How to check aldosterone plasma and plasma renin activity?

How to Check Aldosterone Plasma and Plasma Renin Activity

The preferred method for checking aldosterone and renin is the aldosterone/renin ratio (ARR), which should be performed in the morning after the patient has been out of bed for 2 hours and seated for 5-15 minutes, with the patient being potassium-replete and off interfering medications when possible. 1

Patient Preparation

• Patients should be potassium-replete before testing, as hypokalemia can suppress aldosterone production 1, 2
• Ideally, interfering medications should be substituted or discontinued when clinically appropriate 1
  • Beta-blockers, centrally acting drugs, and diuretics should be stopped when feasible 2
  • Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they minimally interfere with ARR 2
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking 2

Timing and Collection

• Collect blood in the morning (optimal time) 1
• Patient should be out of bed for 2 hours prior to collection 1
• Patient should be seated for 5-15 minutes immediately before collection 1
• Blood should be drawn with the patient in a seated position 1, 2

Test Interpretation

• An aldosterone/renin ratio (ARR) of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1
• For a positive ARR test, plasma aldosterone concentration should be at least 10-15 ng/dL in addition to the elevated ratio 1, 2
• The specificity of the ratio improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1, 2
• Low renin can artificially elevate the ARR even without truly elevated aldosterone levels 2

Considerations for Direct Renin Concentration vs Renin Activity

• Plasma renin concentration (PRC) measurements are increasingly replacing plasma renin activity (PRA) as they are faster, simpler, and more reproducible 3, 4
• When using direct renin concentration instead of plasma renin activity, different cutoff values must be used 4, 5
• A cutoff value of approximately 3.7 for the aldosterone/direct renin concentration ratio (ADRR) has been suggested as equivalent to an ARR of 30 3

Confirmatory Testing

• A positive screening test requires confirmation with additional testing 1, 2
• Confirmatory tests include:
  • Oral sodium loading with 24-hour urine aldosterone measurement 1
  • Saline suppression test (IV saline infusion with plasma aldosterone measurement at 4 hours) 1, 2
• Testing should be performed with unrestricted salt intake and normal serum potassium levels 2
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) should be withdrawn at least 4 weeks before testing 2

Common Pitfalls to Avoid

• Not accounting for medication effects on the ARR (particularly ACE inhibitors and ARBs which can lower the ratio) 6
• Failing to recognize that hypokalemia is absent in the majority of primary aldosteronism cases and has a low negative predictive value 1
• Using inappropriate cutoff values when switching between PRA and PRC methods 3, 4, 7
• Not considering poor reproducibility of ARR measurements (up to five-fold difference in values taken under the same conditions) 6
• Relying solely on ARR without considering the absolute aldosterone value 2

By following these guidelines, clinicians can appropriately screen for primary aldosteronism, which is present in up to 20% of individuals with resistant hypertension 1.