What is the importance of the aldosterone (a hormone) renin (an enzyme) ratio test in diagnosing primary aldosteronism in patients with resistant hypertension or young patients with hypertension and no family history of the condition?

Aldosterone-Renin Ratio Test: Critical Screening Tool for Primary Aldosteronism

Direct Answer

The aldosterone-renin ratio (ARR) is the most accurate and reliable screening test for primary aldosteronism, a condition affecting 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension, making it essential for identifying a potentially curable cause of hypertension that carries significantly higher cardiovascular risk than primary hypertension. 1

Why This Test Matters: Clinical Impact

Primary aldosteronism causes dramatically worse outcomes than primary hypertension at equivalent blood pressure levels 1:

• 3.7-fold increase in heart failure 1
• 4.2-fold increase in stroke 1
• 6.5-fold increase in myocardial infarction 1
• 12.1-fold increase in atrial fibrillation 1
• Increased left ventricular hypertrophy, diastolic dysfunction, arterial stiffness, tissue fibrosis, and kidney damage 1

Critically, these deleterious effects are often reversible with appropriate treatment (unilateral adrenalectomy or mineralocorticoid receptor antagonists), making early detection through ARR screening potentially life-saving. 1

Who Should Be Screened

Screen all patients with 1, 2:

• Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) - prevalence up to 20% 1
• Severe hypertension (BP >180/110 mmHg) 2
• Spontaneous or diuretic-induced hypokalemia 2
• Adrenal incidentaloma discovered on imaging 1, 2
• Early-onset hypertension or stroke at young age (<40 years) - suggests familial hyperaldosteronism 1, 2

How to Perform the Test Correctly

Patient Preparation

Potassium repletion is mandatory - hypokalemia suppresses aldosterone production and causes false-negative results. 1, 2 Target serum potassium 4.0-5.0 mEq/L before testing. 2

Medication management 1, 2:

• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing 2
• Stop beta-blockers, centrally acting drugs, and diuretics when clinically feasible (these suppress renin and cause false-positives) 1, 2
• Safe alternatives: long-acting calcium channel blockers and alpha-receptor antagonists minimally interfere with ARR 1, 2
• If medications cannot be stopped, proceed with testing and interpret results in context of specific medications 1, 3

Dietary preparation 1, 2:

• Unrestricted (liberal) salt intake before testing 1, 2

Blood Collection Technique

Timing and positioning are critical 1, 2:

• Collect blood in the morning (ideally 0800-1000 hours) 2
• Patient must be out of bed for at least 2 hours prior to collection 1, 2
• Patient seated for 5-15 minutes immediately before blood draw 1, 2

Interpreting Results

Positive Screening Test Criteria

A positive ARR requires BOTH 1, 2:

• ARR ≥20-30 (when aldosterone measured in ng/dL and renin activity in ng/mL/h) 1, 2
• Plasma aldosterone concentration ≥10-15 ng/dL 1, 2

The specificity improves if minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1, 2

Why Both Criteria Matter

The ARR can be falsely elevated simply from low renin (common in volume expansion, dietary salt excess, low-renin essential hypertension, chronic kidney disease). 1, 4 Requiring an elevated absolute aldosterone level prevents false-positives from these low-renin states. 1, 4

Next Steps After Positive Screening

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 1, 2

Confirmatory Test Options 1, 2:

1. Intravenous saline suppression test: Infuse 2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis 2
2. Oral sodium loading test: 24-hour urine aldosterone measurement after salt loading 1, 2
3. Fludrocortisone suppression test 2

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination (unilateral vs. bilateral disease) and treatment planning. 1, 2

Common Pitfalls to Avoid

Do not rely on hypokalemia as a screening trigger - it is absent in approximately 50% of primary aldosteronism cases. 1, 2 This is the most common reason for missed diagnoses.

Do not proceed to surgery based on CT findings alone - adrenal venous sampling is mandatory to distinguish unilateral from bilateral disease, as CT misses aldosterone-producing adenomas and demonstrates non-functioning nodules in up to 25% of cases. 2, 5

Do not dismiss the diagnosis in normotensive patients - recent evidence shows primary aldosteronism can be present in 11.3% of normotensive patients. 6

Do not delay testing due to inability to stop medications - the ARR can be performed while patients continue antihypertensive therapy, with results interpreted in context of specific medications. 1, 3 This is safer than risking uncontrolled hypertension from medication withdrawal.

Clinical Bottom Line

The ARR is not just another lab test - it identifies a common, dangerous, and potentially curable form of hypertension that causes substantially worse cardiovascular outcomes than primary hypertension. 1 With prevalence reaching 20% in resistant hypertension, systematic screening using ARR can offer diagnosis and curative treatment to thousands of patients who would otherwise suffer preventable cardiovascular complications. 1, 7