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      Comparisons of plasma aldosterone and renin data between an automated chemiluminescent immunoanalyzer and conventional radioimmunoassays in the screening and diagnosis of primary aldosteronism

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          Abstract

          Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed ® immunoanalyzer facilitated the determination, but relations between Accuraseed ® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed ® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR ® RIA and SPAC ®-S Aldosterone kits, respectively. The relations between Accuraseed ® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed ® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed ® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed ® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed ® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed ® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays.

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          Most cited references28

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          The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

          To develop clinical practice guidelines for the management of patients with primary aldosteronism.
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            The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019)

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              Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism.

              The aim of this report was to show that the rate of cardiovascular events is increased in patients with either subtype of primary aldosteronism (PA). Primary aldosteronism involves hypertension (HTN), hypokalemia, and low plasma renin. The two major PA subtypes are unilateral aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia. During a three-year period, the diagnosis of PA was made in 124 of 5,500 patients referred for comprehensive evaluation and management. Adenomas were diagnosed in 65 patients and idiopathic hyperaldosteronism in 59 patients. During the same period, clinical characteristics and cardiovascular events of this group were compared with those of 465 patients with essential hypertension (EHT) randomly matched for age, gender, and systolic and diastolic blood pressure. A history of stroke was found in 12.9% of patients with PA and 3.4% of patients with EHT (odds ratio [OR] = 4.2; 95% confidence interval [CI] 2.0 to 8.6]). Non-fatal myocardial infarction was diagnosed in 4.0% of patients with PA and in 0.6% of patients with EHT (OR = 6.5; 95% CI 1.5 to 27.4). A history of atrial fibrillation was diagnosed in 7.3% of patients with PA and 0.6% of patients with EHT (OR = 12.1; 95% CI 3.2 to 45.2). The occurrence of cardiovascular complications was comparable in both subtypes of PA. Patients presenting with PA experienced more cardiovascular events than did EHT patients independent of blood pressure. The presence of PA should be detected, not only to determine the cause of HTN, but also to prevent such complications.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: Project administrationRole: ResourcesRole: Writing – original draft
                Role: Investigation
                Role: Investigation
                Role: Formal analysisRole: Writing – review & editing
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Resources
                Role: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 July 2021
                2021
                : 16
                : 7
                : e0253807
                Affiliations
                [1 ] Research Support Center, Shizuoka General Hospital, Shizuoka, Shizuoka, Japan
                [2 ] Center for Diabetes, Endocrinology and Metabolism, Shizuoka General Hospital, Shizuoka, Shizuoka, Japan
                [3 ] Department of Clinical Laboratory Medicine, Shizuoka General Hospital, Shizuoka, Shizuoka, Japan
                [4 ] Department of Medical Genetics, Shizuoka General Hospital, Shizuoka, Shizuoka, Japan
                Max Delbruck Centrum fur Molekulare Medizin Berlin Buch, GERMANY
                Author notes

                Competing Interests: FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan ( http://ffwk.fujifilm.co.jp) provided the authors an Accuraseed ® automated chemiluminescent enzyme immunoanalyzer, and Accuraseed ® Aldosterone and Accuraseed ® Renin kits to perform this study. The company did not provide the authors grants, royalties or licenses, consulting fees, payment or honoraria, support for attending meeting and/or travel, or stock or stock options. There are no patents planned, issued, or pending in relation to this study. The company had no role in the study design; collection, analysis, and interpretation of data; writing of the paper; and/or decision to submit for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Sharing the data of the present study is restricted by the Shizuoka General Hospital Research Ethical Committee following the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan as described in the Data Availability statement. The de-identified dataset of this study is available on request to Shizuoka General Hospital Research Ethical Committee, Email: chiken-sougou@ 123456shizuoka-pho.jp . All requests must include an analysis plan and the plan must be approved by this ethics committee. Except as described above, none of the authors have any competing interests associated with this research.

                Author information
                https://orcid.org/0000-0003-4000-6215
                https://orcid.org/0000-0002-4876-446X
                Article
                PONE-D-21-05833
                10.1371/journal.pone.0253807
                8270132
                34242264
                ab5f6ebe-4d1d-4ff3-91b4-03511d6aac33
                © 2021 Tamura et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 February 2021
                : 13 June 2021
                Page count
                Figures: 5, Tables: 2, Pages: 23
                Funding
                This study was performed as a collaboration with FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan ( http://ffwk.fujifilm.co.jp), which provided the authors an Accuraseed ® automated chemiluminescent enzyme immunoanalyzer, and Accuraseed ® Aldosterone and Accuraseed ® Renin kits to perform this study. The company had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Biochemistry
                Hormones
                Lipid Hormones
                Aldosterone
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Physical Sciences
                Mathematics
                Probability Theory
                Probability Distribution
                Normal Distribution
                Medicine and Health Sciences
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                Health Care Policy
                Screening Guidelines
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Veins
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Veins
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Biology and Life Sciences
                Physiology
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                Custom metadata
                The Ethical Guidelines for Medical and Health Research Involving Human Subjects, issued by the Ministry of Health, Labour and Welfare, Japan, stated that the individual providing existing specimens or information should obtain at least oral informed consent from participants. The fact that existing specimens or information are to be provided to other research implementing entity(s) should be included in the consent. When the provisional English translation of these guidelines, which has been abolished, was made public in March 2015, the informed consent was not required if the existing specimens or information to be provided had been anonymized. However, the guidelines were amended in response to the effectuation of amendment of Personal Information Protection Law in 2017, and restrictions were applied to providing anonymized specimens or information in Japan if they were linkable (official English translations of the amended guidelines are currently not available). In the present study, anonymization was linkable because a decoding index was made. Conducting the present study was approved by the Shizuoka General Hospital Research Ethical Committee on the condition that all future studies utilizing de-identified data obtained in the present study must be approved by the Shizuoka General Hospital Research Ethical Committee in advance, and written informed consent was obtained from each participant on this condition. Sharing a de-identified data set is restricted by the Shizuoka General Hospital Research Ethical Committee in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects. The de-identified dataset of this study is available on request to Shizuoka General Hospital Research Ethical Committee, Email: chiken-sougou@ 123456shizuoka-pho.jp . All requests must include an analysis plan and the plan must be approved by this ethics committee.

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