What are the management strategies for resistant hypertension in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Management of resistant hypertension in patients with Chronic Kidney Disease (CKD) should prioritize reinforcement of lifestyle measures, especially sodium restriction, and the addition of low-dose spironolactone to existing treatment, as recommended by the 2024 ESC guidelines 1.

Key Management Strategies

• Reinforcement of lifestyle measures, including sodium restriction, regular physical activity, weight management, limiting alcohol intake, and smoking cessation
• Addition of low-dose spironolactone to existing treatment, if the patient's potassium levels and kidney function allow
• Alternative fourth-line agents include beta-blockers, alpha-blockers, or centrally acting agents
• Medication adherence should be verified, and secondary causes of hypertension such as primary aldosteronism, renal artery stenosis, or obstructive sleep apnea should be investigated

Diuretic Therapy

• Diuretic therapy is essential to maximize blood pressure control in patients with resistant hypertension, with a preference for long-acting thiazide diuretics like chlorthalidone 1
• Loop diuretics may be necessary for effective volume and blood pressure control in patients with underlying CKD (creatinine clearance <30 mL/min)

Blood Pressure Monitoring

• Blood pressure monitoring should be performed regularly, with home measurements preferred to detect white coat or masked hypertension
• The target blood pressure for most CKD patients is <130/80 mmHg, though individualization based on comorbidities and tolerability is important

Additional Considerations

• Catheter-based renal denervation may be considered for resistant hypertension patients who have BP that is uncontrolled despite a three BP-lowering drug combination, and who express a preference to undergo renal denervation after a shared risk-benefit discussion and multidisciplinary assessment 1
• Referral to a specialist may be necessary for known or suspected secondary cause(s) of hypertension, or if BP remains uncontrolled after 6 months of treatment 1

From the FDA Drug Label

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)

The management strategies for resistant hypertension in patients with Chronic Kidney Disease (CKD) are not directly addressed in the provided drug label. However, it is mentioned that control of high blood pressure should be part of comprehensive cardiovascular risk management.

• The label suggests that many patients will require more than one drug to achieve blood pressure goals.
• It is recommended to refer to published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC), for specific advice on goals and management 2.

From the Research

Management Strategies for Resistant Hypertension in Patients with CKD

• Resistant hypertension in patients with Chronic Kidney Disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage, including cardiovascular disease and CKD progression 3.
• True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH), and management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications 3, 4.
• Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in managing resistant hypertension in patients with CKD 3.
• Medications typically include an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, a calcium channel blocker, and a long acting thiazide-type/like diuretic; if a fourth drug is needed, evidence supports addition of a mineralocorticoid receptor antagonist 5.
• Renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD, including aldosterone synthase inhibitors and dual endothelin receptor antagonists 6, 5, 3.
• A systematic approach to improve recognition and care for patients with resistant hypertension and CKD is recommended, including a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications 4.
• Patient education and engagement in the management process is important for sustained success, particularly in managing hyperkalemia, a common complication in patients with CKD using renin-angiotensin-aldosterone system inhibitors 7.

Treatment Options

• Non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive drug combinations, including diuretics 6.
• Renal denervation, a device-based approach that has been tested and approved for treatment-resistant hypertension 6, 5, 3.
• Novel agents, such as firibastat, aprocitentan, and baxdrostat, which have shown varied effectiveness in reducing blood pressure in patients with resistant hypertension 6.
• Mineralocorticoid receptor antagonists, which may provide benefit in patients with CKD and resistant hypertension 5, 4.

Considerations for Patients with CKD

• Patients with CKD have a two to three times higher risk of developing resistant hypertension 3.
• Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to treatment in CKD 3.
• The use of renin-angiotensin-aldosterone system inhibitors is critical in preventing cardiovascular disease and kidney function decline in patients with CKD, but can lead to hyperkalemia 7.
• Strategies to mitigate hyperkalemia, such as discontinuing non-RAAS inhibitor medications, correction of metabolic acidosis, and maximization of medication therapies that lower serum potassium, should be prioritized 7.