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Test characteristics of the aldosterone-to-renin ratio as a screening test for primary aldosteronism

Jansen, Pieter M.a; van den Born, Bert-Jan H.b; Frenkel, Wijnanda J.b; de Bruijne, Emile L.E.c; Deinum, Jaapd; Kerstens, Michiel N.e; Smulders, Yvo M.f; Woittiez, Arend Jang; Wijbenga, Johanna A.M.h; Zietse, Roberta; Danser, A.H. Jana; van den Meiracker, Anton H.a

doi: 10.1097/HJH.0b013e3283656b54
ORIGINAL PAPERS: Aldosteronism

Background: The aldosterone-to-renin ratio (ARR) is a widely used screening test for primary aldosteronism. Current guidelines recommend a cut-off value of 91 pmol/mU. Studies on its sensitivity, specificity, reproducibility and the role of medication have been conflicting. We prospectively assessed the test characteristics of the ARR and the effect of combination antihypertensive treatment.

Methods: In 178 patients with persistent hypertension despite the use of at least two antihypertensives, plasma renin and aldosterone were assessed twice within an interval of 4 weeks. All patients underwent an intravenous salt loading test. A posttest plasma aldosterone exceeding 235 pmol/l was considered diagnostic for primary aldosteronism. ARR was repeated after 4 weeks of standardized treatment with a calcium channel blocker and/or α-adrenergic-receptor blocker.

Results: The prevalence of primary aldosteronism was 15.2%. The median ARR was 35.0 (interquartile range 16.2–82.0) in primary aldosteronism versus 7.1 (2.2–17.5) pmol/mU in essential hypertensive patients (P < 0.001). Under random medication, the ARR had 22.2% sensitivity and 98.7% specificity. On standardized treatment, the ARR rose from 9.6 (2.5–24.8) to 21.4 (10.8–52.1) (P < 0.001). Multivariate regression showed that angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II-receptor blockers were responsible for the lower ARR during random treatment. The area under the receiver operating characteristic curve was, however, similar under random and standardized treatment (84 vs. 86%, respectively, P = 0.314). Bland–Altman plots showed an almost five-fold difference in ARR values taken under the same conditions.

Conclusion: ARR sensitivity for primary aldosteronism is low when the recommended cut-off is used. Reproducibility is also poor, stressing the need for alternative screening tests.

aErasmus Medical Centre, Department of Internal Medicine, Rotterdam

bAcademic Medical Centre, Department of Internal Medicine, Amsterdam

cRed Cross Hospital, Department of Internal Medicine, Beverwijk

dRadboud University Nijmegen Medical Centre, Department of Internal Medicine

eUniversity of Groningen, University Medical Centre Groningen, Department of Endocrinology, Groningen

fVrije Universiteit Medical Centre, Department of Internal Medicine, Amsterdam

gZiekenhuis Groep Twente, Department of Internal Medicine, Almelo

hVlietland Hospital, Department of Internal Medicine, Schiedam, The Netherlands

Correspondence to Anton H. van den Meiracker, MD, PhD, Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Room D432, Erasmus MC, ‘s Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Tel: +31 10 7034220; e-mail:

Abbreviations: AB, α-adrenergic receptor blocker; ACEi, angiotensin-converting enzyme inhibitor; APA, aldosterone-producing adenoma; ARB, angiotensin II receptor blocker; ARR, aldosterone-to-renin ratio; AUC, area under the curve; BB, β-adrenergic receptor blocker; CCB, calcium channel blocker; PAC, plasma aldosterone concentration; RAS, renin–angiotensin system; ROC, receiver operating curve

Received 10 January, 2013

Revised 9 May, 2013

Accepted 26 July, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins