尿醛固酮浓度在原发性醛固酮增多症中的筛查价值及质谱法和化学发光法检测的比较

Urinary Aldosterone Concentration:Its Value in Primary Aldosteronism Screening and Comparison of a LC-MS/MS Assay and a CLIA Assay for Its Determination

【目的】了解尿醛固酮浓度(UAC)对于原发性醛固酮增多症(原醛)的诊断价值;对比研究液相色谱串联质谱法(LC-MS/MS)和化学发光法(CLIA)检测UAC结果的一致性并建立各自的诊断切点。【方法】纳入2018年10月至2019年8月就诊的高血压查因患者133例,其中原醛患者55例(醛固酮瘤30例,特发性醛固酮增生25例),原发性高血压(EH)患者78例。采用CLIA法及LC-MS/MS法平行检测UAC并比较两种方法的相关性、一致性。构建UAC、尿醛固酮/肾素活性比值(UARR)诊断原醛的受试者工作特征(ROC)曲线。以尿钠≥130 mmol/24 h为界建立相对高尿钠组(n=51),比较不同钠盐摄入情况对于诊断价值的影响。【结果】①CLIA法与LC-MS/MS法检测的UAC结果呈正相关(r=0.69,P<0.01),Bland-Altman法分析提示两种方法所测UAC一致性欠佳。②UACCLIA及UACLC-MS/MS诊断原醛的价值均不及ARR。而UACCLIA及UACLC-MS/MS的诊断价值无统计学差异。UACCLIA的ROC曲线下面积(AUC)为0.739,切点为5.1μg/24 h。UACLC-MS/MS的AUC为0.659,切点为11.6μg/24 h。ARR的AUC为0.943,最佳切点为23.2 ng·dL^-1(/μg·L^-1·h^-1)。③UARR对于原醛的诊断价值较高,与ARR相当。UARRCLIA的AUC为0.924,诊断切点为1.75μg·24 h^-1/(μg·L^-1·h^-1)。UARRLC-MS/MS的AUC为0.906,诊断切点为4.63μg·24 h^-1/(μg·L^-1·h^-1)。④相对高尿钠亚组UACLC-MS/MS的AUC为0.708,切点为14.9μg/24 h。诊断价值较分组前并不能进一步提高。【结论】单一指标UAC诊断原醛的价值较低,但UARR诊断原醛的诊断价值显著提高,与ARR相当。UACLC-MS/MS、UACCLIA诊断切点分别为11.6μg/24 h、5.1μg/24 h,UARRLC-MS/MS、UARRCLIA的诊断切点分别为4.63μg·24h^-1(/μg·L^-1·h^-1)、1.75μg·24 h^-1(/μg·L^-1·h^-1)。另LC-MS/MS法与CLIA法检测UAC一致性欠佳,提示临床上使用不同检测方法需要采用不同参考值范围。

【Objective】To explore the clinical value of urinary aldosterone concentration(UAC)in primary aldoste⁃ronism(PA)screening and to evaluate the consistency of the two methods,liquid chromatography tandem mass spectrome⁃try(LC-MS/MS)and chemiluminescence immunosorbent assay(CLIA),for determining UAC.【Methods】Among the 133 patients with suspected PA enrolled from October 2018 to August 2019,55 were diagnosed with PA(30 with aldosteroneproducing adenoma and 25 with bilateral idiopathic hyperplasia)and 78 with essential hypertension(EH).Parallel deter⁃mination of UAC was done with LC-MS/MS and CLIA assays on all subjects,then we compared the two methods and evalu⁃ated their correlation and consistency.Reciever operating characteristic(ROC)analysis was applied to assess the diagnos⁃tic accuracies,area under the curve(AUC)and cutoff values of UAC,plasma aldosterone concentration(PAC),random aldosterone to renin ratio(ARR)and urine aldosterone to renin ratio(UARR).Furthermore,ROC analysis of high urine sodium subgroup(urine sodium≥130 mmol/24h)was performed to evaluate the impact of sodium intake on PA screening.【Results】①UACCLIA and UACLC-MS/MS were positively correlated(r=0.69,P<0.001).Bland-Altman analysis showed poor consistency between CLIA and LC-MS/MS.②The diagnostic efficiency of UAC and PAC in PA screening was equivalent(P>0.05),while ARR was more efficient than UAC and PAC(P<0.0001).AUC of UACCLIA,UACLC-MS/MS,PAC and ARR was 0.739,0.659,0.723,0.943,respectively.The cutoff values for them were 5.1μg/24 h,11.6μg/24 h,27.6 ng/dL and 23.2 ng·dL^-1(/μg·L^-1·h^-1),respectively.③Both UARRCLIA and UARRLC-MS/MS performed as well as ARR in PA screening.AUC of UARRCLIA was 0.924 at the cutoff value of 1.75μg·24h^-1(/μg·L^-1·h^-1).While AUC of UARRLC-MS/MS was 0.906 at the cutoff value of 4.63μg·24h^-1(/μg·L^-1·h^-1).AUC of UACLC-MS/MS in high urine sodium subgroup was 0.708 at the cutoff of 14.9μg/24 h.④The diagnostic efficiency of UAC made no difference after sodium intake increased to 130 mmol/24 h or higher.【Conclusion】UAC alone is of little clinical value compared to ARR in PA screening and can serve as a supplementary indi⁃cator currently.But UARR,a combintion of UAC and plasma renin activity(PRA),is as valuable as ARR for screening PA.The optimal cutoff values of UACLC-MS/MS and UACCLIA are 11.6μg/24 h,5.1μg/24 h,respectively.The optimal cutoff values of UARRLC-MS/MS and UARRCLIA are 4.63μg·24 h^-1/(μg·L^-1·h^-1)and 1.75μg·24 h^-1/(μg·L^-1·h^-1),respec⁃tively.Besides,significant bias of UAC observed in CLIA and LC-MS/MS results indicates that appropriate definition of cutoff value and reference range for each method are mandatory.