When is it recommended to check renin levels?

Indications for Renin Testing in Hypertension Management

Renin testing is primarily recommended for screening for primary aldosteronism, which should be considered in all adults with confirmed hypertension (BP ≥140/90 mmHg), particularly in those with resistant hypertension, hypokalemia, adrenal masses, or family history of early-onset hypertension. 1

Primary Indications for Renin Testing

Screening for Primary Aldosteronism

• Renin is measured alongside aldosterone to calculate the aldosterone-renin ratio (ARR), which is the recommended screening test for primary aldosteronism 1
• The 2024 ESC guidelines recommend screening for primary aldosteronism by measuring renin and aldosterone in all adults with confirmed hypertension (BP ≥140/90 mmHg) 1
• Specific populations where testing is strongly indicated:
  • Patients with resistant hypertension (uncontrolled BP despite ≥3 medications) 1
  • Hypertension with spontaneous or diuretic-induced hypokalemia 1
  • Patients with incidentally discovered adrenal masses 1
  • Family history of early-onset hypertension or stroke at young age 1

Clinical Value of the Aldosterone-Renin Ratio (ARR)

• The ARR is more sensitive than measuring potassium levels alone, as up to 71% of patients with primary aldosteronism are normokalaemic 2
• An elevated ARR (typically >30 when aldosterone is in ng/dL and renin activity in ng/mL/h) with aldosterone level ≥10 ng/dL suggests primary aldosteronism 1
• Primary aldosteronism is present in up to 20% of individuals with resistant hypertension 1

Practical Aspects of Renin Testing

Testing Protocol

• Patients should have unrestricted salt intake and normal serum potassium levels before testing 1
• Mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone) should be withdrawn for at least 4 weeks before testing 1
• Other antihypertensive medications can often be continued during screening, making this test more practical in clinical settings 3
• A positive screening test should be followed by confirmatory testing (e.g., saline suppression test) 1

Interpretation Considerations

• Low renin with elevated aldosterone suggests primary aldosteronism
• Low renin with normal aldosterone may indicate low-renin hypertension
• Elevated renin with elevated aldosterone suggests secondary hyperaldosteronism
• The ARR can be influenced by very low renin levels, so plasma aldosterone should be at least 10 ng/dL to interpret a high ratio as positive 1

Clinical Impact of Renin Testing

Benefits of Early Detection

• Identifying primary aldosteronism allows for targeted therapy (surgical or medical) that can significantly improve blood pressure control 2, 4
• Patients with primary aldosteronism have higher rates of target organ damage compared to essential hypertension patients with similar BP levels 2
• Treatment with mineralocorticoid receptor antagonists (spironolactone or eplerenone) is particularly effective in patients with biochemical primary aldosteronism 2

Potential Pitfalls

• Certain medications can affect renin and aldosterone levels:
  • Beta-blockers and central alpha-2 agonists can suppress renin
  • Diuretics, ACE inhibitors, and ARBs can increase renin
  • Potassium status significantly affects aldosterone secretion
• Inadequate preparation (not normalizing potassium, continuing interfering medications) can lead to false results
• Interpretation requires consideration of concurrent medications and clinical context

Emerging Applications

• Low renin in the presence of renin-angiotensin system inhibitors (ACE inhibitors or ARBs) strongly suggests autonomous aldosterone secretion and may serve as an on-medication screening approach 5
• This "RAS-challenge" approach may be particularly useful in patients with treatment-resistant hypertension 5

Renin testing plays a crucial role in the diagnostic algorithm for hypertension, particularly for identifying primary aldosteronism, which is the most common potentially curable cause of hypertension. Early detection and appropriate management can significantly reduce cardiovascular morbidity and mortality associated with this condition.