PotassiumNEW2026-08

Macrolide-induced aldosterone suppression as a functional marker of KCNJ5-mutated aldosterone-producing adenoma: a proof-of-concept clinical and experimental study (MAPA study).

Rossi Gian Paolo, Caroccia Brasilina, Bressan Alessandro, Byiringiro Clement et al. — European journal of endocrinology

Summary

This study explored a new way to identify a specific genetic cause of primary aldosteronism, a common curable form of high blood pressure. Researchers found that a single dose of a common antibiotic, roxithromycin, could selectively reduce aldosterone levels in patients with a particular genetic mutation (KCNJ5) linked to this condition. This finding could help doctors better diagnose and tailor treatment for these patients, who often experience issues with potassium balance.

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Key points

Primary aldosteronism, a cause of high blood pressure, can lead to low potassium levels.
This study investigated if a macrolide antibiotic could help identify a specific genetic mutation (KCNJ5) in patients with this condition.
A single dose of roxithromycin selectively lowered aldosterone in patients with the KCNJ5 mutation, suggesting it could be a diagnostic tool.
Identifying this mutation helps doctors provide more precise treatment for high blood pressure and related potassium imbalances.

What the study looked at

What question did the study ask? This study aimed to determine if a common antibiotic, roxithromycin, could help identify a specific genetic cause of primary aldosteronism (PA), a condition where the body produces too much aldosterone, often leading to high blood pressure and low potassium. They specifically looked for a mutation in the KCNJ5 gene, which makes aldosterone production sensitive to certain drugs. How was it studied? Researchers at a specialized hypertension center gave a single oral dose of roxithromycin to 373 patients with high blood pressure who were being screened for PA. They then measured changes in aldosterone levels, blood pressure, and other markers within each patient. Mouse studies were also conducted to understand the drug's effects on blood pressure. What did it find? The study found that roxithromycin significantly reduced aldosterone levels only in patients with PA who had the KCNJ5 gene mutation. While it didn't lower blood pressure in these specific patients, it did cause a small blood pressure decrease in other hypertensive patients without PA, through a different mechanism. This suggests roxithromycin could serve as a functional marker to precisely identify KCNJ5-mutated PA.

Dietary takeaway

While this study is highly specialized, it indirectly highlights the importance of maintaining proper potassium balance, as primary aldosteronism often leads to low potassium. For the general public, it reinforces that medical conditions affecting hormones like aldosterone can impact electrolyte levels. This research is a step towards more precise diagnosis for a specific type of high blood pressure, which could ultimately lead to better management of related issues like potassium imbalances. Remember, this is one study, and dietary potassium intake should always be discussed with a healthcare professional, especially if you have a medical condition.

Abstract

OBJECTIVE: Primary aldosteronism (PA), the most common curable form of hypertension, is frequently caused by aldosterone-producing adenomas (APAs) harbouring KCNJ5 mutations that render aldosterone synthesis sensitive to macrolides in vitro. This study aimed to evaluate whether a single dose of roxithromycin reduces plasma aldosterone concentration (PAC) and blood pressure (BP) in patients with KCNJ5-mutated APA, and to characterize the haemodynamic effects of macrolides in mice. DESIGN: Prospective, within-patient pharmacologic challenge. METHODS: At the specialized Hypertension Center, University of Padua, eligible consecutive hypertensive patients screened for PA underwent a pharmacologic challenge with a single oral dose of roxithromycin to investigate the within-patient changes in PAC, active renin, cortisol, and BP. RESULTS: Among 373 challenged patients, 18 had KCNJ5 (G151R or L168R)-mutated APA, 25 had wild-type APA, and 307 had no PA. Roxithromycin reduced PAC (P < .001) only in APA with KCNJ5 mutation, albeit it did not lower BP values. However, it produced a small BP decrease in non-PA hypertensive patients. Mouse studies showed that this BP lowering can be due to macrolide-induced attenuation of angiotensin II actions involving enhancement of endothelium- and nitric oxide-dependent vasodilation. CONCLUSIONS: The selective suppression of aldosterone secretion with roxithromycin in KCNJ5-mutated APA in vivo, which aligns with ex vivo mechanistic data, can represent a functional marker of KCNJ5 mutations and could help guide precision subtyping of PA patients. Macrolides also exhibit an aldosterone-independent antihypertensive effect in non-PA patients, which involves nitric oxide-dependent vasodilation.

View on PubMed →DOI: 10.1093/ejendo/lvag161