Ordering PAC, PRA, and ARR Simultaneously
Yes, you should order PAC and PRA (or direct renin concentration) at the same time from a single blood draw—the ARR is simply calculated from these two values, not ordered as a separate test. 1
How the Screening Works
The aldosterone-to-renin ratio (ARR) is not a separate laboratory test that you order independently. Rather, it is a calculated value derived from simultaneously measuring:
- Plasma aldosterone concentration (PAC)
- Plasma renin (either as plasma renin activity [PRA] or direct renin concentration [DRC])
Both measurements must come from the same blood draw under standardized conditions 1, 2.
Proper Screening Protocol
Sample Collection Requirements
Order both PAC and renin together with these conditions 1, 2:
- Morning collection after patient has been awake >2 hours
- Seated position for 5-15 minutes before draw
- Normal potassium levels (≥4 mmol/L)—hypokalemia suppresses aldosterone and causes false negatives
- Unrestricted salt intake (minimum 5 g/day NaCl) for several days prior
- Slow venous draw to avoid hemolysis and spurious potassium elevation
Interpreting the Results
A positive screen requires both conditions 1:
- Suppressed renin (the hallmark finding)
- Elevated ARR:
- ARR >20 (aldosterone in ng/dL, PRA in ng/mL/h) by immunoassay
- ARR >70 (aldosterone in pmol/L, DRC in mU/L) by immunoassay
- ~25% lower thresholds when using LC-MS/MS for aldosterone measurement
Critical Pitfalls
The ARR Alone Is Insufficient
Do not rely solely on an elevated ARR. With very low renin levels, the ARR can be falsely elevated even when aldosterone is inappropriately low 2. This is why you need the absolute aldosterone value alongside the ratio—aldosterone should typically be >10 ng/dL (277 pmol/L) when PA is suspected 1, 2.
High Intra-Individual Variability
Research demonstrates substantial variability in ARR measurements 3:
- Sample coefficient of variation: 41-42% for ARR
- 38% of confirmed PA patients had at least one ARR below the diagnostic threshold
- This supports obtaining at least 2 ARR measurements before excluding PA
Medication Interference
While screening can be performed on usual antihypertensive therapy 2, be aware:
- Avoid screening while on: MRAs, diuretics (withdraw 4 weeks if safe)
- May cause false positives: β-blockers, α-2 agonists (lower renin)
- May cause false negatives: ACE inhibitors, ARBs (raise renin)
- If initial screen is positive on β-blockers and aldosterone is 10-15 ng/dL by immunoassay, consider repeating off medication 1
Why This Matters for Patient Outcomes
Proper screening identifies patients who benefit from:
- Surgical cure in unilateral disease (greatest cardiovascular risk reduction)
- Targeted MRA therapy in bilateral disease (significant but lesser cardiovascular benefit)
- Prevention of PA-related complications: stroke, MI, atrial fibrillation, heart failure 2
The key is that both values must be obtained simultaneously from properly collected samples to calculate a meaningful ARR—you cannot order them separately or calculate the ratio retrospectively from different time points.