Mineralocorticoid Receptor Antagonists Decrease the Rates of Positive Screening for Primary Aldosteronism

Abstract

Objective: Mineralocorticoid receptor antagonists (MRAs) are effective in patients with resistant hypertension and/or primary aldosteronism (PA). Screening for PA should ideally be conducted after stopping medications that might interfere with the renin-angiotensin-aldosterone system, but this is challenging in patients with recalcitrant hypertension or hypokalemia. Herein, we aimed to evaluate the impact of MRAs on PA screening in clinical practice.

Methods: We conducted a retrospective cohort study of patients with hypertension who had plasma aldosterone and renin measurements before and after MRA use in a tertiary referral center, over 19 years.

Results: A total of 146 patients, 91 with PA, were included and followed for up to 18 months. Overall, both plasma renin and aldosterone increased after MRA initiation (from median, interquartile range: 0.5 [0.1, 0.8] to 1.2 [0.6, 4.8] ng/mL/hour and from 19.1 [12.9, 27.7] to 26.4 [17.1, 42.3] ng/dL, respectively; P<.0001 for both), while the aldosterone/renin ratio (ARR) decreased from 40.3 (18.5, 102.7) to 23.1 (8.6, 58.7) ng/dL per ng/mL/hour (P<.0001). Similar changes occurred irrespective of the MRA treatment duration and other antihypertensives used. Positive PA screening abrogation after MRA initiation was found in 45/94 (48%) patients. Conversely, 17% of patients had positive PA screening only after MRA treatment, mostly due to correction of hypokalemia. An initially positive screening test was more likely altered by high MRA doses and more likely persistent in patients with confirmed PA or taking beta-blockers.

Conclusion: MRAs commonly reduce ARR and the proportion of positive PA screening results. When PA is suspected, screening should be repeated off MRAs.

Abbreviations: ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARR = aldosterone/renin ratio; DRC = direct renin concentration; MRA = mineralocorticoid receptor antagonist; PA = primary aldosteronism; PAC = plasma aldosterone concentration; PRA = plasma renin activity; RAAS = renin-angiotensin-aldosterone system.

Fig. 1.

Selection of study participants. MRA = mineralocorticoid receptor antagonist; PAC = plasma aldosterone concentration.

Fig. 2.

Comparison of plasma renin and aldosterone changes after mineralocorticoid receptor antagonist (MRA) initiation between patients with and without primary aldosteronism (PA). Changes of: (A) plasma aldosterone concentration (PAC); (B) plasma renin activity (PRA); (C) direct renin concentration (DRC); and (D) aldosterone-to-renin ratio (ARR) in patients with PA (white boxes) and without PA (gray boxes) from baseline to the last follow-up visit after initiation of MRA therapy. Number of patients: total PA patients, n = 91 (panels A and D); with PRA, n = 76; with DRC, n = 15: patients without PA, n = 55 (panels A and D); with PRA, n = 38; with DRC, n = 17. To calculate ARR in all cases, DRC was converted to PRA by dividing by 8. Comparisons are based on two-way analysis of variance tests. Significant interactions were found between the changes of PRA and ARR and the two groups (P = .02 and .006, respectively). a, P<.05; b, P<.01; c, P<.001; d, P<.0001. *, ng/dL per ng/mL/h.

Fig. 3.

Dose-dependent changes of plasma renin and aldosterone during treatment with mineralocorticoid receptor antagonist (MRAs). Comparisons of: (A) plasma aldosterone concentration (PAC); (B) plasma renin activity (PRA); (C) direct renin concentration (DRC); and (D) aldosterone-to-renin ratio (ARR) between baseline and the last follow-up visit, divided into three groups based on the daily dose of MRAs: Group 1, <50 mg/day (total n = 80: PRA, n = 62; DRC, n = 18); Group 2, 50–100 mg/day (total n = 49: PRA, n = 37; DRC, n = 12); Group 3, >100 mg/day (total n = 17: PRA, n = 15; DRC, n = 2). To calculate ARR in all cases, DRC was converted to PRA by dividing by 8. Statistical significance based on the Wilcoxon signed rank test are shown as follows: a, P<.01; b, P<.001; c, P<.0001. * ng/dL per ng/mL/h.