What does the plasma aldosterone-renin ratio show?

What the Plasma Aldosterone-Renin Ratio Shows

The plasma aldosterone-to-renin ratio (ARR) is a screening test that identifies patients with primary aldosteronism by detecting inappropriately high aldosterone production relative to suppressed renin activity. 1

Primary Purpose and Interpretation

The ARR serves as the initial screening tool to detect autonomous aldosterone secretion that characterizes primary aldosteronism, a condition present in up to 20% of patients with resistant hypertension. 1

Key diagnostic thresholds:

• A positive screening result is defined as ARR ≥30 (when aldosterone is measured in ng/dL and renin activity in ng/mL/h) AND plasma aldosterone concentration ≥10-15 ng/dL. 1
• The specificity improves when a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1
• An ARR of 20 ng/dL per ng/mL/hr demonstrates excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism. 1

Clinical Significance of Test Results

High ARR with Low Renin

This pattern suggests primary aldosteronism, where excessive aldosterone causes sodium retention and volume expansion, which physiologically suppresses renin production. 2 However, low renin can artificially elevate the ARR even without truly elevated aldosterone levels, which is why the absolute aldosterone value must also be elevated (≥10-15 ng/dL). 2

Differential diagnosis of low renin includes: 2

• Primary aldosteronism (most concerning)
• Low-renin essential hypertension (particularly common in Black patients)
• Chronic kidney disease with reduced renin production
• Cushing syndrome
• Excessive sodium intake or volume expansion

High ARR with Elevated Renin

When both aldosterone and renin are elevated, this indicates secondary hyperaldosteronism rather than primary aldosteronism. 3 The most common cause is renovascular hypertension from renal artery stenosis, where reduced renal perfusion stimulates renin release, which then drives aldosterone production. 3

Patient Preparation Requirements

Critical preparation steps to ensure accurate results: 1

• Patients must be potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results
• Blood should be collected in the morning with the patient out of bed for 2 hours and seated for 5-15 minutes immediately before collection
• Testing should be performed with unrestricted salt intake

Medication considerations: 1

• Beta-blockers, centrally acting drugs, and diuretics should be stopped when feasible (these suppress renin and cause false-positive results)
• Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they minimally interfere with ARR
• Mineralocorticoid receptor antagonists must be withdrawn at least 4 weeks before testing
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking

Who Should Be Screened

The ARR should be obtained in patients with: 1

• Resistant hypertension (BP not controlled on 3 medications including a diuretic)
• Severe hypertension (BP >180/110 mmHg)
• Hypertension with hypokalemia (spontaneous or diuretic-induced)
• Adrenal incidentaloma with hypertension
• Family history of early-onset hypertension or stroke at age <40 years

Confirmatory Testing Required

A positive ARR screening test always requires confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed. 1 The ARR alone is insufficient for diagnosis because it has only fair diagnostic accuracy, with sensitivity ranging from 73-87% and specificity of 74-75%. 4

Confirmatory test options include: 1

• Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis)
• Oral sodium loading with 24-hour urine aldosterone measurement
• Fludrocortisone suppression test

Common Pitfalls to Avoid

Do not rely on hypokalemia as a screening trigger - it is absent in approximately 50% of primary aldosteronism cases. 1 Normal potassium does not exclude the diagnosis. 1

Do not proceed to treatment based on ARR alone - confirmatory testing is mandatory because the ARR has limited diagnostic accuracy and can be affected by multiple factors including medications, dietary sodium, and volume status. 4

Do not skip adrenal venous sampling before surgery - CT findings alone lead to inappropriate surgery in 25% of cases, as adenomas on imaging can represent hyperplasia and nodular hyperplasia is common. 1, 3