Will spironolactone alter the renin-aldosterone ratio?

From the Guidelines

Yes, spironolactone will alter the renin-aldosterone ratio, making it an unreliable test for primary aldosteronism screening while on this medication. Spironolactone is a potassium-sparing diuretic that acts as an aldosterone antagonist, blocking aldosterone receptors in the kidneys. This blockade leads to a compensatory increase in renin and aldosterone levels through the feedback mechanism of the renin-angiotensin-aldosterone system. Specifically, spironolactone typically causes renin levels to rise more significantly than aldosterone, resulting in a falsely lowered aldosterone-to-renin ratio. For accurate diagnostic testing, spironolactone should be discontinued for at least 4-6 weeks before measuring the renin-aldosterone ratio, as recommended by the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1. If blood pressure control is needed during this washout period, alternative antihypertensives that minimally affect the ratio (such as calcium channel blockers like verapamil or alpha-blockers like doxazosin) can be used instead. It is essential to monitor serum potassium levels and renal function during spironolactone treatment, especially in patients with kidney disease or those taking other medications that may increase the risk of hyperkalemia, as noted in the 2019 guideline for the management of central serous chorioretinopathy 1. The use of spironolactone in patients with primary aldosteronism should be carefully considered, and the benefits and risks should be weighed, as discussed in the 2018 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Some key points to consider when using spironolactone include:

• Monitoring serum potassium levels and renal function during treatment
• Avoiding the use of spironolactone in patients with kidney disease or those taking other medications that may increase the risk of hyperkalemia
• Discontinuing spironolactone for at least 4-6 weeks before measuring the renin-aldosterone ratio
• Using alternative antihypertensives that minimally affect the ratio during the washout period
• Weighing the benefits and risks of using spironolactone in patients with primary aldosteronism.

Overall, spironolactone can be a useful medication for treating certain conditions, but its use requires careful consideration and monitoring to minimize the risk of adverse effects, as noted in the 2024 guideline for the treatment of central serous chorioretinopathy 1.

From the FDA Drug Label

Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule.

Aldosterone antagonist activity: Increased levels of the mineralocorticoid, aldosterone, are present in primary and secondary hyperaldosteronism.

By competing with aldosterone for receptor sites, Spironolactone provides effective therapy for the edema and ascites in those conditions.

The use of spironolactone will alter the renin-aldosterone ratio because it acts as an aldosterone antagonist. As spironolactone competes with aldosterone for receptor sites, it will decrease the effect of aldosterone, which can lead to an increase in renin levels as a compensatory response. This is because the decrease in aldosterone effect will reduce the negative feedback on renin release, resulting in an increased renin-aldosterone ratio 2.

• Key points:
  • Spironolactone is an aldosterone antagonist
  • It competes with aldosterone for receptor sites
  • This decreases the effect of aldosterone and can lead to an increase in renin levels
  • Resulting in an increased renin-aldosterone ratio

From the Research

Effect of Spironolactone on Renin-Aldosterone Ratio

• Spironolactone is known to affect the renin-aldosterone axis, but its impact on the renin-aldosterone ratio is complex and depends on various factors, including the underlying condition of the patient 3, 4, 5.
• In patients with primary hyperaldosteronism, spironolactone treatment can lead to a sustained impairment of the aldosterone secretory response to normalized plasma renin and potassium levels, but not to ACTH stimulation 3.
• The aldosterone-to-renin ratio (ARR) is an index for inappropriate aldosterone activity and can be used to predict the response to spironolactone in hypertensive patients 4, 5.
• Studies have shown that a raised ARR is highly predictive of nonsuppression of plasma aldosterone, suggesting primary aldosteronism, and may be a good index to help predict the response to spironolactone 4, 5.
• However, the relationship between ARR and the response to spironolactone is not always straightforward, and other factors such as low renin activity and potassium levels can also influence the response to spironolactone 5, 6, 7.

Clinical Implications

• Spironolactone can be an effective antihypertensive agent in patients with a raised aldosterone-to-renin ratio, particularly in those with primary aldosteronism 4, 5.
• The use of spironolactone in patients with resistant hypertension and a low plasma renin activity may be beneficial, even in the absence of hypokalaemia 7.
• Close monitoring of serum electrolytes and renal function tests is recommended in patients on spironolactone therapy, especially those with impaired renal function or those taking other medications that can affect electrolyte balance 6.