What is the initial workup for a patient with secondary hypertension from a nephrology perspective?

Secondary Hypertension Workup from a Nephrology Perspective

All patients with confirmed hypertension should be screened with a plasma aldosterone-to-renin ratio (ARR), as primary aldosteronism is the most common treatable renal cause of secondary hypertension, affecting 8-20% of resistant hypertension cases. 1, 2

When to Suspect Secondary Hypertension

Pursue aggressive workup in these clinical scenarios:

• Age of onset <30 years (or <40 years per ESC 2024 guidelines) 1, 3
• Resistant hypertension: BP >140/90 mmHg despite optimal doses of ≥3 antihypertensive drugs including a diuretic 1, 2
• Sudden onset or sudden deterioration of previously controlled hypertension 1, 3
• Hypertensive urgency or emergency 1, 3
• Target organ damage disproportionate to duration or severity of hypertension 1

Initial Laboratory Screening (Complete Before Imaging)

Basic panel for all suspected cases:

• Plasma aldosterone-to-renin ratio (ARR) - most critical test, now recommended for all confirmed hypertension 1, 2, 3
• Serum electrolytes (sodium, potassium) - hypokalemia strongly suggests primary aldosteronism 1, 3
• Serum creatinine and eGFR 1, 3
• Urinalysis with microscopy - look for blood, protein, and casts suggesting renal parenchymal disease 1, 3
• Urinary albumin-to-creatinine ratio 4, 1, 3
• Fasting blood glucose or HbA1c 1, 3
• Thyroid-stimulating hormone (TSH) 1, 3
• 12-lead ECG - assess for left ventricular hypertrophy 4, 3

Renal-Specific Clinical Clues

Renal Parenchymal Disease

Look for history of:

• Urinary tract infections, obstruction, hematuria 1
• Urinary frequency, nocturia 1
• Family history of polycystic kidney disease 1

Renovascular Disease (Renal Artery Stenosis)

Suspect when:

• Abrupt onset or worsening hypertension 1, 3
• Flash pulmonary edema 1, 3
• Serum creatinine increase ≥50% within one week of starting ACE inhibitor or ARB 3, 5
• Severe hypertension with unilateral smaller kidney or kidney size difference >1.5 cm 3, 5
• Abdominal systolic-diastolic bruit on examination 3

Targeted Renal Imaging

Only proceed after completing basic laboratory screening to avoid expensive unnecessary imaging 1, 3

For Renovascular Disease:

• Initial: Renal Duplex Doppler ultrasound 4, 2
• Confirmatory: CT or MRI renal angiography 4, 2, 3

For Renal Parenchymal Disease:

• Renal ultrasound to assess kidney size, echogenicity, and structural abnormalities 4

Confirmatory Testing for Primary Aldosteronism

When ARR is positive (ratio >20 with elevated aldosterone and suppressed renin):

• Confirmatory tests: Oral sodium loading test with 24-hour urine aldosterone OR IV saline infusion test with plasma aldosterone at 4 hours 3
• Localization studies: Adrenal CT scan, followed by adrenal vein sampling if surgical intervention is considered 3

Critical Pitfalls to Avoid

• Do not perform expensive imaging (CT, MRI, angiography) before completing basic laboratory screening 1, 3
• Medications affect ARR interpretation: Mineralocorticoid receptor antagonists raise aldosterone; beta-blockers and direct renin inhibitors lower renin 1
• Delayed diagnosis leads to vascular remodeling, affecting renal function and resulting in residual hypertension even after treating the underlying cause 1, 2
• Never combine two RAS blockers (ACE inhibitor + ARB) due to increased risk of hyperkalemia, hypotension, and acute kidney injury 3

Management Based on Renal Causes

Primary Aldosteronism:

• Unilateral disease: Laparoscopic adrenalectomy 1, 3
• Bilateral disease: Spironolactone 50-100 mg daily 1, 3

Renovascular Disease:

• Atherosclerotic renal artery stenosis: Medical therapy preferred (statin, antiplatelet, ACE inhibitor/ARB, cardiovascular risk optimization) 3
• Fibromuscular dysplasia: Percutaneous transluminal renal angioplasty without stenting 1, 3

Renal Parenchymal Disease:

• Address underlying renal disease with specific treatments 1
• Monitor renal function carefully when using RAS blockers 1

Resistant Hypertension Protocol (After Excluding Secondary Causes)

• Optimize diuretic therapy: Use thiazide-like diuretics (not classic thiazides); consider loop diuretics for eGFR <30 ml/min/1.73m² 1
• Add spironolactone as fourth-line agent if K+ <4.5 mmol/L and eGFR >45 ml/min/1.73m² 1, 3
• Consider renal denervation for resistant hypertension uncontrolled despite three-drug combination 1

Recognize that 5-10% of all hypertensive patients have secondary causes, increasing to 10-20% in resistant cases - maintain a high index of suspicion from a nephrology perspective. 3, 5