Abstract
Background: Mineralocorticoid receptor antagonists (MRAs) are the mainstay of medical therapy for primary aldosteronism (PA), and MRAs also benefit patients with other forms of resistant hypertension and cardiovascular disorders. MRAs impact the renin-angiotensin-aldosterone system (RAAS), raising concerns regarding the accuracy of PA screening. The rate of false negative and/or false positive screening for PA in patients taking MRAs has not been systematically evaluated. Herein, we assessed the alterations of both renin and aldosterone after MRA initiation in a large cohort of patients with hypertension.
Patients and Methods: We conducted a retrospective cohort study of patients with hypertension seen in a tertiary referral center. We employed our center’s database search engine to identify adults with hypertension who were treated with MRAs. Of these, we included patients who had renin and aldosterone measured both before and after MRA treatment. We excluded patients with adrenal cortical cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. PA screening was considered positive when plasma aldosterone concentration (PAC) was 10 ng/dL, plasma renin activity (PRA) was 1.0 ng/mL/h, and the aldosterone-to renin ratio (ARR) was 20. Mann-Whitney test and Wilcoxon signed rank test were employed to compare independent or paired groups, respectively.
Results: In total, 109 patients (57 women), mean age 55+/-13 years were included. Of these, 40% had confirmed PA (14% unilateral and 26% bilateral); in 38% PA was excluded; and in the remaining 22%, testing for PA was incomplete. On average, patients were on 3 +/- 1.6 antihypertensive agents; 60% of patients were prescribed beta blockers, 49% K+-wasting diuretics and 35% were on K+ supplements. Both PAC and PRA increased after MRA treatment (from 19.0 [12.6, 26.7] to 26.3 [17.2, 36.2]; and from 0.6 [0.10, 0.80] to 1.00 [0.60, 2.80], respectively, p < 0.0001 for both), while ARR decreased from 42.5 [18.5, 109.8] to 24.0 [10.9, 55.5] (p = 0.003). Of 71 patients with positive PA screening at baseline, 31 (43.7 %) no longer met positive screening criteria during MRA therapy. Conversely, 7 of 38 patients (18 %) with negative screening at baseline met criteria for positive PA screening while on MRA treatment, including 5 patients with a PAC > 20 ng/dL along with suppressed renin. The impact on PA screening accuracy remained similar irrespective of the MRA dose, duration of treatment, changes in concomitant antihypertensive drugs, or hypertension type.
Conclusions: Commonly, MRA treatment leads to renin elevation, ARR reduction, and consequential false negative PA screening. In a minority of patients, MRA therapy can be followed by aldosterone elevations asynchronous from renin, possibly via short feedback loops, mimicking PA. Whenever possible, PA testing should be conducted after MRA discontinuation.
Hyperparathyroidism in Patients with Primary Aldosteronism: Cross-Sectional and Interventional Data from the GECOH Study
