High Aldosterone/Renin Ratio with Decreased Renin Activity
What This Means
A high aldosterone/renin ratio (ARR) with decreased (suppressed) renin activity strongly suggests primary aldosteronism, a condition where the adrenal glands autonomously produce excessive aldosterone independent of normal regulatory mechanisms. 1
Understanding the Pathophysiology
Primary aldosteronism is characterized by autonomous aldosterone production that is relatively independent of angiotensin II and potassium regulation, leading to suppressed plasma renin activity. 1
The excessive aldosterone causes sodium retention and volume expansion, which physiologically suppresses renin production—this is why you see the low renin activity. 2
This autonomous aldosterone production causes hypertension, cardiovascular and kidney damage, and increased potassium excretion (though hypokalemia is absent in approximately 50% of cases). 1, 2
Interpreting Your Specific Results
A high ARR (typically >30 when aldosterone is measured in ng/dL and renin activity in ng/mL/h) with low renin suggests primary aldosteronism. 1
However, for a truly positive screening test, the plasma aldosterone concentration should be at least 10 ng/dL in addition to the elevated ratio—the ratio alone is insufficient. 1, 3
Low renin can artificially elevate the ARR even without truly elevated aldosterone levels, which is why the absolute aldosterone value matters. 1
The specificity of the ratio improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1
Alternative Causes of Low Renin to Consider
Before concluding this is primary aldosteronism, consider these differential diagnoses:
Low-renin essential hypertension (particularly common in Black patients) can produce similar laboratory findings. 1
Chronic kidney disease with reduced renin production. 1
Cushing syndrome, which can present with hypertension, hypokalemia, and suppressed renin. 1
Excessive sodium intake or volume expansion states can suppress renin physiologically. 1
Next Steps: Confirmatory Testing Required
A positive ARR screening test is NOT diagnostic by itself—confirmatory testing is mandatory to demonstrate autonomous aldosterone secretion. 3, 4
Patient Preparation for Confirmatory Testing:
Ensure unrestricted salt intake and normal serum potassium levels (hypokalemia suppresses aldosterone and causes false-negatives). 3
Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing. 1, 3
Discontinue beta-blockers, centrally acting drugs, and diuretics when clinically feasible (these suppress renin and cause false-positives). 3
Confirmatory Test Options:
Intravenous saline suppression test: Infuse 2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms the diagnosis. 3
Oral salt-loading test: Measure 24-hour urine aldosterone after sodium loading. 1, 3
After Confirmation: Subtype Determination
If primary aldosteronism is confirmed, adrenal venous sampling is recommended before surgical treatment to distinguish unilateral from bilateral disease—without it, 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone. 1
Treatment Depends on Subtype:
Unilateral disease (aldosterone-producing adenoma): Laparoscopic adrenalectomy is the treatment of choice, improving blood pressure in virtually 100% of patients and curing hypertension in approximately 50%. 1, 2
Bilateral adrenal hyperplasia: Medical treatment with mineralocorticoid receptor antagonists (spironolactone first-line, eplerenone as alternative) is the cornerstone of therapy. 1, 2
Critical Pitfalls to Avoid
Do not rely on the presence of hypokalemia to suspect or exclude primary aldosteronism—it is absent in the majority of cases. 1, 3
Do not proceed to surgery based on CT findings alone without adrenal venous sampling. 1
Do not interpret an elevated ARR as diagnostic without checking the absolute aldosterone level (must be ≥10 ng/dL). 1, 3
Do not perform testing while patients are on mineralocorticoid receptor antagonists—these must be withdrawn for at least 4 weeks. 1, 3
Clinical Significance
Primary aldosteronism is present in up to 20% of individuals with resistant hypertension, yet only approximately 2% of eligible patients get screened. 3, 4
Patients with primary aldosteronism have a 12-fold increased risk of target organ damage including kidney injury compared to primary hypertension, emphasizing the importance of early diagnosis and treatment. 2
The deleterious effects are often reversible with appropriate treatment (surgery or mineralocorticoid receptor antagonists), which can normalize hypokalemia, lower blood pressure, reduce medication requirements, and improve cardiac and kidney function. 1, 2