Abstract: TH-PO0847
Sustained Reversal of Hyperaldosteronism After Aldosterone Synthase Inhibitor Exposure in a Patient with Primary Aldosteronism and CKD: Implications for Targeted Adrenal Therapy
Session Information
- Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
- 1900 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)
Authors
- Vadpey, Omid, University of California San Francisco, San Francisco, California, United States
- Jamshidian, Mitra S., University of California San Francisco, San Francisco, California, United States
- Brown, Morris, University of London, London, England, United Kingdom
- Sam, Ramin, University of California San Francisco, San Francisco, California, United States
Introduction
Aldosterone synthase inhibitors (ASIs) represent a novel therapeutic alternative to mineralocorticoid receptor blockade. Clinical trials have demonstrated efficacy in resistant hypertension; however, their long-term impact on adrenal zona glomerulosa function remains incompletely understood. We present a 46-year-old male with primary aldosteronism (PA) who was treated for 6 months with an ASI and developed persistent suppression of serum aldosterone levels. This observation contrasts with the rapid reversibility of short-term aldosterone synthase inhibition and illustrates the potential for prolonged adrenal remodeling by the new class of drugs.
Case Description
A 46-year-old male with CKD and PA (plasma aldosterone 18 ng/dl, renin activity 0.24 ng/ml/hr) was enrolled in the SPARK phase 2a trial of baxdrostat in PA. The drug was titrated over 12 weeks from 2 mg to 8 mg daily, beginning 3/2023, and continued until 9/2023, when he developed acute kidney injury, prompting discontinuation of baxdrostat. In 12/2025, the BP was 119/79 mmHg, on lisinopril 20 mg daily, nifedipine 60 mg daily, and carvedilol 25 mg twice daily. At 1 and 2 years after participation in SPARK, plasma aldosterone remained persistently suppressed, at <3 and 3.4 ng/dL, respectively; plasma renin activity remained elevated, at 10.6 and 43 ng/ml/hr.
Discussion
Recent clinical trials of ASIs have shown a substantial decrease of BP in patients with treatment-resistant hypertension. Preliminary data also support the potential role of these agents in PA. Here, we report a patient with persistent aldosterone suppression more than 2 years after discontinuation of baxdrostat. Prior animal studies have shown cellular apoptosis of the zona glomerulosa following ASI treatment, providing a potential mechanistic explanation for our observation. This case represents a novel clinical observation which may inspire further mechanistic research and inform the long-term management of PA.