What is the workup for resistant hypertension in Chronic Kidney Disease (CKD) stage 3?

From the Guidelines

The workup for resistant hypertension in CKD stage 3 should begin with confirming true resistance by ensuring proper blood pressure measurement technique and medication adherence, and then proceed with a comprehensive evaluation including laboratory testing, imaging studies, and assessment of volume status and contributing medications, as outlined in the most recent guidelines 1. The evaluation should include:

• Excluding pseudo-resistance by performing 24-hour ambulatory blood pressure monitoring or home BP monitoring
• Evaluating for secondary causes of hypertension, particularly those common in CKD patients, including renovascular disease, primary aldosteronism, obstructive sleep apnea, and pheochromocytoma
• Laboratory testing, such as:
  • Basic metabolic panel
  • Urinalysis
  • Urine albumin-to-creatinine ratio
  • Complete blood count
  • Thyroid function tests
  • Plasma aldosterone-to-renin ratio
  • 24-hour urine collection for sodium, potassium, metanephrines, and cortisol
• Imaging studies, such as:
  • Renal ultrasound with Doppler to assess for renal artery stenosis
  • CT or MR angiography if clinical suspicion is high The antihypertensive regimen should be optimized to include:
• A diuretic appropriate for the patient's GFR, such as a thiazide-like diuretic (e.g. chlorthalidone) for GFR >30 ml/min or a loop diuretic (e.g. furosemide) for lower GFR
• A renin-angiotensin system blocker (ACE inhibitor or ARB)
• A calcium channel blocker at maximally tolerated doses
• Consider adding a mineralocorticoid receptor antagonist like spironolactone (with careful potassium monitoring) or other agents such as beta-blockers or centrally acting agents if BP remains uncontrolled, as recommended in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1. Lifestyle modifications, including sodium restriction (<2g/day), weight loss, regular physical activity, and limiting alcohol intake, are essential components of management, and should be emphasized in conjunction with pharmacological therapy, as supported by the 2020 International Society of Hypertension global hypertension practice guidelines 1.

From the Research

Diagnosis and Evaluation

• Resistant hypertension is defined as blood pressure above targets despite treatment with at least three antihypertensive drugs in adequate dose and combination 2
• Accurate blood pressure measurement is essential for diagnosis and management of hypertension in patients with chronic kidney disease (CKD) 3
• 24-h ambulatory blood pressure monitoring can help identify 'white-coat', 'masked', and 'non-dipper' hypertension, which is particularly important in patients with resistant hypertension and CKD 4

Treatment Strategies

• For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen 3
• However, the use of spironolactone is restricted in patients with moderate-to-advanced CKD due to the risk of hyperkalemia 3
• Chlorthalidone, a thiazide-like diuretic, can be an effective alternative therapeutic option for patients with stage 4 CKD and uncontrolled hypertension, including those with treatment-resistant hypertension 3
• A triple combination of renin-angiotensin-aldosterone system antagonists, calcium channel blockers, and diuretics is a safe and effective therapy for resistant hypertension 2
• Fourth-line therapy may include the use of an aldosterone antagonist, such as spironolactone or amiloride 2, 5

Management of Resistant Hypertension in CKD Stage 3

• Patients with CKD stage 3 and resistant hypertension should be managed with a combination of lifestyle modifications, such as a low-salt diet, and antihypertensive medications 6
• The treatment regimen should include a diuretic, a renin-angiotensin-aldosterone system antagonist, and a calcium channel blocker, with the sequential addition of other antihypertensive drugs as needed 6
• Emerging agents, such as non-steroidal mineralocorticoid receptor antagonists, dual endothelin receptor antagonists, and aldosterone synthase inhibitors, may offer novel targets and strategies for controlling blood pressure in patients with resistant hypertension and CKD 3