What is the best approach for screening a patient with suspected primary aldosteronism, particularly with impaired renal function and potential renal artery stenosis?

Screening for Primary Aldosteronism in Patients with Impaired Renal Function and Potential Renal Artery Stenosis

Screen with the plasma aldosterone-to-renin ratio (ARR) even in the presence of renal impairment or suspected renal artery stenosis, but recognize that concurrent RAS can cause false-negative results by preventing renin suppression, requiring additional confirmatory testing and potentially adrenal venous sampling despite a negative ARR. 1, 2, 3

Who Should Be Screened

Screen this patient immediately given the clinical presentation of resistant hypertension with impaired renal function and potential RAS, as both conditions independently warrant PA screening. 1

Specific indications for PA screening include:

• Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) 1
• Hypokalemia (spontaneous or substantial if diuretic-induced) 1
• Incidentally discovered adrenal mass 1
• Family history of early-onset hypertension or stroke at young age (<40 years) 1

Critical Challenge: Concurrent RAS Complicates PA Diagnosis

The presence of renal artery stenosis creates a diagnostic trap because RAS elevates renin levels, which can mask the low renin typically seen in PA, resulting in a falsely normal or negative ARR. 2, 3

• PA with concurrent RAS patients have significantly lower mean ARR values (38.4 vs. 87.4 ng/dL per ng/mL/h) compared to PA patients without RAS 3
• The false-negative rate for ARR screening reaches 50% in PA patients with concurrent RAS, compared to only 15% in PA patients without RAS 3
• Even severe hydronephrosis causing renal ischemia can elevate renin sufficiently to produce negative ARR results in confirmed PA cases 4

Patient Preparation Before Testing

Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 1, 5

Medication management:

• Discontinue beta-blockers, centrally acting drugs, and diuretics when clinically feasible, as these suppress renin and cause false-positive results 5
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing 5
• Use long-acting calcium channel blockers and alpha-receptor antagonists as alternatives during the screening period, as they minimally interfere with ARR 5
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking 1

However, in patients with impaired renal function and potential RAS, medication adjustments must be balanced against clinical safety, and testing may need to proceed on current medications with appropriate interpretation. 1

Blood Collection Protocol

Collect blood in the morning (ideally 0800-1000 hours) with the patient out of bed for 2 hours prior and seated for 5-15 minutes immediately before blood draw. 5

• Blood should be drawn with the patient in a seated position 1
• Ensure unrestricted salt intake before testing 5

Interpreting the ARR in This Clinical Context

A positive screening test requires BOTH:

• ARR ≥20-30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) 1, 5
• Plasma aldosterone concentration ≥10-15 ng/dL 1, 5
• Specificity improves if minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1, 5

Critical caveat for this patient: If the ARR is negative or borderline but clinical suspicion remains high (resistant hypertension, hypokalemia, impaired renal function), do NOT stop the evaluation. 4, 2, 3

Proceed to Confirmatory Testing Despite Negative ARR

When RAS is present or suspected, proceed directly to confirmatory testing even if the ARR is negative, because the elevated renin from RAS can mask PA. 4, 2, 3

Confirmatory test options:

• Intravenous saline suppression test: Infuse 2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms autonomous aldosterone secretion 1, 5
• Oral sodium loading test with 24-hour urine aldosterone measurement 1, 5
• Fludrocortisone suppression test 5

Testing requirements:

• Perform with unrestricted salt intake and normal serum potassium levels 1, 5
• Mineralocorticoid receptor antagonists should be withdrawn at least 4 weeks before testing 5

Imaging Considerations in Renal Impairment

For patients with chronic kidney disease, choose imaging modalities that avoid iodinated contrast when possible. 1

• Imaging for renal artery stenosis should be reserved for patients with increased suspicion (young patients suggesting fibromuscular dysplasia, older patients at risk for atherosclerotic disease) 1
• For patients with CKD, modalities that do not involve iodinated contrast may be preferred over CT angiography 1
• Diagnostic renal arteriograms in the absence of suspicious noninvasive imaging are not recommended 1

Adrenal Venous Sampling: Essential in Complex Cases

If confirmatory testing suggests PA despite a negative or borderline ARR, proceed to adrenal venous sampling to establish lateralization, as this remains reliable even when renin is not suppressed due to concurrent RAS. 2, 3

• Adrenal venous sampling can successfully identify unilateral aldosterone over-secretion even when RAS prevents renin suppression 2
• This is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease 5

Referral Pathway

Refer all patients with positive screening tests or high clinical suspicion despite negative ARR to a hypertension specialist or endocrinologist for confirmatory testing, subtype determination, and treatment planning. 1, 5

Management of Concurrent Conditions

If both PA and RAS are confirmed, consider two-stage treatment:

• First, address the renal artery stenosis with percutaneous transluminal renal angioplasty if indicated 2
• Then, reevaluate for persistent PA after successful revascularization, as residual hypertension or hypokalemia after RAS treatment strongly suggests coexisting PA 2, 3
• If PA persists, proceed to laparoscopic adrenalectomy for unilateral disease or mineralocorticoid receptor antagonist therapy for bilateral disease 2

Common Pitfalls to Avoid

• Do not rely on the presence or absence of hypokalemia alone, as it is absent in approximately 50% of PA cases 5
• Do not stop the diagnostic evaluation after a single negative ARR in patients with high clinical suspicion, especially with concurrent RAS 4, 2, 3
• Do not proceed to surgery based on CT findings alone without adrenal venous sampling, as up to 25% of patients might undergo unnecessary adrenalectomy 5
• Monitor for hyperkalemia risk in patients with renal impairment when using mineralocorticoid receptor antagonists, particularly with concurrent use of ACE inhibitors, ARBs, or NSAIDs 6