What is the utility of testing plasma renin activity and aldosterone in patients with hypertension?

Utility of Plasma Renin Activity and Aldosterone Testing in Hypertension

The plasma aldosterone:renin activity ratio is the most accurate and reliable screening test for primary aldosteronism in patients with hypertension, particularly those with resistant hypertension, hypokalemia, incidentally discovered adrenal masses, family history of early-onset hypertension, or stroke at a young age. 1

When to Screen for Primary Aldosteronism

Primary aldosteronism screening should be performed in patients with:

• Resistant hypertension (occurs in up to 20% of these patients)
• Hypokalemia (spontaneous or substantial if diuretic-induced)
• Incidentally discovered adrenal masses
• Family history of early-onset hypertension
• Stroke at a young age (<40 years)
• Hypertension with increased target organ damage compared to expected for BP level 1

Primary aldosteronism is one of the most common causes of secondary hypertension, occurring in 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension. It causes greater target organ damage than primary hypertension, including:

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

How to Perform the Aldosterone:Renin Activity Ratio Test

1. Collection timing: Morning blood samples are preferred

2. Patient preparation:

   • Unrestricted salt intake
   • Normal serum potassium levels
   • Withdrawal of mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks 1
   • Other antihypertensive medications can generally be continued during screening 2

3. Interpretation:

   • Most commonly used cutoff value is 30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h
   • A ratio ≥30 has >80% specificity and 100% sensitivity; a ratio ≥100 has 99% specificity 1, 3
   • Plasma aldosterone concentration should be at least 10 ng/dL to interpret the test as positive 1
   • Low renin levels can influence the ratio, so some experts suggest a minimum plasma renin activity of 0.5 ng/mL/h for calculation 1

Diagnostic Algorithm After Positive Screening

1. Confirmatory testing: If screening is positive, confirmatory testing is required (intravenous saline suppression test or oral salt-loading test) 1

2. Referral: Patients with confirmed primary aldosteronism should be referred to a hypertension specialist or endocrinologist for further evaluation and treatment 1

3. Subtype determination:

   • Adrenal imaging (CT or MRI)
   • Adrenal venous sampling to determine if aldosterone production is unilateral or bilateral 1

4. Treatment options:

   • Unilateral aldosterone production: Laparoscopic adrenalectomy (improves BP in virtually 100% of patients and cures hypertension in about 50%)
   • Bilateral aldosterone production: Medical therapy with mineralocorticoid receptor antagonists (spironolactone or eplerenone) 1

Clinical Pearls and Pitfalls

• Common misconception: Primary aldosteronism only occurs with hypokalemia. In reality, hypokalemia is absent in the majority of cases 1

• Testing convenience: The aldosterone:renin ratio can be measured without discontinuing most antihypertensive medications, making it a practical screening tool 2

• Alternative testing: Direct renin concentration (DRC) can be used instead of plasma renin activity, with the aldosterone/direct renin concentration ratio (ADRR) showing good correlation with the traditional ARR 3

• Treatment benefits: Both surgical and medical treatments are effective in lowering BP and reversing left ventricular hypertrophy, making screening and diagnosis worthwhile for improving outcomes 1

By identifying and properly treating primary aldosteronism, clinicians can significantly reduce morbidity and mortality associated with this common but often overlooked cause of hypertension.