What does plasma renin activity (PRA) measure?

What Does Plasma Renin Activity Measure?

Plasma renin activity (PRA) measures the enzymatic activity of renin in converting angiotensinogen to angiotensin I, serving as a functional assessment of the renin-angiotensin-aldosterone system's activity. 1

Physiologic Basis

PRA reflects the functional capacity of the renin-angiotensin system rather than simply the amount of renin protein present. 2 The test measures how much angiotensin I is generated per unit time when plasma renin acts on its substrate angiotensinogen, typically reported in ng/mL/hour. 1

Clinical Applications

Primary Use: Screening for Primary Aldosteronism

PRA is primarily used as the denominator in calculating the aldosterone-to-renin ratio (ARR), which screens for primary aldosteronism. 1 In primary aldosteronism, autonomous aldosterone production suppresses renin secretion, resulting in:

• Elevated plasma aldosterone concentration (≥10-15 ng/dL) 3
• Suppressed PRA (typically <0.5 ng/mL/h) 3
• Elevated ARR (>30 when aldosterone is in ng/dL and PRA in ng/mL/h) 1

Evaluation of Renovascular Hypertension

PRA helps assess the renin-angiotensin system's response to renal hypoperfusion. 1 In renovascular disease:

• Renal artery stenosis causes elevated PRA due to decreased renal perfusion pressure 1
• The captopril test measures PRA before and 60 minutes after 50 mg oral captopril, with sensitivity of 61% and specificity of 86% for detecting renal artery disease 1
• However, PRA is not recommended as a screening test for renal artery stenosis due to false-negative rates of 43% and false-positive rates of 34% 1

Renal Vein Renin Measurements

PRA can be measured from renal veins to lateralize renin production. 1 A renal vein renin ratio >1.4:1 with hypertension duration <5 years predicts 95% cure rate after revascularization. 1 However, renal vein renin measurements have been largely supplanted by noninvasive imaging and are now performed infrequently. 1

Technical Considerations

Test Methodology

The enzyme kinetic PRA test using radioimmunoassay has the required sensitivity to detect low renin states, whereas direct renin assays and PRA tests with short incubation times are usually not accurate enough. 2 Plasma prorenin must not cryoactivate to renin during sample handling to avoid falsely elevated values. 2

Medication Effects

All medications affecting the renin-angiotensin-aldosterone system must be stopped for at least 2 weeks before testing to maximize accuracy: 1

• Beta-blockers increase PRA and can cause false-positive ARR 4
• ACE inhibitors and ARBs increase PRA and decrease ARR 4
• Diuretics increase PRA 1
• Calcium channel blockers and alpha-1 blockers minimally affect ARR and can be continued if stopping all antihypertensives is unsafe 1, 3

Patient Preparation

• Maintain dietary sodium intake of 100-200 mmol/day 1
• Ensure potassium repletion, as hypokalemia suppresses aldosterone production 3
• Collect blood after 2 hours upright and 5-15 minutes seated 3

Interpretation Pitfalls

Approximately 15% of patients with essential hypertension have elevated PRA, which can cause false-positive results when screening for renovascular disease. 1 Conversely, volume expansion, chronic renal failure, bilateral renal artery disease, or disease in a solitary kidney can suppress PRA and cause false-negative results. 1

For primary aldosteronism screening, the specificity of ARR improves when a minimum PRA threshold of 0.5 ng/mL/h is used in calculations, as extremely low renin can artificially elevate the ratio even without truly elevated aldosterone. 3