaction to FUR showed normal reaction to HCT, finally they were diagnosed as BS clinically because no SLC12A3 gene mutation was detected. Conclusion Comprehensive application of HCT test and FUR test to evaluate the diuretic reaction can effectively differentiate GS and BS.

关 键 词：GITELMAN综合征 氯离子清除试验 诊断试验 

分 类 号：R692.6[医药卫生—泌尿科学]