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

Abstract

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. 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. 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. 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.