Abstract
Background: Medical treatment with mineralocorticoid receptor antagonists (MRAs) is preferred for patients with primary aldosteronism (PA) who are not surgical candidates. Adequate mineralocorticoid receptor blockade, as suggested by renin elevation above suppression levels, has been associated with lower rates of cardiovascular and renal complications as compared with PA with sustained renin suppression.
Objectives: To assess the timeline and rates of achieving target renin levels in patients with PA and low renin hypertension treated with MRAs.
Patients and Methods: We conducted a retrospective cohort study of adult patients with hypertension who were treated with MRAs in an academic center between 2003-2019. Of these, we included patients who had suppressed renin at baseline, and repeated renin measurement(s) during MRAs therapy. Renin suppression was defined as plasma renin activity (PRA) 1.0 ng/mL/h or direct renin concentration (DRC) 8.0 pg/mL. We excluded patients with adrenal cancer, end-stage renal disease, exogenous glucocorticoids, and critically ill. Mann-Whitney test, Wilcoxon signed rank test, Chi-Square test and multiple logistic regression analysis were employed, as appropriate.
Results: So far, 89 patients (45 men), median age 56 (range, 19-84), have been included. Of these, 46% had confirmed PA; 25% had positive PA screening, but no confirmatory tests; and 29% had other forms of low-renin hypertension. On average, patients were on 2.9 1.6 antihypertensive agents; 62% of patients were prescribed beta blockers, and 38% were on K+ supplements. Overall, renin (PRA in 69 cases, and DRC in 20 cases) increased after MRA treatment (from 0.40 [0.10, 0.60] ng/mL/h to 1.10 [0.60, 2.23] ng/mL/h; and from 2.1 [2.1, 3.7] pg/mL to 5.7 [2.9, 16.7] pg/mL, respectively, p<0.0001 for both). The cumulative proportions of patients in whom renin reached target levels during MRA treatment were: 25% at 2 weeks; 38.9% at 1 month; 34.2% at 3 months; 39.5% at 6 months; and 47.2% at 1 year. Age, sex, race, blood pressure, use of beta blockers, renal function, serum K+ and aldosterone concentrations were similar between patients with target vs. suppressed renin. Multiple logistic regression analysis suggested that after adjusting for age and sex, higher MRA dose and higher BMI were associated with higher likelihood of achieving target renin during MRA therapy (odds ratio (95%CI): 1.021 (1.001-1.041) and 1.097 (1.008-1.193), respectively, p<0.05 for both); conversely, beta blockers use tended to be less often associated with target renin (odds ratio, 0.37 (0.13-1.008), p=0.052).
Conclusion: Although raising renin above suppression levels is important for reducing the cardiovascular risk associated with PA, this goal is achieved in less than half of patients, even after one year of treatment with MRAs, in an academic setting. Strategies for optimizing PA treatment are critically needed.
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