Aldosterone : Renin ratio
Primary aldosteronism (PA) is associated with a higher risk of cardiovascular morbidity and mortality than patients with similar age, sex, and blood pressure who do not have PA.
Treating PA with:
- Unilateral adrenalectomy (for suitable unilateral disease), or
- Mineralocorticoid receptor antagonists (e.g., Spironolactone or Eplerenone)
Clinical Presentation
- Hypertension is often the only sign of primary aldosteronism.
- Hypokalaemia is absent in most patients, so normal potassium does not exclude the diagnosis.
Why ARR Is Important
Hypokalaemia can suppress aldosterone secretion, causing a false-negative ARR, so potassium should be measured and corrected if low.
Some patients with PA have normal aldosterone levels, but an inappropriately low renin level, resulting in an elevated ARR.
Screening Test : ARR
- Best performed before antihypertensive therapy is started, if possible.
- Requirements:
- Patient should be unfasted.
- Patient should have been ambulatory for at least 2 hours before blood collection.
- Measure:
- Plasma aldosterone
- Renin (direct renin concentration or plasma renin activity)
- Serum potassium
- interpretation:
- Renin suppressed/low
- Aldosterone inappropriately normal or high
- Therefore ARR elevated
Do not interpret the ratio alone. Always look at:
- Aldosterone level
- Renin level
- Potassium
- Sodium status
- Current medications
- Renal function
- Posture/time of collection
- Lab units and local cut-off values
AJGP suggests switching to less-interfering agents and performing ARR after about 6 weeks under stable conditions, especially with potassium corrected.
Pre-test checklist
1. Correct hypokalaemia first
Hypokalaemia can suppress aldosterone secretion, giving a false negative ARR.
Aim for:
- Potassium in normal range
- RACGP article suggests maintaining K⁺ around 4–5 mmol/L during preparation where possible.
Important point:
A patient with hypertension + hypokalaemia is already highly suspicious for primary aldosteronism, but many patients with PA are normokalaemic.
2. Do not salt restrict before testing
Low sodium intake increases renin and may reduce ARR, causing a false negative.
Advise:
- Normal dietary salt intake before testing
- Avoid deliberate salt restriction before ARR
3. Avoid volume depletion
Volume depletion increases renin and can lower ARR.
Watch for:
- Recent vomiting/diarrhoea
- Over-diuresis
- Dehydration
- Very low-carb/rapid weight-loss diets
- Excessive sweating/exercise
4. Morning collection and posture matter
ARR is affected by circadian rhythm and posture.
Usual approach:
- Morning blood test
- Patient ambulant/upright before collection depending on local lab protocol
- Seated for a short period before sampling if requested by the lab
- Use the same pathology provider’s collection instructions where possible
5. Pregnancy and menstrual cycle
In pregnancy, renin often rises substantially, which can make ARR falsely low.
In premenopausal women:
- Aldosterone may rise in the luteal phase
- Follicular phase testing is often preferred when practical
6. Renal impairment and age
Renal impairment can affect renin and aldosterone interpretation.
Watch for:
- CKD
- Older age, especially >65 years
- Low-renin states
- Higher false-positive risk if renin is very suppressed for reasons other than PA
7. NSAIDs
NSAIDs can suppress renin and may cause a false positive ARR.
Ask specifically about:
- Ibuprofen
- Naproxen
- Diclofenac
- Celecoxib
- OTC “anti-inflammatory” use
Medication effects on ARR
| Medication class | Aldosterone | Renin | ARR effect | Main risk |
|---|---|---|---|---|
| Beta blockers | ↓ | ↓↓ | ↑ | False positive |
| Central alpha-2 agonists, e.g. clonidine, methyldopa | ↓ | ↓↓ | ↑ | False positive |
| NSAIDs | variable | ↓ | ↑ | False positive |
| Spironolactone/eplerenone | ↑ | ↑↑ | ↓ | False negative |
| Amiloride/triamterene | ↑/variable | ↑↑ | ↓ | False negative |
| Thiazide/loop diuretics | →/↑ | ↑↑ | ↓ | False negative |
| ACE inhibitors | ↓ | ↑↑ | ↓ | False negative |
| ARBs | ↓ | ↑↑ | ↓ | False negative |
| Dihydropyridine CCBs, e.g. amlodipine/nifedipine | →/↓ | ↑ | ↓ | False negative |
| Direct renin inhibitor, e.g. aliskiren | variable | assay-dependent | unreliable | Difficult interpretation |
RACGP notes that replacing interfering drugs with sustained-release verapamil, prazosin, moxonidine and/or hydralazine reduces false positives and false negatives. Australian Prescriber similarly states that if interfering antihypertensives cannot be stopped, ARR interpretation must account for the medications and specialist advice may be needed.
Which medications to stop before ARR
Where safe, switch interfering antihypertensives to non-interfering or minimally interfering options, then check ARR after the patient has been stable for about 6 weeks. This is the RACGP/AJGP primary care approach.
Stop for at least 4 weeks, sometimes longer
| Stop | Reason |
|---|---|
| Spironolactone | Strong false negative risk |
| Eplerenone | Strong false negative risk |
| Amiloride | Strong false negative risk |
| Triamterene | Strong false negative risk |
| Thiazide diuretics | Raises renin, false negative risk |
| Loop diuretics | Raises renin, false negative risk |
Practical note:
If the patient is already on spironolactone/eplerenone/amiloride because PA is strongly suspected, stopping may cause significant hypertension or hypokalaemia. Do not stop in unstable patients without specialist input.
Stop for at least 2 weeks if clinically safe
| Stop/replace | Reason |
|---|---|
| Beta blockers | Suppress renin → false positive ARR |
| Clonidine/methyldopa | Suppress renin → false positive ARR |
| ACE inhibitors | Raise renin → false negative ARR |
| ARBs | Raise renin → false negative ARR |
| Dihydropyridine CCBs, e.g. amlodipine | Can lower ARR → false negative risk |
| NSAIDs | Suppress renin → false positive ARR |
Replacement antihypertensives during washout
Preferred options that interfere less with ARR:
Drugs that do not interfere with calculating the aldosterone:renin ratio5
| Starting dose | Maximum dose | |
| Sustained-release verapamil* | 180 mg daily | 240 mg daily |
| Moxonidine | 200 micrograms once at night | 200 micrograms twice daily after two weeks |
| Prazosin | 0.5 mg twice daily | 5 mg three times a day |
| Hydralazine hydrochloride | 12.5 mg twice daily | 50 mg three times a day |
* Administration of verapamil as two divided doses may provide better coverage over 24 hours, if necessary. Doses higher than 240 mg daily may be used, but are often limited by adverse effects, therefore addition of a second drug is advised before increasing the verapamil dose.
False positive vs false negative
False positive ARR
ARR appears high, but patient may not have PA.
Common causes:
- Beta blocker
- Clonidine/methyldopa
- NSAIDs
- Older age/low-renin hypertension
- CKD/low renin state
- Very low renin due to non-PA causes
Pattern:
- Renin very low
- Aldosterone not convincingly elevated
- ARR elevated mainly because denominator is tiny
False negative ARR
ARR appears normal/low, but patient may have PA.
Common causes:
- Spironolactone/eplerenone
- Amiloride/triamterene
- Thiazide or loop diuretic
- ACE inhibitor
- ARB
- Dihydropyridine CCB
- Low sodium diet
- Hypokalaemia
- Pregnancy
- Volume depletion
Pattern:
- Renin not suppressed because medication/diet/volume status has stimulated renin
- ARR becomes lower than expected
Practical note
ARR preparation
- Confirm indication for PA screening:
- Resistant hypertension
- Hypertension with hypokalaemia
- Severe hypertension
- Early-onset hypertension
- Hypertension with adrenal incidentaloma
- Hypertension with OSA
- Family history of early stroke/PA
- Check:
- UEC/eGFR
- Potassium
- Sodium
- Current antihypertensives
- NSAID use
- Pregnancy possibility if relevant
- Correct hypokalaemia before testing.
- Advise normal salt intake.
- Avoid dehydration/volume depletion.
- Avoid NSAIDs if possible.
- If safe, switch interfering BP medications to:
- Verapamil SR
- Prazosin
- Hydralazine
- Moxonidine
- Wait approximately 6 weeks after switching if following RACGP/AJGP approach.
- Request:
- Plasma aldosterone
- Direct renin concentration or plasma renin activity
- ARR
- UEC at same time
- Interpret with absolute aldosterone and renin values, not ARR alone.
Important safety note
Do not stop antihypertensives blindly in patients with:
- Severe hypertension
- Recent stroke/TIA
- Heart failure
- Advanced CKD
- Significant hypokalaemia
- High cardiovascular risk
- Frailty
- Pregnancy
In those cases, either interpret ARR on current medications with caution or discuss with endocrinology/hypertension clinic.
Key reference sources
RACGP / AJGP — “Screening for primary aldosteronism”, 2020
This is the most useful Australian GP-facing source. It states that ARR screening is ideally done before antihypertensives are started, and if the patient is already treated, commonly used medications can be replaced with sustained-release verapamil, prazosin, moxonidine and/or hydralazine. It also notes accuracy is improved by normokalaemia, and screening should be performed six weeks after these conditions are met.
Australian Prescriber — “Approach to the diagnosis of secondary hypertension in adults”, 2021
Good source for the broader secondary hypertension workup. It states that ARR should be interpreted with the absolute aldosterone and renin values, not the ratio alone, and that thresholds vary by laboratory assay. It also notes testing is most straightforward before antihypertensives are started, and if medications cannot be stopped, results must be interpreted in that context.
Australian Prescriber correction, 2022
Important because there was a correction to the ARR medication-effect table: potassium-wasting diuretics lower ARR, causing potential false negative results.
Endocrine Society of Australia — Medication switching to test for primary aldosteronism
Australian endocrine resource explaining that PA is suspected when aldosterone is normal/high with low or suppressed renin, producing an elevated ARR, and that many antihypertensives alter aldosterone and renin levels.