What is the management approach for a patient with hyperreninemia and normal aldosterone levels?

Management of High Renin with Normal Aldosterone

The most important first step is to evaluate for secondary causes of elevated renin, particularly renovascular hypertension from renal artery stenosis, which is the most common cause of this pattern and requires immediate assessment before considering other diagnoses. 1

Initial Diagnostic Approach

Assess for Secondary Hypertension

• Screen for renovascular disease using renal artery duplex ultrasound or CT angiography if you observe severe/refractory hypertension, flash pulmonary edema, or asymmetric kidney size on imaging 1
• Renal artery stenosis is the primary cause of combined elevated renin with elevated or normal aldosterone, representing physiologic activation of the renin-angiotensin-aldosterone system 1

Evaluate Medication Effects

• Discontinue interfering medications 2-4 weeks before repeat testing when clinically feasible, as diuretics, ACE inhibitors, ARBs, and beta-blockers all artificially elevate renin levels 1
• Beta-blockers cause highly significant renin suppression in essential hypertension, while ACE inhibitors and AT1 receptor antagonists decrease aldosterone only minimally 2
• If medications cannot be stopped, interpret results in the context of current therapy 3

Check Volume Status

• Assess for volume depletion, which physiologically elevates renin while aldosterone may remain normal if the stimulus is insufficient 1
• Ensure the patient had unrestricted salt intake before testing, as salt restriction elevates renin 3

Consider Atypical Primary Aldosteronism

When to Suspect This Diagnosis

High renin with normal aldosterone can represent an atypical presentation of primary aldosteronism in specific scenarios:

• Early-stage primary aldosteronism before hypertension develops or before volume expansion is sufficient to suppress renin 4
• Primary aldosteronism with secondary hypertensive kidney damage, where renal arteriolosclerosis allows renin to escape suppression despite autonomous aldosterone production 5
• Patients with severe, long-standing hypertension and elevated serum creatinine are at highest risk for this pattern 5

Diagnostic Clues

• Look for an elevated aldosterone-to-renin ratio despite elevated renin, as the aldosterone level may still be disproportionately high relative to renin 5
• The aldosterone-to-renin ratio remains useful for screening even when renin is not suppressed 5
• Check for hypokalemia, though it is absent in approximately 50% of primary aldosteronism cases 3

Confirmatory Testing Strategy

If Atypical Primary Aldosteronism is Suspected

The typical aldosterone-to-renin ratio screening is less reliable when renin is elevated, so proceed directly to confirmatory testing: 4

• Oral salt-loading test with 24-hour urine aldosterone measurement (failure to suppress aldosterone below threshold confirms autonomous production) 4
• Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis) 1
• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone secretion and causes false-negative results 1, 4

Treatment Algorithm

For Renovascular Hypertension

• Medical therapy is first-line for atherosclerotic renal artery stenosis, as the CORAL and ASTRAL trials demonstrated no benefit of stenting over medical management for blood pressure or renal function 1
• Consider revascularization only for refractory hypertension despite optimal medical therapy, progressive renal function decline, flash pulmonary edema, or fibromuscular dysplasia 1

For Confirmed Atypical Primary Aldosteronism

• Obtain non-contrast CT of adrenal glands to identify unilateral adenoma versus bilateral hyperplasia 4
• Adrenal venous sampling is mandatory before surgery, as CT findings alone lead to inappropriate surgery in 25% of cases 1, 4
• For unilateral disease: laparoscopic adrenalectomy provides complete biochemical cure in most patients 4
• For bilateral disease: long-term mineralocorticoid receptor antagonist therapy with spironolactone as first-line agent 4

Critical Pitfalls to Avoid

• Do not dismiss primary aldosteronism based on non-suppressed renin alone, as recent evidence shows it can occur in 11.3% of normotensive patients and in those with hypertensive kidney damage 4, 5
• Do not rely solely on aldosterone-to-renin ratio for diagnosis when renin is elevated—proceed directly to confirmatory suppression testing 4
• Monitor for severe hyperkalemia and creatinine elevation if starting spironolactone in patients with renal impairment, as they may have decreased filtered sodium load 5
• Patients with advanced hypertension and renal damage may still benefit from adrenalectomy or cautious spironolactone treatment, but require closer monitoring 5