When to check the aldosterone (a hormone) to renin (an enzyme) ratio?

From the Guidelines

The aldosterone/renin ratio should be checked when evaluating patients for primary aldosteronism, particularly in those with resistant hypertension, hypertension with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, or hypertension with a family history of early-onset hypertension or cerebrovascular accident before age 40, as recommended by the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.

Indications for Testing

The following conditions indicate the need for aldosterone/renin ratio testing:

• Resistant hypertension (requiring three or more medications)
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Hypertension with adrenal incidentaloma
• Hypertension with a family history of early-onset hypertension or cerebrovascular accident before age 40
• Hypertension and sleep apnea
• Hypertensive first-degree relatives of patients with primary aldosteronism ### Pre-Test Preparation Before testing, the following steps should be taken:
• Discontinue interfering medications: spironolactone, eplerenone, and amiloride for 4-6 weeks; diuretics, ACE inhibitors, and ARBs for 2 weeks; and beta-blockers, central alpha-2 agonists, and NSAIDs for 1-2 weeks
• Maintain a normal sodium diet
• Correct potassium levels before testing
• Collect blood samples mid-morning after the patient has been upright for at least 2 hours and seated for 5-15 minutes ### Interpretation of Results An elevated aldosterone/renin ratio suggests primary aldosteronism, which requires confirmation with additional testing such as salt loading or captopril suppression tests, as stated in 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 2.

Additional Considerations

The aldosterone/renin ratio can be influenced by the presence of very low renin levels, and the plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 2. The 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1 provide the most recent and highest quality evidence for the management of primary aldosteronism, and should be consulted for further guidance.

From the Research

When to Check Aldosterone/Renin Ratio

The aldosterone/renin ratio should be checked in the following situations:

• Resistant hypertension 3, 4, 5
• Hypertension with a first-degree relative with primary aldosteronism 4
• Hypokalemia 4, 6
• Presence of an adrenal nodule 4
• Atrial fibrillation 4
• Obstructive sleep apnea 4
• Family history of early stroke (i.e., younger than 40 years) 4

Key Considerations

• The aldosterone/renin ratio is a valuable screening test for primary aldosteronism 7
• An elevated aldosterone-renin ratio (greater than 30) indicates independent aldosterone secretion (i.e., aldosteronism) 4
• Confirmatory testing should be performed after a positive case detection 4, 6
• Adrenal computed tomography and adrenal vein sampling should be performed to differentiate unilateral from bilateral adrenal production of aldosterone 4, 6

Cutoff Values

• A ≥ 16.95 ng/dL had an odds ratio of 6.24 for primary aldosteronism 5
• A/PRA ≥ 29.88 or an A/PRC ≥ 2.44 had an odds ratio of 216.17 for primary aldosteronism diagnoses 5