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July 04, 2025

Plasma Renin Activity & Aldosterone: Essential Testing for Hypertension Treatment

Plasma renin activity and aldosterone levels are critical in evaluating hypertension. This test helps determine whether high blood pressure is fluid-driven or vasoconstrictive in nature—and what treatment is best.

Plasma Renin Activity & Aldosterone: Essential Testing for Hypertension Treatment

Plasma Renin Activity & Aldosterone: The Cornerstone of Personalized Hypertension Treatment

Hypertension affects nearly half of U.S. adults and remains one of the most underdiagnosed and mismanaged conditions in modern medicine. For too long, high blood pressure has been treated with a one-size-fits-all approach. But not all hypertension is created equal—and the key to unlocking truly effective, long-term management lies in understanding each patient's unique physiologic drivers. That’s where plasma renin activity (PRA) and aldosterone testing come into play.

These two simple blood tests can distinguish between different types of hypertension—most notably high renin versus low renin hypertension—and guide more precise, effective, and safer treatment strategies. Unfortunately, these tests are often skipped or ordered after medication has already begun, which alters results and obscures the real picture.

In this post, we’ll explore how PRA and aldosterone testing works, what the results mean, and how they dramatically impact the way we treat high blood pressure.

Why Plasma Renin and Aldosterone Testing Matters

Most clinicians are taught to treat hypertension in stages using generic algorithms. While this works for some patients, many continue to struggle with uncontrolled or medication-resistant hypertension. That’s because hypertension can stem from entirely different mechanisms in different people.

Before initiating most blood pressure medications (with the exception of certain calcium channel blockers like amlodipine), patients should undergo plasma renin activity and aldosterone testing to determine the underlying pathophysiology of their elevated blood pressure.

Skipping this step can result in:

  • Ineffective treatment choices

  • Unnecessary side effects

  • Missed diagnoses of secondary hypertension

  • Long-term harm to organs due to persistent dysfunction

What Is Plasma Renin Activity?

Plasma renin activity (PRA) measures the activity of the renin-angiotensin-aldosterone system (RAAS). Renin is an enzyme secreted by the kidneys in response to low blood flow, sodium depletion, or sympathetic nervous system activation. It catalyzes the conversion of angiotensinogen to angiotensin I, a precursor to angiotensin II—a powerful vasoconstrictor that also stimulates aldosterone release.

PRA provides insight into whether a person’s hypertension is driven more by:

  • Vasoconstriction and sympathetic activation (high renin)

  • Volume overload and sodium retention (low renin)

What Is Aldosterone?

Aldosterone is a hormone produced by the adrenal glands that promotes sodium retention and potassium excretion by the kidneys. It’s a key player in regulating extracellular fluid volume and blood pressure.

When renin is high, aldosterone is typically high as well—this is the body’s attempt to conserve fluid in the face of perceived low blood volume or perfusion. But sometimes aldosterone becomes elevated independently of renin, which can signal conditions like primary hyperaldosteronism (Conn’s syndrome).

Understanding the balance—or imbalance—between these two hormones is critical for choosing the correct treatment.

Interpreting the Results: High vs. Low Renin Hypertension

The threshold used to distinguish renin status is typically a PRA of 0.65 ng/mL/hr:

  • PRA > 0.65 ng/mL/hr = High Renin Hypertension

  • PRA < 0.65 ng/mL/hr = Low Renin Hypertension

According to published literature, about 70% of hypertensive patients have high renin hypertension, while the remaining 30% have low renin physiology.

Physiologic Differences: Two Very Different Types of Hypertension

Understanding which side of the 0.65 line a patient falls on can completely reshape how we interpret their hypertension and treat it effectively.

High Renin Hypertension

  • Mechanism: Driven primarily by excessive activation of the renin-angiotensin-aldosterone system (RAAS).

  • Triggers: Renal hypoperfusion, sympathetic overactivity, stress, dehydration, and high catecholamine states.

  • Features:

    • Increased vasoconstriction

    • Narrowed blood vessels

    • Often younger patients or those with kidney issues

  • Lab Pattern:

    • PRA > 0.65

    • Aldosterone normal or elevated

  • Treatment:

    • ACE inhibitors (e.g., lisinopril)

    • ARBs (e.g., losartan)

    • Beta blockers (preferably carvedilol or nebivolol)

    • Direct renin inhibitors (e.g., aliskiren—less commonly used)

Low Renin Hypertension

  • Mechanism: More related to sodium retention and plasma volume expansion than vasoconstriction.

  • Triggers: Primary aldosteronism, high sodium intake, insulin resistance, chronic kidney disease.

  • Features:

    • Expanded plasma volume

    • Suppressed renin output

    • Often older adults, African Americans, or those with metabolic syndrome

  • Lab Pattern:

    • PRA < 0.65

    • Aldosterone may be high, normal, or low

  • Treatment:

    • Mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone)

    • Thiazide-like diuretics (though not HCTZ—see our HCTZ warning)

    • Sodium restriction

    • Magnesium and potassium repletion

Why You Must Test Before Medications

The most important clinical takeaway is this: PRA and aldosterone levels should be tested before starting antihypertensive medications, especially those that interfere with RAAS.

Most antihypertensives (except dihydropyridine calcium channel blockers like amlodipine) significantly affect the RAAS and render renin and aldosterone levels unreliable. This includes:

  • ACE inhibitors

  • ARBs

  • Beta blockers

  • Diuretics

  • Spironolactone

  • Eplerenone

Once a patient starts on these medications, their PRA and aldosterone levels may be altered for weeks—even if the drug is discontinued. That’s why we always urge early testing before initiating long-term therapy.

Clinical Examples

Case 1: High Renin Hypertension

John, age 48, presents with systolic BP of 145 mmHg. No medications yet. He has chronic stress, poor sleep, and a high resting heart rate. Labs show:

  • PRA = 2.1 ng/mL/hr

  • Aldosterone = 11 ng/dL

Interpretation: High renin hypertension likely driven by sympathetic overactivity.

Treatment Plan:

  • Begin ACE inhibitor (lisinopril 10mg)

  • Add magnesium glycinate

  • Begin mindfulness-based stress reduction

  • Consider beta blocker (nebivolol) if HR remains elevated

Case 2: Low Renin Hypertension

Maria, age 62, has systolic BP of 150 mmHg despite lifestyle interventions. She eats a salty processed diet and struggles with central obesity. Labs show:

  • PRA = 0.2 ng/mL/hr

  • Aldosterone = 14 ng/dL

Interpretation: Low renin hypertension, likely from sodium overload and possible subclinical hyperaldosteronism.

Treatment Plan:

  • Initiate low-sodium DASH diet

  • Start eplerenone 25mg

  • Supplement potassium and magnesium

  • Monitor for improvement and consider adrenal imaging if aldosterone stays elevated

Integrating PRA and Aldosterone Testing into Functional Medicine

At Revolution Health, we incorporate PRA and aldosterone testing as part of every comprehensive hypertension evaluation. It’s especially useful when combined with:

With this data, we can develop personalized treatment plans that may include:

  • Targeted medication choices

  • Peptide therapies such as BPC-157 or TB-500 for vascular support

  • Key supplements like Magnesium Glycinate, Vascanox, Arterosil, and CoQ10 (targeting >2 mcg/mL)

  • Lifestyle strategies including DASH, Mediterranean diet, and zone 2 cardio

  • Toxin testing when environmental exposures may be a factor

Final Thoughts: Precision, Not Guesswork

Understanding your renin and aldosterone levels is like having a roadmap to your blood pressure dysfunction. Without it, providers are flying blind, trying medication after medication with little understanding of why something works—or doesn’t.

With it, we can:

  • Choose the right medications from the start

  • Avoid drug interactions

  • Reduce side effects

  • Possibly eliminate medications long-term

  • Identify serious secondary causes early

And best of all, you’ll feel empowered knowing your care plan is based on your physiology, not a pharmaceutical guessing game.

Ready to Get Tested?

If you’ve never had your plasma renin activity and aldosterone levels tested—or if you’re on blood pressure medications but still not feeling your best—it’s time for a deeper dive. At Revolution Health, we offer in-depth testing and personalized care plans to help you optimize your cardiovascular health.

Call today or schedule online to start your evaluation.
Ask about renin-aldosterone testing before making any medication changes.

References

  1. Laragh JH, Sealey JE. "The Plasma Renin Test Revealed: Guidelines for Interpretation and Use in Hypertension." Am J Hypertens. 2011.

  2. Funder JW, Carey RM, et al. "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment." J Clin Endocrinol Metab. 2016.

  3. Kaplan NM. "Low-Renin Hypertension." Hypertension. 2004.

  4. Calhoun DA, et al. "Resistant Hypertension: Diagnosis, Evaluation, and Treatment." Circulation. 2008.

  5. Williams B, et al. "Practice Guidelines for Hypertension." JAMA. 2018.