Feasibility Of Screening Primary Aldosteronism By Aldosterone-to-Direct Renin Concentration Ratio Derived From Chemiluminescent Immunoassay Measurement:Diagnostic Accuracy And Cutoff Value

Background: Primary aldosteronism(PA)is characterized by excessive and autonomous aldosterone production and suppressed plasma renin and leads to various symptoms including hypertension and hypokalemia and inhibition of renin activity.PA is a curable and the most common form of secondary hypertension.The U.S.guidelines for PA have reported that is approximately about 5-10%.More importantly,patients with PA are associated with significant higher risk of cardiovascular events and target organ damage than patients with primary hypertension(PH)at comparable blood pressure level.Since the treatment of patients with PA is different from that of patients with PH,early diagnosis of PA is extremely important for appropriate targeted management and improvement of prognosis.According to Endocrine Society guidelines,a reliable and convenient screening test is essential for diagnosis of PA.In 1981,Hiramatsu et al,Firstly recommended the use of aldosterone-to-plasma renin activity ratio(ARR)is considered to be the reliable screening test,this method has been widely recommended at home and abroad since then.Aldosterone-to-plasma renin activity ratio(ARR)is considered tond plasma renin activity(PRA)are derived from traditional radioimmunoassay(RIA).PRA is indirectly estimated by efficiency of generating angiotensin I from angiotensinogen that is probably affected by the concentration ofangiotensinogen in plasma.In addition,this manual method is time consuming,and produces radioactive waste.Nowadays,aldosterone-to-direct renin concentration ratio(ADRR)is developed and proposed to replace ARR as the screening test for PA with higher accuracy and reproduction efficacy.ADRR is calculated by direct renin concentration(DRC)measured directly using chemiluminescent immunoassay(CLIA)on automated platform,this method is reproducible,simpler,cheaper and less time-consuming.Previous researches verified the relationship between DRC measured by RIA and PRA measured by CLIA.However,ADRR has not been widely used in diagnosis of PA,because the accurate cutoff value and diagnostic efficiency of ADRR for screening PA are still unclear.Objective: The purpose of cutoff value of ADRR as screening test for PA by adequate sample size.Method: We collected clinical characteristics of 450 patients with suspected PA from the hypertension center of First Affiliated Hospital of DaLian Medical University between March 2016 and July 2018.All patients underwent prepare works before performing screening test and confirmatory test(intravenous saline loading test).For those patients with unclear diagnosis after intravenous saline loading test,captopril challenge test was performed.In the present study,PRA,DRC and PAC were examined by both RIA and CLIA simultaneously during screening and confirmatory tests,and PA was diagnosed by RIA at confirmatory test.The relationship between PRA and DRC,PAC measured by different methods and diagnostic accuracy,optimal cutoff value,sensitivity and specificity of ADRR and ARR as screening test for PA were analyzed statistically.Results: In our study,there were 386 patients diagnosed with PH and 64 patients with PA.PRA showed a significant within-patient correlation with DRC(r=0.88,P<0.001),and the linear regression formula was Y=0.9573+0.8925×X.PACs measured by different methods also showed a significant within-patient correlation(r=0.80,P<0.001),and the linear regression formula was Y=0.4431+0.7562×X.There was no significant difference between the diagnostic accuracies of ADRR and ARRBland-Altman plot of ARR and ADRR also showed a very good agreement.The optimal cutoff value of ADRR was 2.93(ng/dL)/(mU/L),sensitivity 80.33%,specificity 92.11%,and the optimal cutoff value of ARR was 25.28(ng/dL)/(ng/mL/h),sensitivity 76.92%,specificity 93.38%.Conclusion: Both PRA and DRC,and PACs measured by different methods showed significant positive correlations.We demonstrated an optimal cutoff value of ADRR,2.93(ng/dL)/(mU/L),for screening PA with high sensitivity and specificity.Our results are of clinical importance for accelerating the extensively use of ADRR as a screening test for PA in daily practice.