PSUN68 Finerenone for Primary Aldosteronism: A Novel Mineralocorticoid Receptor Antagonist

Abstract

Abstract Background In primary aldosteronism (PA), aldosterone is inappropriately released into the systemic circulation and binds to the mineralocorticoid receptor (MR) in the distal tubule and collecting duct of the kidney. As a result, there is sodium reabsorption and potassium wasting leading to extracellular volume expansion, hypertension, hypokalemia, and, ultimately, suppressed renin. For medication management of aldosterone-producing adenomas with MR antagonists, spironolactone or eplerenone, are recommended. Finerenone is a novel, selective, non-steroidal MR antagonist approved July 2021 to reduce the risk of kidney and heart complications in patients with diabetic kidney disease. Interestingly, finerenone is at least as potent as spironolactone, and more selective for the MR (at least 500-fold) than eplerenone (1). We present a case using finerenone for the treatment of PA. Clinical Case OA 62-year-old male with CKD Stage G4/A3, T2DM, obesity, refractory hypertension and persistent hypokalemia underwent two radiofrequency ablations of a left adrenal nodule for the management of PA. Because of biochemical evidence for persistent hyperaldosteronism, pharmacologic therapy was initiated with eplerenone, which was chosen over spironolactone based on tolerability profile. Other antihypertensives included labetalol and nifedipine. Eplerenone was gradually titrated to 150 mg twice daily along with potassium replacement, but PRA remained below goal at 0.35 ng/mL/h with average BP 164/97 mmHg lying, 169/92 mmHg sitting, and 139/90 mmHg standing. Other pertinent labs included average SCr 4.62 mg/dL and eGFR 15 mL/min/1.73m2. A joint decision was made to replace eplerenone with finerenone 10 mg once daily. Two weeks after starting finerenone, PRA increased to 0.59 ng/mL/h, and SCr, eGFR, and potassium were 4.79 mg/dL, 14 mL/min/1.73m2, and 4.2 mEq/L, respectively. BP was 165/92 mmHg lying, 154/92 mmHg sitting, and 118/82 mmHg standing. Finerenone was increased to 20 mg once daily with close follow-up monitoring revealing an average PRA 0.42 ng/mL/h, SCr 4.28 mg/dL, eGFR 16 mL/min/1.73m2, potassium 3.5 mEq/L, and average BP 163/90 mmHg lying, 164/94 mmHg sitting, and 149/84 mmHg standing. Finerenone was well-tolerated and no changes were made to potassium replacement during this time. Conclusion Current MR antagonists, spironolactone and eplerenone, have concerns with tolerability due to minimal selectivity and efficacy, respectively. A new generation of MR antagonists, such as finerenone, with high potency and selectivity may lead to practice changes for management of PA. Based on our patient, finerenone increased PRA and similarly controlled BP compared to eplerenone. Further research will be required to evaluate finerenone for PA as a safe, effective, and convenient alternative MR antagonist, specifically with evaluation of dose-dependent effects beyond 20 mg daily as currently described in the literature. Reference 1. Kolkhof P, Bärfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234(1): T125-T140. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.