What is the appropriate workup for a patient with uncontrolled hypertension and impaired renal function on dialysis, suspected of having primary hyperaldosteronism?

Workup for Primary Hyperaldosteronism in Dialysis Patients

In patients on dialysis with suspected primary hyperaldosteronism, proceed with aldosterone-to-renin ratio (ARR) screening despite the renal impairment, but interpret results cautiously as concurrent kidney disease can cause false-negative results due to renin escape from suppression. 1

Initial Screening Approach

Screen with ARR testing even in dialysis patients, as both resistant hypertension and impaired renal function are independent indications for primary aldosteronism screening. 1 The American College of Cardiology explicitly recommends ARR screening in patients with impaired renal function, recognizing that concurrent renal disease can interfere with test interpretation. 1

Patient Preparation Before Testing

• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 2, 1
• Discontinue interfering medications when clinically feasible: stop beta-blockers, centrally acting drugs, and diuretics, as these suppress renin and cause false-positive results. 2, 1
• Substitute with non-interfering antihypertensives: use long-acting calcium channel blockers or alpha-receptor antagonists, which minimally interfere with ARR. 2
• Withdraw mineralocorticoid receptor antagonists for at least 4 weeks before any testing. 2

Blood Collection Technique

• 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 collection. 2
• Ensure unrestricted salt intake before testing. 2

Interpreting ARR in Dialysis Patients

Critical Caveat for Renal Impairment

In patients with advanced kidney disease or dialysis, renin may "escape" from suppression despite true primary aldosteronism. 3, 4 This occurs because hypertensive kidney damage from aldosterone excess paradoxically increases renin levels, potentially causing false-negative ARR results. 3, 4

Positive Screening Criteria

• ARR ≥20-30 ng/dL per ng/mL/hr AND plasma aldosterone concentration ≥10-15 ng/dL. 2, 1
• Specificity improves if minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 2, 1

Special Interpretation in Dialysis

Even if renin is not fully suppressed (higher than expected), an elevated aldosterone/renin ratio with disproportionately high aldosterone levels can still indicate primary aldosteronism. 3 In three reported cases with severe hypertension and renal damage, patients had normal-to-high renin but still had elevated ARR due to inappropriately high aldosterone. 3

Confirmatory Testing

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion. 2, 1

Confirmatory Test Options

• Oral sodium loading test with 24-hour urine aldosterone measurement 2
• Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis) 2
• Fludrocortisone suppression test 2

Critical Consideration for Dialysis Patients

Standard confirmatory tests may be difficult to interpret or contraindicated in dialysis patients due to volume status concerns and inability to handle sodium loads. 1 If ARR is negative or borderline but clinical suspicion remains high, proceed to confirmatory testing. 1

Subtype Determination

Initial Imaging

• Obtain non-contrast CT scan of adrenal glands as initial imaging to identify unilateral adenoma versus bilateral hyperplasia. 2
• Choose imaging modalities that avoid iodinated contrast when possible for patients with chronic kidney disease. 1

Adrenal Venous Sampling (AVS)

AVS is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, as up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone. 2 AVS remains reliable even when renin is not suppressed due to concurrent renal disease. 1

Treatment Considerations for Dialysis Patients

Medical Management

Spironolactone should be avoided in patients with eGFR <30 mL/min or on dialysis due to dramatically increased hyperkalemia risk. 5, 3 However, three reported cases with advanced renal impairment responded to 200 mg spironolactone daily with increased serum creatinine and hyperkalemia, requiring careful monitoring. 3

Surgical Management

For unilateral disease, laparoscopic adrenalectomy remains the treatment of choice even in patients with renal impairment, as it can improve both blood pressure and potentially stabilize or improve renal function. 2, 6 One case report documented improvement in both BP and renal function after unilateral adrenalectomy in a patient with CKD. 6

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

Common Pitfalls in Dialysis Patients

• Do not assume normal or elevated renin excludes primary aldosteronism in patients with advanced kidney disease—look at the absolute aldosterone level and the ratio together. 3, 4
• Do not rely on hypokalemia as a screening trigger, as it is absent in approximately 50% of primary aldosteronism cases. 2
• Do not proceed to surgery based on CT findings alone—AVS is essential for lateralization. 2, 1
• Recognize that patients with higher baseline renin (renin "escape") have more severe renal damage and may have less favorable outcomes after treatment. 4