PharmacologyTier 1Medical Sciences concept

Drug interference with aldosterone-renin ratio testing

Core concept

Aldosterone-renin ratio (ARR) is the screening test for primary hyperaldosteronism -- many common antihypertensives distort renin and/or aldosterone, causing false positive/negative results
General principle: drugs that suppress renin (beta-blockers) risk false positive ARR; drugs that raise renin (diuretics, ACEi/ARB, dihydropyridine CCB) risk false negative ARR (by lowering the ratio)
Spironolactone/eplerenone (MR antagonists) invalidate the test outright -- must be stopped well in advance

Drug class	Effect on renin	Effect on ARR
Beta-blockers	dec renin	False positive (ratio falsely high)
Diuretics (incl. spironolactone)	inc renin	False negative
ACEi/ARB	inc renin	False negative
Dihydropyridine CCB	inc renin (mild)	False negative (mild)
Alpha-blockers, verapamil, hydralazine	Minimal effect	Preferred agents for BP control during testing

Where possible, withdraw interfering drugs 2-6 weeks before testing (spironolactone/eplerenone specifically need ~6 weeks) and substitute with agents that have minimal ARR effect (verapamil slow-release, hydralazine, prazosin) to maintain BP control
Trap: testing "on treatment" without correction can both miss true primary hyperaldosteronism (false negative on ACEi/diuretic) and falsely suggest it (false positive on beta-blocker) -- always interpret ARR against current medications
If drugs cannot safely be stopped (e.g. severe hypertension), interpret ARR with caution and favour confirmatory testing over the ratio alone

Same renin-suppression principle explains why NSAIDs (sodium retention, dec renin) can also distort the ratio
Confirmatory testing (saline suppression, fludrocortisone suppression, captopril challenge) is used once ARR screens positive -- has its own separate interference profile
Relates to the broader theme of secondary hypertension screening requiring medication washout (e.g. also relevant to catecholamine/metanephrine testing with interfering drugs)

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