High Aldosterone to Plasma Renin Ratio
A high aldosterone-to-renin ratio (ARR) indicates autonomous aldosterone production, most commonly from primary aldosteronism, which requires confirmatory testing and subspecialty referral for further evaluation. 1
What the Test Indicates
An elevated ARR (≥30 when aldosterone is measured in ng/dL and renin activity in ng/mL/h) suggests inappropriate aldosterone secretion that is relatively independent of renin-angiotensin system regulation. 1
The high ratio reflects aldosterone production that cannot be suppressed by sodium loading and is autonomous from the normal regulators (angiotensin II and potassium). 1
For a truly positive screening test, the plasma aldosterone concentration must also be at least 10-15 ng/dL in addition to the elevated ratio—the ratio alone is insufficient. 1, 2
Clinical Significance
Primary aldosteronism is the underlying diagnosis in the majority of cases with elevated ARR and affects:
- Up to 20% of patients with resistant hypertension 2
- Approximately 6-13% of all hypertensive patients 3, 4
- Only about 2-4% of eligible high-risk patients actually get screened, representing significant underdiagnosis 2
Pathophysiology Behind the Ratio
In primary aldosteronism, excessive aldosterone causes sodium retention and mild volume expansion, which physiologically suppresses renin activity, creating the characteristic high aldosterone-to-low renin pattern. 1
The aldosterone excess leads to hypertension, cardiovascular and kidney damage, and increased potassium excretion (though hypokalemia is absent in approximately 50% of cases). 1
Important Caveats and Pitfalls
Atypical presentations exist where renin is NOT suppressed:
In patients with severe hypertension and secondary kidney damage from longstanding primary aldosteronism, renin can "escape" suppression and be normal or even elevated. 5
Despite non-suppressed renin, the ARR remains elevated because aldosterone is disproportionately high relative to renin. 5
These patients often have elevated serum creatinine and may develop severe hyperkalemia when treated with mineralocorticoid receptor antagonists due to decreased renal function. 5
Next Steps After a Positive Screening Test
Confirmatory testing is mandatory before proceeding with further workup:
Options include oral sodium loading test with 24-hour urine aldosterone measurement or intravenous saline suppression test (2L normal saline over 4 hours, with failure to suppress aldosterone below 5 ng/dL confirming diagnosis). 1, 2
Testing must be performed with unrestricted salt intake, normal serum potassium levels, and mineralocorticoid receptor antagonists withdrawn for at least 4 weeks. 1
After biochemical confirmation, referral to a hypertension specialist or endocrinologist is recommended for subtype determination (unilateral vs. bilateral disease) using adrenal CT imaging and adrenal venous sampling before determining treatment approach. 1, 2
Treatment Implications
Approximately 50% of cases are unilateral (aldosterone-producing adenoma or unilateral hyperplasia), which are treated with laparoscopic adrenalectomy, curing hypertension in about 50% and improving blood pressure in virtually 100%. 1
The remaining 50% have bilateral adrenal hyperplasia and require lifelong medical therapy with mineralocorticoid receptor antagonists (spironolactone or eplerenone). 1