When to Order Aldosterone-to-Renin Ratio in Treatment-Resistant Hypertension
You should order an aldosterone-to-renin ratio (ARR) now in any patient with hypertension not responding to an ACEI and HCTZ, as this defines resistant hypertension and primary aldosteronism affects up to 20% of this population. 1
Immediate Screening Indication
Your patient meets the definition of resistant hypertension—blood pressure remaining uncontrolled despite optimal doses of multiple antihypertensive medications including a diuretic. 1 This alone is sufficient indication for ARR screening, regardless of whether other features like hypokalemia are present. 1
Why Screen Now
- Primary aldosteronism is present in up to 20% of patients with resistant hypertension, making it the most common identifiable cause of secondary hypertension in this population. 1
- Patients with primary aldosteronism have dramatically worse cardiovascular outcomes than those with essential hypertension at equivalent blood pressure levels, including 3.7-fold increased heart failure, 4.2-fold increased stroke, and 12.1-fold increased atrial fibrillation. 1
- Early detection and treatment prevents irreversible target organ damage and can potentially cure hypertension in 30-60% of cases with unilateral disease. 1, 2
Practical Testing Approach
Test Without Stopping Current Medications
You can and should order the ARR while the patient continues taking ACEI and HCTZ. 3 While these medications interfere with the test by raising renin levels (causing false-negative results), stopping them is often dangerous in patients with poorly controlled hypertension. 4, 5
- ACE inhibitors and diuretics both increase renin levels, which lowers the ARR and can cause false-negative results. 4
- However, testing on current medications is acceptable—interpret results in context of known drug effects. 1, 5
- A study of 90 patients with poorly controlled hypertension found that ARR screening without discontinuing medications successfully identified all cases of primary aldosteronism without false positives. 3
Optimal Testing Protocol
- Collect blood in the morning (ideally 0800-1000 hours) with the patient seated for 5-15 minutes before the blood draw. 1
- Ensure the patient is potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 1
- A positive screening test requires both ARR ≥20-30 ng/dL per ng/mL/hr and plasma aldosterone concentration ≥10-15 ng/dL. 1
Critical Pitfall to Avoid
Do not wait for hypokalemia to develop before ordering the ARR. 1 Hypokalemia is absent in approximately 50% of primary aldosteronism cases, and relying on its presence will miss half of all cases. 1 The combination of resistant hypertension alone justifies screening.
Immediate Management While Awaiting Results
Consider adding spironolactone 25-50 mg daily immediately after ordering the ARR, even before confirmatory testing is completed. 1 This provides significant additional blood pressure reduction of 25/12 mmHg when added to multidrug regimens in resistant hypertension, regardless of whether primary aldosteronism is ultimately confirmed. 1
- Monitor serum potassium within 1 week of starting spironolactone, as hyperkalemia risk is increased with concurrent ACEI use. 1
- Low doses (25-50 mg daily) are effective and minimize adverse effects. 1
Next Steps After Positive Screening
- All positive ARR screening tests require confirmatory testing (intravenous saline suppression test or oral sodium loading with 24-hour urine aldosterone) to demonstrate autonomous aldosterone secretion. 1
- Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination via adrenal venous sampling. 1
- Unilateral disease is treated with laparoscopic adrenalectomy (cures hypertension in ~50% and improves it in virtually 100%), while bilateral disease requires lifelong mineralocorticoid receptor antagonist therapy. 1, 2