Plasma Renin Activity With Reflex to Aldosterone
Plasma Renin Activity With Reflex to Aldosterone
This test is used to screen for primary aldosteronism.
Test Summary
Plasma Renin Activity With Reflex to Aldosterone
Test Code: 13817
Clinical use
- Screen for primary aldosteronism (PA)
Clinical background
PA is a treatable condition caused by one or both adrenal glands producing excess aldosterone, which can lead to hypertension, suppression of plasma renin, and low potassium levels. Patients with PA are at higher risk of cardiometabolic complications (eg, heart attack, heart failure, stroke, type 2 diabetes, atrial fibrillation).1 PA prevalence estimates range from 3% to 13% in the general population,2 up to 22% among patients with grade I through III hypertension, and up to 29% among those with resistant hypertension.3 Despite the high prevalence, screening rates for PA are extremely low and PA remains underdiagnosed, depriving patents of beneficial treatment, leading to suboptimal management, and exposing them to higher cardiovascular risk.3
The 2025 Endocrine Society guidelines on PA suggest that all patients with hypertension be screened for PA.3 Screening involves measuring both the plasma aldosterone concentration (PAC) and either direct renin concentration or plasma renin activity (PRA). In most circumstances, a positive screen is indicated by both (1) renin or PRA being low or suppressed and aldosterone levels being inappropriately high and (2) an elevated aldosterone-to-renin ratio (ARR).3 The guidelines also emphasize that screening results should be interpreted only after considering the methodology used for the test (eg, immunoassay or mass spectrometry), interfering medications (eg, mineralocorticoid receptor antagonists [MRAs]), and concurrent conditions (eg, hypokalemia, pregnancy, older age, heart or renal failure).3
Quest Diagnostics offers the Plasma Renin Activity Reflex to Aldosterone test (test code 13817), which is mass spectrometry-based testing that is consistent with guidelines for PA screening (measurement of direct renin concentration is not offered).3 Testing begins with measuring and reporting PRA; if PRA is ≤1.00 ng/mL/h, the patient’s PAC levels are measured and reported. According to the guidelines, the PRA and PAC results for these patients, combined with the calculated ARR, determine whether PA is likely (see Interpretive information and the Figure3–5 for details).3 PRA was chosen as the initial test based on a 2024 study that found that initial screening based on a PRA, rather than ARR, more efficiently identified patients with likely PA.4
The components of this reflex test can be ordered separately: Plasma Renin Activity (PRA), LC/MS/MS test (test code 16846), Aldosterone, LC/MS/MS test (test code 17181), and Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS (test code 16845). Reflex testing is performed at an additional charge with an additional CPT code.
Individuals suitable for testing
- Individuals >16 years of age with hypertension
Methods
- PRA measured using liquid chromatography-tandem mass spectrometry (LC/MS/MS)6,7:
- Angiotensin I generation and LC/MS/MS
- Quality control includes detection of peptidase degradation of angiotensin I for each sample (to improve accuracy)
- Analytical sensitivity: 0.04 ng/mL/h
- Analytical specificity: no known interferences
- PAC measured (if PRA ≤1.00 ng/mL/h) using LC/MS/MS
- Analytical sensitivity: 1.0 ng/dL
- Analytical specificity: no known interferences
- ARR (calculated if PAC ≥7.5 ng/dL) = PAC/PRA
Interpretive information
Interpretative information for the reflex pathway is depicted in the Figure.
For all screening results, consider the pretest probability (ie, prevalence) of PA in the patient’s population.
PRA >1.00 ng/mL/h is a negative screening result that suggests PA is unlikely:
- If a false negative is suspected based on medication use that raises PRA, consider retesting after withdrawing MRAs or epithelial sodium channel inhibitors (ENaCis) for 4 weeks or angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) for 2 weeks.3
PRA ≤1.00 ng/mL/h, PAC ≥7.5 ng/dL, and ARR >15.0 is a positive screening result that suggests overt PA is likely:
- Consider referral to a specialist.3
- If a false positive is suspected based on medication use that lowers PRA, consider retesting after withdrawing β-adrenergic blockers and centrally acting α2-agonists (eg, clonidine) for 2 weeks.3
PRA ≤1.00 ng/mL/h, PAC ≥7.5 ng/dL, and ARR ≤15.0 is a negative screening result that suggests PA is unlikely3:
- If a false negative is suspected based on a falsely low ARR, consider retesting after
- Withdrawing MRAs or ENaCis for 4 weeks or ACEis or ARBs for 2 weeks (withdrawal should lower PRA and raise ARR).3
- Ruling out or managing hypokalemia (Potassium, Plasma, test code 11014; normalizing potassium should raise PAC and raise ARR).3
PRA ≤1.00 ng/mL/h and PAC <7.5 ng/dL is a negative screening result that suggests PA is unlikely3 :
- Low PRA with low PAC results mostly indicates low-renin hypertension and may indicate rare clinical scenarios and genetic conditions.5
For pregnant women, older individuals, and patients with heart failure or renal failure, a clinician should consider changes in PRA and PAC associated with these conditions when interpreting screening results.3
References
- Hundemer GL, Vaidya A. Primary aldosteronism diagnosis and management: a clinical approach. Endocrinol Metab Clin North Am. 2019;48(4):681-700. doi:10.1016/j.ecl.2019.08.002
- Yang Y, Reincke M, Williams TA. Prevalence, diagnosis and outcomes of treatment for primary aldosteronism. Best Pr Res Clin Endocrinol Metab. 2020;34(2):101365. doi:10.1016/j.beem.2019.101365
- Adler GK, Stowasser M, Correa RR, et al. Primary aldosteronism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2025;110(9):2453-2495. doi:10.1210/clinem/dgaf284
- Marcelli M, Bi C, Funder JW, et al. Comparing ARR versus suppressed PRA as screening tests for primary aldosteronism. Hypertension. 2024;81(10):2072-2081. doi:10.1161/hypertensionaha.124.22884
- Monticone S, Losano I, Tetti M, et al. Diagnostic approach to low-renin hypertension. Clin Endocrinol. 2018;89(4):385-396. doi:10.1111/cen.13741
- Bystrom CE, Salameh W, Reitz R, et al. Plasma renin activity by LC-MS/MS: development of a prototypical clinical assay reveals a subpopulation of human plasma samples with substantial peptidase activity. Clin Chem. 2010;56(10):1561-1569. doi:10.1373/clinchem.2010.146449
- Haymond S, Clarke NJ, Reitz RE, et al. Plasma renin activity: the importance of correct sample type. Clin Chem. 2016;62(2):408-409. doi:10.1373/clinchem.2015.251009
Content reviewed 10/2025
This test is used to screen for primary aldosteronism.
Test Summary
Plasma Renin Activity With Reflex to Aldosterone
Test Code: 13817
Clinical use
- Screen for primary aldosteronism (PA)
Clinical background
PA is a treatable condition caused by one or both adrenal glands producing excess aldosterone, which can lead to hypertension, suppression of plasma renin, and low potassium levels. Patients with PA are at higher risk of cardiometabolic complications (eg, heart attack, heart failure, stroke, type 2 diabetes, atrial fibrillation).1 PA prevalence estimates range from 3% to 13% in the general population,2 up to 22% among patients with grade I through III hypertension, and up to 29% among those with resistant hypertension.3 Despite the high prevalence, screening rates for PA are extremely low and PA remains underdiagnosed, depriving patents of beneficial treatment, leading to suboptimal management, and exposing them to higher cardiovascular risk.3
The 2025 Endocrine Society guidelines on PA suggest that all patients with hypertension be screened for PA.3 Screening involves measuring both the plasma aldosterone concentration (PAC) and either direct renin concentration or plasma renin activity (PRA). In most circumstances, a positive screen is indicated by both (1) renin or PRA being low or suppressed and aldosterone levels being inappropriately high and (2) an elevated aldosterone-to-renin ratio (ARR).3 The guidelines also emphasize that screening results should be interpreted only after considering the methodology used for the test (eg, immunoassay or mass spectrometry), interfering medications (eg, mineralocorticoid receptor antagonists [MRAs]), and concurrent conditions (eg, hypokalemia, pregnancy, older age, heart or renal failure).3
Quest Diagnostics offers the Plasma Renin Activity Reflex to Aldosterone test (test code 13817), which is mass spectrometry-based testing that is consistent with guidelines for PA screening (measurement of direct renin concentration is not offered).3 Testing begins with measuring and reporting PRA; if PRA is ≤1.00 ng/mL/h, the patient’s PAC levels are measured and reported. According to the guidelines, the PRA and PAC results for these patients, combined with the calculated ARR, determine whether PA is likely (see Interpretive information and the Figure3–5 for details).3 PRA was chosen as the initial test based on a 2024 study that found that initial screening based on a PRA, rather than ARR, more efficiently identified patients with likely PA.4
The components of this reflex test can be ordered separately: Plasma Renin Activity (PRA), LC/MS/MS test (test code 16846), Aldosterone, LC/MS/MS test (test code 17181), and Aldosterone/Plasma Renin Activity Ratio, LC/MS/MS (test code 16845). Reflex testing is performed at an additional charge with an additional CPT code.
Individuals suitable for testing
- Individuals >16 years of age with hypertension
Methods
- PRA measured using liquid chromatography-tandem mass spectrometry (LC/MS/MS)6,7:
- Angiotensin I generation and LC/MS/MS
- Quality control includes detection of peptidase degradation of angiotensin I for each sample (to improve accuracy)
- Analytical sensitivity: 0.04 ng/mL/h
- Analytical specificity: no known interferences
- PAC measured (if PRA ≤1.00 ng/mL/h) using LC/MS/MS
- Analytical sensitivity: 1.0 ng/dL
- Analytical specificity: no known interferences
- ARR (calculated if PAC ≥7.5 ng/dL) = PAC/PRA
Interpretive information
Interpretative information for the reflex pathway is depicted in the Figure.
For all screening results, consider the pretest probability (ie, prevalence) of PA in the patient’s population.
PRA >1.00 ng/mL/h is a negative screening result that suggests PA is unlikely:
- If a false negative is suspected based on medication use that raises PRA, consider retesting after withdrawing MRAs or epithelial sodium channel inhibitors (ENaCis) for 4 weeks or angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) for 2 weeks.3
PRA ≤1.00 ng/mL/h, PAC ≥7.5 ng/dL, and ARR >15.0 is a positive screening result that suggests overt PA is likely:
- Consider referral to a specialist.3
- If a false positive is suspected based on medication use that lowers PRA, consider retesting after withdrawing β-adrenergic blockers and centrally acting α2-agonists (eg, clonidine) for 2 weeks.3
PRA ≤1.00 ng/mL/h, PAC ≥7.5 ng/dL, and ARR ≤15.0 is a negative screening result that suggests PA is unlikely3:
- If a false negative is suspected based on a falsely low ARR, consider retesting after
- Withdrawing MRAs or ENaCis for 4 weeks or ACEis or ARBs for 2 weeks (withdrawal should lower PRA and raise ARR).3
- Ruling out or managing hypokalemia (Potassium, Plasma, test code 11014; normalizing potassium should raise PAC and raise ARR).3
PRA ≤1.00 ng/mL/h and PAC <7.5 ng/dL is a negative screening result that suggests PA is unlikely3 :
- Low PRA with low PAC results mostly indicates low-renin hypertension and may indicate rare clinical scenarios and genetic conditions.5
For pregnant women, older individuals, and patients with heart failure or renal failure, a clinician should consider changes in PRA and PAC associated with these conditions when interpreting screening results.3
References
- Hundemer GL, Vaidya A. Primary aldosteronism diagnosis and management: a clinical approach. Endocrinol Metab Clin North Am. 2019;48(4):681-700. doi:10.1016/j.ecl.2019.08.002
- Yang Y, Reincke M, Williams TA. Prevalence, diagnosis and outcomes of treatment for primary aldosteronism. Best Pr Res Clin Endocrinol Metab. 2020;34(2):101365. doi:10.1016/j.beem.2019.101365
- Adler GK, Stowasser M, Correa RR, et al. Primary aldosteronism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2025;110(9):2453-2495. doi:10.1210/clinem/dgaf284
- Marcelli M, Bi C, Funder JW, et al. Comparing ARR versus suppressed PRA as screening tests for primary aldosteronism. Hypertension. 2024;81(10):2072-2081. doi:10.1161/hypertensionaha.124.22884
- Monticone S, Losano I, Tetti M, et al. Diagnostic approach to low-renin hypertension. Clin Endocrinol. 2018;89(4):385-396. doi:10.1111/cen.13741
- Bystrom CE, Salameh W, Reitz R, et al. Plasma renin activity by LC-MS/MS: development of a prototypical clinical assay reveals a subpopulation of human plasma samples with substantial peptidase activity. Clin Chem. 2010;56(10):1561-1569. doi:10.1373/clinchem.2010.146449
- Haymond S, Clarke NJ, Reitz RE, et al. Plasma renin activity: the importance of correct sample type. Clin Chem. 2016;62(2):408-409. doi:10.1373/clinchem.2015.251009
Content reviewed 10/2025