What is the treatment of resistant hypertension (HTN) in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD)?

Treatment of Resistant Hypertension in CKD and ESRD

The treatment of resistant hypertension in CKD and ESRD should focus on optimizing diuretic therapy with the addition of spironolactone, combined with complementary antihypertensive agents and strict sodium restriction. 1

Definition and Prevalence

Resistant hypertension in CKD is defined as:

• BP ≥130/80 mmHg despite using ≥3 antihypertensive medications with complementary mechanisms of action (one being a diuretic)
• OR requiring ≥4 medications to achieve BP control 1

Apparent treatment-resistant hypertension (aTRH) is extremely common in CKD patients:

• Affects approximately 40% of CKD patients 1
• CKD patients have 2-3 times higher risk of developing resistant hypertension 2
• More common in older patients, those with higher BMI, men, African Americans, and diabetics 1

Initial Evaluation

First, rule out pseudo-resistance:

• Confirm medication adherence
• Ensure proper BP measurement technique
• Exclude white coat hypertension using home or ambulatory BP monitoring
• Identify and discontinue interfering substances (NSAIDs, oral contraceptives) 1

Screen for secondary causes:

• CKD itself is a major cause of resistant hypertension due to impaired sodium excretion
• Obstructive sleep apnea
• Primary aldosteronism
• Renal artery stenosis 1

Treatment Algorithm

1. Lifestyle Modifications (Essential Foundation)

• Strict sodium restriction (crucial for CKD patients) 1
• Weight loss for overweight/obese patients
• DASH diet (modified for CKD if needed)
• Regular physical activity
• Limit alcohol consumption 1

2. Optimize Diuretic Therapy

• For CKD stages 1-3: Maximize thiazide or thiazide-like diuretics
  • Chlorthalidone is effective even in stage 4 CKD based on the CLICK trial 3
• For CKD stages 4-5 (non-dialysis): Consider loop diuretics (furosemide, torsemide)
• For ESRD on dialysis: Focus on volume control through ultrafiltration 4

3. Add Mineralocorticoid Receptor Antagonist

• Add spironolactone in low doses (12.5-25 mg daily) as the most effective fourth agent 1
• Monitor potassium levels closely, especially in advanced CKD
• Consider alternative agents if hyperkalemia develops 1

4. Ensure Complementary Medication Combinations

• Include a RAS blocker (ACEi or ARB) for patients with albuminuria 1
• Add a calcium channel blocker (preferably dihydropyridine)
• Consider beta-blockers if specific indications exist (CAD, heart failure)
• Avoid combination of ACEi, ARB, and direct renin inhibitors 1

5. Consider Additional Agents if Needed

• Alpha-blockers
• Central-acting agents (clonidine)
• Vasodilators (hydralazine, minoxidil) 1

Special Considerations for ESRD Patients on Dialysis

For hemodialysis patients:

• Focus on volume control through appropriate dry weight assessment and ultrafiltration
• Consider longer or more frequent dialysis sessions
• Schedule antihypertensive medications in relation to dialysis sessions (some may need to be held before dialysis) 4

For peritoneal dialysis patients:

• Optimize ultrafiltration through peritoneal dialysis prescription
• Consider icodextrin for long dwells to enhance volume removal 4

Common Pitfalls and How to Avoid Them

1. Overlooking medication non-adherence

   • Simplify regimens when possible
   • Use combination pills
   • Discuss barriers to adherence

2. Inadequate diuretic therapy

   • Ensure appropriate diuretic selection based on CKD stage
   • Consider combination of different classes of diuretics

3. Insufficient sodium restriction

   • Provide specific dietary counseling through a registered dietitian
   • Target <2 grams of sodium daily 1

4. Failure to recognize and address volume overload

   • Regular assessment of volume status
   • Adjust dry weight targets in dialysis patients

5. Hyperkalemia limiting use of RAS blockers and MRAs

   • Monitor potassium levels regularly
   • Consider potassium binders if appropriate
   • Use lower doses of these medications 1

Emerging Therapies

While current management relies primarily on pharmacological approaches, several emerging options show promise:

• SGLT2 inhibitors (for non-dialysis CKD)
• Endothelin receptor antagonists
• Aldosterone synthase inhibitors
• Non-steroidal mineralocorticoid receptor antagonists with lower hyperkalemia risk 3, 4

Interventional approaches like renal denervation have not shown consistent success but remain under investigation, particularly for patients with advanced CKD 1, 2.

By systematically addressing the multifactorial causes of resistant hypertension in CKD and ESRD patients with a focus on volume control, appropriate medication selection, and lifestyle modifications, blood pressure control can be improved, potentially reducing cardiovascular risk and slowing CKD progression.