How do you interpret renin and aldosterone levels in clinical practice?

Interpreting Renin and Aldosterone Levels in Clinical Practice

The aldosterone-to-renin ratio (ARR) is the recommended first-line screening test for primary aldosteronism, with interpretation requiring careful consideration of medications, sodium intake, and posture during testing. 1

Understanding Renin-Aldosterone Physiology

• Normal physiology: Renin is released from the juxtaglomerular cells in response to decreased renal perfusion, while aldosterone is produced by the adrenal glands in response to angiotensin II or high potassium levels
• Primary aldosteronism: Characterized by autonomous aldosterone production, typically with suppressed renin levels
• Prevalence: Affects 5-13% of all hypertensive patients and up to 50% of patients with resistant hypertension 1

Interpreting the Aldosterone-to-Renin Ratio (ARR)

ARR Calculation and Interpretation

• Positive ARR: ≥30 when plasma aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h, with plasma aldosterone at least 10 ng/dL 1
• Clinical significance: Seated aldosterone level >16 ng/dL without saline suppression is considered clinically significant 1
• Variability: ARR becomes increasingly variable as its mean value increases, with similar variability in both short-term and long-term measurements 2

Factors Affecting ARR Interpretation

Medication Effects

1. Medications that interfere with ARR testing 3:

   • Beta-blockers (increase ARR by suppressing renin)
   • Centrally acting drugs (e.g., clonidine, alpha-methyldopa)
   • Diuretics (decrease ARR)
   • Mineralocorticoid receptor antagonists (MRAs)

2. Medications with minimal interference 3, 4:

   • Long-acting calcium channel blockers (dihydropyridine or non-dihydropyridine)
   • Alpha-receptor antagonists
   • ACE inhibitors and AT1 receptor antagonists (minor effect)

Two Approaches to ARR Testing in Treated Patients 3

1. Test without changing medications:

   • Advantages: Reduces barriers to screening, maintains BP control
   • Disadvantages: Requires interpretation in context of medications
   • May need specialist input

2. Discontinue interfering medications:

   • Provides "clean" screening
   • Substitute with non-interfering medications when possible
   • Use centrally acting sympatholytics if necessary (slight risk of false positives)

Other Important Factors

• Sodium intake: Assess 24-hour urinary sodium or sodium-to-creatinine ratio 3
• Menstrual cycle in females 3
• Posture during testing: Standardize collection conditions 2
• Renal function: Hypertensive kidney damage can cause escape of renin from suppression 5

Clinical Scenarios and Interpretation

Primary Aldosteronism

• Classic pattern: High aldosterone, suppressed renin, elevated ARR
• Important note: Do not rule out primary aldosteronism based on normal potassium levels, as hypokalemia is present in only 9-37% of cases 1
• Atypical presentation: Some patients with severe hypertension due to primary aldosteronism may have non-suppressed renin due to hypertensive kidney damage 5

Low-Renin Hypertension

• Characterized by aldosterone <500 ng/dL and ARR ≥1,000 6
• Different from primary aldosteronism but may respond to similar treatments

Secondary Hyperaldosteronism

• High aldosterone (≥1,000 ng/dL) with normal/high renin (ARR <400) 6
• Causes include renovascular hypertension, diuretic use, heart failure

When to Screen for Primary Aldosteronism

Screen patients with 1:

• Resistant hypertension
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Hypertension with adrenal incidentaloma
• Early-onset hypertension or family history of early-onset hypertension
• Symptoms like muscle cramping, weakness, headaches, or intermittent paralysis

Confirmatory Testing and Next Steps

After positive ARR screening:

1. Confirmatory testing: Intravenous saline suppression test, oral salt loading test, or fludrocortisone suppression test 1
2. Imaging: Non-contrast CT scan of adrenal glands (MRI if CT contraindicated) 1
3. Adrenal venous sampling: Gold standard for distinguishing unilateral from bilateral disease 1

Common Pitfalls in Interpretation

• False positive ARR: Beta-blockers can cause false positives by suppressing renin 4
• False negative ARR: Irbesartan and other ARBs may cause false negatives (23.5% with irbesartan) 7
• Renal impairment: Can cause non-suppressed renin despite primary aldosteronism 5
• Variability in measurements: ARR has acceptable short-term variability in lower ranges but becomes less reliable as values rise 2