Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 66; no. 3; pp. 483 - 492
• Main Authors: Guo, Zeng, Poglitsch, Marko, McWhinney, Brett C, Ungerer, Jacobus P J, Ahmed, Ashraf H, Gordon, Richard D, Wolley, Martin, Stowasser, Michael
• Format: Journal Article
• Language: English
• Published: England American Association for Clinical Chemistry, Inc 01.03.2020; Oxford University Press
• Subjects: Aldosterone; Analysis; Angiotensin; Angiotensin II; Antihypertensives; Assaying; Biosynthesis; Consistency; Diagnosis; Diagnostic systems; Endocrine disorders; Enzymes; Equilibrium; Ethylenediaminetetraacetic acid; Fludrocortisone; Hyperaldosteronism; Hypertension; Low concentrations; Measurement; Medical diagnosis; Peptides; Physiological effects; Physiological factors; Physiology; Posture; Renin; Sensitivity; Australia; Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS); Aldosterone to Angiotensin II Ratio (AA2R); Aldosterone to Renin Ratio (ARR); Fludrocortisone Suppression Testing (FST); Primary Aldosteronism (PA)
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/hvaa001

Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system. Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST). Peripheral levels of eqAngII, plasma renin activity (PRA) and direct renin concentration (DRC) were measured. EqAngII showed good consistency with DRC and PRA independent of PA diagnosis, posture, and fludrocortisone administration. EqAngII showed close (P < 0.01) correlations with DRC (r = 0.691) and PRA (r = 0.754) during FST. DRC and PRA were below their assays' functional sensitivity in 43.9% and 15.1%, respectively, of the total 312 samples compared with only 7.4% for eqAngII (P < 0.01). Bland-Altman analysis revealed an overestimation of PRA and DRC compared with eqAngII in a subset of samples with low renin levels. The AA2R showed not only consistent changes with the ARR but also close (P < 0.01) correlations with the ARR, whether renin was measured by DRC (r = 0.878) or PRA (r = 0.880). Dynamic changes of eqAngII and the AA2R show good consistency and close correlations with renin and the ARR. The eqAngII assay shows better sensitivity than DRC and PRA assays, especially at low concentrations. Whether the AA2R can reduce the impact of some factors that influence the diagnostic power of the ARR warrants further study.