Which factors can affect the interpretation of aldosterone-to-renin ratio (ARR) results in the workup of hyperaldosteronism?

Updated: Oct 19, 2018
  • Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London); Chief Editor: Robert P Hoffman, MD  more...
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Answer

The most important factors that can interfere with the diagnostic reliability of the ARR test are drugs and renal impairment (Table below). [22, 25, 33] Beta blockers can reduce PRA, leading to a falsely elevated ARR, and dihydropyridine calcium antagonists (eg, nifedipine) can reduce aldosterone levels, potentially leading to a falsely normal ARR in some patients with primary hyperaldosteronism. Diuretics tend to induce secondary hyperaldosteronism. Spironolactone, an aldosterone receptor antagonist, can raise plasma renin levels.

Table 1. Factors affecting interpretation of ARR results (Open Table in a new window)

False Negative Results

Factor

Aldosterone

Renin

ARR

Medications

 

 

 

K-sparing diuretics

↑↑

K-wasting diuretics (Non-K-sparing diuretics, such as thiazides, induce renal potassium losses and reduce plasma potassium concentrations, leading to decreased aldosterone secretion.)

→↑

↑↑

ACE inhibitors

↑↑

Angiotensin receptor blockers

↑↑

DHPs (It is a shared opinion that dihydropyridinic calcium channel blockers do not significantly affect aldosterone secretion, mainly causing an increase in PRA, which rarely gives false negatives.)

→↓

Other conditions

Hypokalemia

→↑

Sodium-restricted diet

↑↑

Pregnancy

↑↑

Renovascular hypertension

↑↑

Malignant hypertension

↑↑

False Positive Results

Beta-adrenergic blockers

↓↓

Central alpha-2 agonists (eg, clonidine, alpha-methyldopa)

↓↓

NSAIDS

↓↓

Other conditions

Potassium loading

→↓

Sodium-loaded diet

↓↓

Advancing age

↓↓

Renal dysfunction

→↑

PHA-2

Luteal phase of menstrual cycle

PRA: Unchanged

Antihypertensive Medications With Minimal Effect on the ARR

Prazosin, doxazosin, terazosin

 

←→

Verapamil, hydralazine

 

←→

Other medications

Renin inhibitors (Renin inhibitors raise the ARR if renin is measured as PRA [false positive] and lower it if measured as DAR concentration [false negative.])

↑↓

↑↓

SSRIs

OCPs (OCPs have little effect on ARR when renin is measured as PRA. Use of immunometric measurements of DAR rather than PRA may give false positive results. Subdermal etonogestrel has no effect on ARR.)

↓DAR

Liddle syndrome

Normal

 

ARR, aldosterone-renin ratio; NSAIDs, non-steroidal anti-inflammatory drugs; K, potassium; ACE, angiotensin converting enzyme; ARBs, angiotensin II type 1 receptor blockers; DHPs, dihydropyridines; PHA-2, pseudohypoaldosteronism type 2; PRA, plasma renin activity; DAR, direct active renin; OCPs, oral contraceptive agents; SSRIs, selective serotonin reuptake inhibitors


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