Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS
The aldosterone/plasma renin activity ratio, measured by LC/MS/MS, screens for primary aldosteronism by detecting autonomous aldosterone secretion — an elevated aldosterone that persists despite suppressed renin. It is the first-line test in resistant or severe hypertension, hypertension with hypokalaemia, and patients with adrenal incidentaloma, interpreted under standardised conditions with…
3
Biomarkers
Blood (plasma)
Sample
5–7 business days
Turnaround
Recommended
Fasting
What is the Aldosterone/PRA Ratio test?
The Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS, is the first-line screening investigation for primary aldosteronism, a common yet under-diagnosed cause of secondary hypertension characterised by autonomous aldosterone secretion and suppressed renin. Practitioners order the ratio — rather than aldosterone or renin alone — because the physiological relationship between the two analytes is what reveals autonomy: an elevated aldosterone that persists despite low renin indicates that the adrenal zona glomerulosa is escaping normal feedback. Primary aldosteronism accounts for approximately 5–10 per cent of all hypertension and a higher proportion of resistant cases, yet it often goes unrecognised because hypokalaemia, once considered hallmark, is present in only a minority. The ratio therefore serves both to case-find in at-risk populations and to exclude the diagnosis in those with a compatible presentation. LC/MS/MS methodology offers improved analytical specificity over immunoassay, reducing interference from structurally related steroids and providing more reliable aldosterone quantitation, particularly at the low and high ends of the measurement range.
What does the Aldosterone/PRA Ratio test measure?
Aldosterone is a mineralocorticoid synthesised in the zona glomerulosa of the adrenal cortex under the control of the renin–angiotensin system, serum potassium, and adrenocorticotropic hormone. It regulates sodium reabsorption and potassium excretion in the distal nephron, thereby controlling blood volume and pressure. Secretion varies markedly with posture, sodium balance, and time of day, so sampling conditions must be standardised.
Plasma aldosterone concentration is the numerator of the aldosterone/renin ratio and the primary measure of mineralocorticoid output. Isolated aldosterone values are difficult to interpret without knowing renin status, because aldosterone should be suppressed when renin is low and stimulated when renin is high; inappropriate elevation in the setting of suppressed renin defines primary aldosteronism.
Plasma renin activity measures the rate of angiotensin I generation by circulating renin acting on its endogenous substrate angiotensinogen. It is regulated by renal perfusion pressure, sodium delivery to the distal tubule, and sympathetic tone. PRA declines with age and is sensitive to posture, sodium intake, and interfering medications.
PRA is the denominator of the ratio and reflects the integrity of the renin–angiotensin–aldosterone axis. Suppressed PRA with elevated aldosterone points to primary aldosteronism; high PRA with elevated aldosterone suggests secondary hyperaldosteronism (renovascular disease, volume depletion); low-renin hypertension without aldosterone excess may reflect a genetic or salt-sensitive phenotype.
The ratio is a derived marker that expresses aldosterone output relative to renin drive. Because aldosterone secretion should track with renin, an inappropriately high ratio — aldosterone that is not suppressed despite low renin — suggests autonomous aldosterone production independent of the renin–angiotensin axis.
The aldosterone/renin ratio is the best initial screening test for primary aldosteronism in patients with hypertension and hypokalaemia or resistant hypertension. A high ratio prompts confirmatory testing (saline suppression, oral sodium loading, or captopril challenge) and, if confirmed, imaging and possibly adrenal vein sampling to distinguish unilateral from bilateral disease.
Why is the Aldosterone/PRA Ratio test ordered?
- Investigation of resistant hypertension (blood pressure above goal despite three agents, one a diuretic) or severe hypertension (≥160/100 mmHg) at presentation
- Evaluation of hypertension with spontaneous or diuretic-induced hypokalaemia (serum potassium <3.5 mmol/L)
- Screening of hypertensive patients with an adrenal incidentaloma, which may represent an aldosterone-producing adenoma
- Work-up of early-onset hypertension (age <40 years) or a family history of primary aldosteronism or early cerebrovascular events
- Assessment of patients with obstructive sleep apnoea and hypertension, a phenotype associated with higher rates of primary aldosteronism
- Exclusion of mineralocorticoid excess in patients with low-renin hypertension when the clinical picture is equivocal
- Monitoring of the renin–aldosterone axis in patients with suspected secondary hyperaldosteronism (renal artery stenosis, volume depletion, heart failure)
Sample collection and turnaround
Sample type
Blood (plasma)
Fasting required
Recommended
Collection method
Venipuncture at patient service centre
Turnaround
5–7 business days
Collection notes
Phlebotomy via Quest. Draw in the morning after the patient has been upright (seated or ambulatory) for at least two hours, ideally fasting. Collect into EDTA or heparin plasma tube (verify Quest's preferred anticoagulant); separate plasma promptly and freeze if not analysed same-day. Document posture and time of draw. Ideally, withdraw interfering antihypertensives (particularly spironolactone, ACE inhibitors, ARBs, beta-blockers, direct renin inhibitors) for an adequate washout period under specialist guidance, substituting non-interfering agents as needed.
Specimen requirements
Minimum plasma volume per Quest protocol (typically 1–2 mL). Aldosterone and renin must be measured from the same draw. Freeze plasma at –20°C or below if shipment or analysis is delayed; avoid multiple freeze–thaw cycles.
What can affect Aldosterone/PRA Ratio results?
Mineralocorticoid antagonists (spironolactone, eplerenone) raise both aldosterone and renin and invalidate the ratio; renin–angiotensin system inhibitors raise renin and lower the ratio, potentially masking primary aldosteronism. Beta-blockers suppress renin and may elevate the ratio. Ideally withdraw interfering agents for an adequate washout (four to six weeks for spironolactone, two weeks for most others), substituting non-interfering agents such as verapamil, hydralazine, or alpha-blockers if blood pressure control permits.
Low sodium intake stimulates renin and aldosterone and can lower the ratio; high sodium suppresses renin more than aldosterone in primary aldosteronism, raising the ratio. Hypokalaemia directly stimulates aldosterone secretion. Ideally, patients should have liberal sodium intake and potassium repletion before testing.
Aldosterone and renin both rise with upright posture, but renin increases more, lowering the ratio. Sampling after at least two hours upright is recommended to standardise conditions; some protocols use morning, fasting, seated sampling. Inconsistent posture between serial tests reduces comparability.
Secondary hyperaldosteronism due to reduced renal perfusion or volume depletion raises both aldosterone and renin, typically with a normal or low ratio. Screening should be deferred until the patient is stable and euvolaemic.
Oestrogen raises angiotensinogen and can increase renin and aldosterone, potentially lowering the ratio. Some guidelines recommend testing during the follicular phase or after discontinuing oral contraceptives, though data are conflicting.
Chronic kidney disease may alter renin–aldosterone dynamics; PRA may be low due to reduced renin secretion or inappropriately normal despite volume expansion. The ratio remains interpretable, but thresholds and confirmatory testing require careful clinical correlation.
What do Aldosterone/PRA Ratio results mean?
Elevated
An aldosterone/renin ratio above the threshold (typically >20–30, assay-specific) with an aldosterone concentration above a minimum (often >10–15 ng/dL) is a positive screen for primary aldosteronism. This pattern — aldosterone that is not suppressed despite low renin — suggests autonomous secretion. A positive screen must be confirmed by a suppression test (saline infusion, oral sodium loading, or captopril challenge) before proceeding to subtype classification, because false positives occur. Very high ratios with marked aldosterone elevation and profound hypokalaemia make primary aldosteronism highly likely.
Normal
A ratio below the screening threshold, obtained under appropriate conditions (off interfering medications, adequate sodium and potassium, standardised posture), effectively excludes primary aldosteronism. Hypertension in this setting is unlikely to be aldosterone-driven, and other causes should be investigated.
Reduced
A low ratio (aldosterone suppressed relative to renin) or high renin with elevated aldosterone points to secondary hyperaldosteronism — renovascular hypertension, volume depletion, diuretic use, or heart failure. This pattern indicates that the renin–angiotensin axis is intact and appropriately driving aldosterone. Low-renin, low-aldosterone states may reflect chronic suppression or a salt-sensitive phenotype without mineralocorticoid excess.
Note: The ratio is exquisitely sensitive to medication, sodium balance, and sampling conditions; even a negative screen can be unreliable if interfering drugs were not withdrawn or the patient was volume-depleted. A borderline ratio or discordant clinical picture warrants repeat testing or proceeding directly to confirmatory suppression testing. The ratio is a screening tool, not a diagnosis — subtype differentiation (unilateral adenoma vs bilateral hyperplasia) requires imaging and often adrenal vein sampling, which guide whether surgery or medical therapy is appropriate.
Frequently asked questions
The ratio screens for primary aldosteronism, a common cause of secondary hypertension in which autonomous aldosterone secretion suppresses renin. An elevated ratio indicates that aldosterone is inappropriately high relative to renin drive and prompts confirmatory testing.
How to access the Aldosterone/PRA Ratio test
The Aldosterone/PRA Ratio reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.
Create Free AccountAbout this page
Published: October 7, 2026
Last reviewed: October 7, 2026
- Funder JW, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment — an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. (2016)
- Rossi GP, et al. Primary aldosteronism: JACC state-of-the-art review. J Am Coll Cardiol. (2019)
- Byrd JB, et al. Primary aldosteronism: practical approach to diagnosis and management. Circulation. (2018)
- Käyser SC, et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis. J Clin Endocrinol Metab. (2016)
This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.
Related tests
adrenal stress
Serum Cortisol
The Cortisol Serum test quantifies total circulating cortisol — bound and free fractions combined — providing the primary biochemical assessment of HPA axis function and adrenocortical output. Morning collection (07:00–09:00) is the standard for adrenal insufficiency screening — a value above 18–20 µg/dL effectively excludes adrenal insufficiency; below 3 µg/dL strongly confirms it;
metabolic diabetes
Serum Potassium
The Serum Potassium test quantifies extracellular potassium concentration — the dominant determinant of cardiac membrane potential and neuromuscular excitability — in serum. It is a mandatory monitoring parameter for diuretic therapy, ACE inhibitor and ARB use, CKD management, adrenal disease evaluation, and cardiac arrhythmia risk stratification.