What are the recommended blood and urine investigations for secondary hypertension?

Blood and Urine Investigations for Secondary Hypertension

All patients with suspected secondary hypertension should undergo basic screening with serum sodium, potassium, creatinine, eGFR, TSH, and dipstick urinalysis, followed by targeted advanced testing based on clinical clues. 1

Basic Screening Tests (Perform in All Suspected Cases)

Blood Tests

• Serum electrolytes: Sodium and potassium (hypokalemia suggests primary aldosteronism) 1
• Renal function: Serum creatinine and estimated glomerular filtration rate (eGFR) 1
• Thyroid function: TSH to exclude thyroid disorders 1
• Metabolic screening: Fasting glucose and lipid profile (if available) 1
• Liver function tests: To assess for metabolic causes 1
• Serum uric acid: Commonly elevated in hypertensive patients 1

Urine Tests

• Dipstick urinalysis: Initial screening for proteinuria and hematuria 1
• Urinary albumin-to-creatinine ratio (UACR): For quantification of proteinuria if dipstick is positive 1

Advanced Testing Based on Clinical Suspicion

For Primary Aldosteronism (8-20% of resistant hypertension)

When to suspect: Hypokalemia, muscle weakness/cramps, resistant hypertension, family history of early-onset hypertension 1, 2

• Aldosterone-to-renin ratio (ARR): First-line screening test; ratio >20 with elevated aldosterone and suppressed renin suggests primary aldosteronism 3, 2
• 24-hour urinary aldosterone: May be used as confirmatory testing 1

For Pheochromocytoma

When to suspect: Episodic sweating, palpitations, headaches, labile hypertension 1, 2

• Plasma free metanephrines: Most sensitive screening test 1
• 24-hour urinary catecholamines or metanephrines: Alternative screening method 1, 2

For Cushing Syndrome

When to suspect: Central obesity, facial plethora, striae, proximal muscle weakness 1

• Late-night salivary cortisol: Screening test for cortisol excess 1
• 24-hour urinary free cortisol: Alternative screening method 1
• Dexamethasone suppression test: Confirmatory testing 1

For Renovascular Disease

When to suspect: Abrupt onset or worsening hypertension, flash pulmonary edema, age >50 years with atherosclerotic disease 3, 2

• Basic renal function tests: Serum creatinine and eGFR (already included in basic screening) 1
• Note: Further evaluation requires imaging (renal artery duplex, CT/MR angiography), not additional blood/urine tests 1

For Renal Parenchymal Disease

When to suspect: History of UTIs, hematuria, family history of polycystic kidney disease 2

• Urinalysis with microscopy: To detect hematuria, proteinuria, casts 1
• UACR: Quantify degree of proteinuria 1
• Serum creatinine and eGFR: Assess degree of renal impairment (already in basic screening) 1

Algorithmic Approach to Testing

1. Start with basic screening in all patients: electrolytes, renal function, TSH, urinalysis 1, 3

2. Identify clinical clues from history, physical exam, and basic labs:

   • Hypokalemia → Check aldosterone-renin ratio 2
   • Episodic symptoms → Check plasma free metanephrines 1
   • Cushingoid features → Check late-night salivary cortisol 1
   • Proteinuria/hematuria → Check UACR and consider renal imaging 1

3. Proceed with targeted advanced testing only when clinical suspicion is high, as these tests are expensive and complex 4

4. Refer to specialist centers for confirmatory testing and management when screening tests are positive 1, 3

Critical Pitfalls to Avoid

• Do not perform expensive advanced testing before completing basic laboratory screening 2
• Medication interference: Beta-blockers and direct renin inhibitors lower renin levels, while mineralocorticoid receptor antagonists raise aldosterone, affecting ARR interpretation 2
• Exclude pseudoresistant hypertension and drug-induced hypertension before extensive workup 1
• Early detection is crucial: Delayed diagnosis leads to irreversible vascular remodeling, resulting in persistent hypertension even after treating the underlying cause 5