What is the diagnosis and optimal management for a patient with resistant hypertension, elevated renin, hyperaldosteronism and sodium retention suggestive of secondary hyperaldosteronism?

Diagnosis and Management of Hyperaldosteronism with High Renin

This clinical presentation—hyperaldosteronism with elevated (not suppressed) renin, sodium retention, and resistant hypertension—indicates secondary hyperaldosteronism, most commonly from renovascular disease, and requires urgent imaging of the renal arteries with Doppler ultrasound or CT/MR angiography. 1

Understanding the Diagnostic Pattern

The combination of high aldosterone and high renin distinguishes secondary from primary hyperaldosteronism. In primary aldosteronism, renin is suppressed by aldosterone-mediated volume expansion, whereas in secondary hyperaldosteronism, renin remains elevated because it is the driver of aldosterone secretion. 2, 3

Key Diagnostic Features

• Elevated renin with hyperaldosteronism points to renovascular disease, renal parenchymal disease, or renin-secreting tumors as the underlying cause 4, 2
• Resistant hypertension (BP >140/90 mmHg on ≥3 drugs including a diuretic) is present in 5-34% of renovascular disease cases 1
• Sodium retention occurs because aldosterone drives renal sodium reabsorption, leading to volume expansion and hypertension 2

Immediate Diagnostic Work-Up

Essential Laboratory Tests

• Plasma aldosterone-to-renin ratio (ARR) should be measured, but in this case the absolute values matter more than the ratio—both hormones are elevated 1, 5
• Serum potassium may be low (hypokalemia supports hyperaldosteronism) or normal 1, 4
• Serum creatinine and eGFR to assess baseline renal function 1, 5
• Urinary albumin-to-creatinine ratio to detect renal damage 1, 5
• Basic metabolic panel including sodium (often elevated due to retention) 5

Critical Imaging Studies

Renal artery imaging is the cornerstone of diagnosis when renin is elevated:

• Renal Doppler ultrasound is the recommended first-line imaging modality 1, 5
• CT or MR renal angiography provides definitive diagnosis of renal artery stenosis 1
• Imaging should be performed urgently in patients with abrupt onset or worsening hypertension, flash pulmonary edema, or ≥50% creatinine rise after starting ACE inhibitors/ARBs 1, 5

Physical Examination Red Flags

• Abdominal systolic-diastolic bruit suggests renovascular disease 1, 5
• Flash pulmonary edema (jugular venous distension, peripheral edema) indicates severe bilateral renal artery stenosis 1, 5
• Radio-femoral pulse delay would suggest aortic coarctation 1, 6

Specific Etiologies to Consider

Renovascular Hypertension (Most Common)

Atherosclerotic renal artery stenosis accounts for most cases in older patients:

• Medical therapy with RAS blockade is the first-line treatment for atherosclerotic disease 1
• Stenting may be considered for bilateral stenosis, flash pulmonary edema, or refractory hypertension despite optimal medical therapy 1
• The CORAL trial showed no benefit of routine stenting for unilateral atherosclerotic stenosis 1

Fibromuscular dysplasia should be suspected in younger patients, especially women:

• Percutaneous transluminal renal angioplasty without stenting is the treatment of choice 1, 5
• This is a systemic vascular disease that may affect carotid and other arteries 1

Accessory Renal Arteries

• Variant vascular anatomy can cause renovascular hypertension leading to secondary hyperaldosteronism 4
• Detected by CT or MR angiography 4
• May require surgical intervention or renal denervation in resistant cases 4

Renal Artery Stenosis Post-Surgical Complications

• Patients with prior abdominal aortic aneurysm repair can develop renal artery stent stenosis 7
• Presents with hypokalemia, metabolic alkalosis, and uncontrolled hypertension months to years after surgery 7

Hypertensive Kidney Damage in Primary Aldosteronism

Important caveat: Patients with longstanding primary aldosteronism can develop hypertensive nephrosclerosis that causes renin to "escape" from suppression, creating a mixed picture with elevated aldosterone and elevated renin. 3

• These patients still have an elevated aldosterone-to-renin ratio because aldosterone is disproportionately high 3
• Serum creatinine is typically elevated 3
• They respond to spironolactone but may develop marked hyperkalemia and creatinine elevation 3
• This represents advanced disease with vascular remodeling 3

Treatment Algorithm

Step 1: Optimize Medical Therapy While Completing Work-Up

• ACE inhibitors or ARBs are the drugs of choice for high-renin hypertension 2
• Aliskiren (direct renin inhibitor) is an alternative 2
• Monitor renal function carefully—a ≥50% creatinine rise within one week suggests bilateral stenosis or stenosis of a solitary kidney 1, 5
• Avoid combining two RAS blockers (ACE inhibitor + ARB) due to increased risk of hyperkalemia and acute kidney injury 5

Step 2: Address the Underlying Cause

For atherosclerotic renal artery stenosis:

• Medical therapy is recommended as first-line treatment (Class I, Level A) 1
• Optimize cardiovascular risk management with statins and antiplatelet therapy 1
• Consider revascularization (stenting) only for refractory hypertension, worsening renal function, or flash pulmonary edema 1

For fibromuscular dysplasia:

• Angioplasty without stenting is the treatment of choice 1, 5
• This can restore renal perfusion and lower blood pressure 1

For bilateral severe stenosis (>75%):

• Individualized decision-making is required 1
• Trial of RAS blockade with careful monitoring, or proceed to intervention if creatinine rises >30% or flash pulmonary edema develops 1

Step 3: Adjunctive Therapy

• Aldosterone antagonists (spironolactone 50-100 mg daily or eplerenone) can be added to control hyperaldosteronism 1, 4, 2
• Use cautiously if eGFR <45 mL/min/1.73m² or potassium >4.5 mmol/L 5
• In patients with hypertensive kidney damage and primary aldosteronism, spironolactone may cause marked hyperkalemia 3

Step 4: Resistant Hypertension Protocol

If blood pressure remains uncontrolled:

• Ensure adherence to a three-drug regimen (RAS blocker, calcium channel blocker, thiazide-like diuretic) at maximal doses 5
• Add spironolactone as fourth-line agent if potassium and renal function permit 5
• Consider alternative fourth-line agents (doxazosin, bisoprolol) 5
• Renal denervation may be considered for truly resistant cases 6

Common Pitfalls to Avoid

• Failing to image the renal arteries when renin is elevated—this is the critical diagnostic step 1
• Assuming primary aldosteronism based on hyperaldosteronism alone without checking renin 4, 2
• Starting RAS blockade without monitoring creatinine in patients with suspected bilateral stenosis 1, 5
• Delaying diagnosis—vascular remodeling from chronic renovascular hypertension can cause irreversible renal damage and residual hypertension even after revascularization 1, 6
• Overlooking medication-induced hypertension (NSAIDs, decongestants, oral contraceptives) before extensive work-up 1, 5
• Performing expensive imaging before basic laboratory screening is complete 6, 5

When to Refer

• Positive screening tests requiring confirmatory procedures (e.g., renal angiography with possible intervention) 1, 6, 5
• Complex cases where the diagnosis remains unclear despite initial work-up 1, 6
• Consideration of revascularization for renal artery stenosis 1
• Persistent uncontrolled blood pressure after 6 months of optimal medical therapy 6