How to manage resistant hypertension (HTN) in patients with end-stage renal disease (ESRD)?

Management of Resistant Hypertension in ESRD

For patients with resistant hypertension in end-stage renal disease (ESRD), the addition of low-dose spironolactone to existing treatment should be the first step in management, followed by other specific agents in a stepwise approach if spironolactone is not tolerated or effective. 1

Diagnostic Confirmation

Before initiating treatment, confirm true resistant hypertension by:

• Excluding pseudoresistance:
  • Verify BP measurements using out-of-office monitoring (24-hour ambulatory or home BP monitoring)
  • Assess medication adherence
  • Rule out white coat effect
• Evaluate volume status (most common cause in ESRD)
• Screen for secondary causes that may coexist with ESRD:
  • Renovascular disease
  • Primary aldosteronism
  • Sleep apnea

Treatment Algorithm

Step 1: Optimize Non-Pharmacological Approaches

• Strict sodium restriction (<2400 mg/day)
• Optimize dialysis prescription:
  • Evaluate and adjust dry weight
  • Consider increasing dialysis frequency or duration
  • Assess ultrafiltration rate

Step 2: Optimize Current Medication Regimen

• Ensure patient is on optimal doses of three different antihypertensive classes:
  • RAS blocker (ACE inhibitor or ARB)
  • Calcium channel blocker
  • Appropriate diuretic based on kidney function:
    • For ESRD patients: Loop diuretics if residual kidney function exists
    • Consider timing medications relative to dialysis sessions (some drugs are dialyzable)

Step 3: Add Fourth-Line Agent

• Add low-dose spironolactone (12.5-25 mg daily) if serum potassium <4.5 mmol/L 1
• Monitor potassium levels closely in ESRD patients

Step 4: If Spironolactone Is Not Tolerated or Ineffective

• Alternative options (in order of preference):
  1. Eplerenone (alternative MRA with fewer side effects)
  2. Beta-blocker (preferably bisoprolol or carvedilol)
  3. Alpha-blocker (doxazosin)
  4. Centrally acting agent (clonidine)
  5. Direct vasodilator (hydralazine or minoxidil) 1

Step 5: Consider Advanced Therapies

• For truly refractory cases, consider referral for:
  • Renal denervation (if performed at high-volume centers with expertise)
  • Evaluation for kidney transplantation (may resolve resistant hypertension) 2

Special Considerations in ESRD

• Volume control is paramount - most ESRD hypertension is volume-dependent 3, 4
• Medication timing relative to dialysis is critical:
  • Non-dialyzable medications may be preferred
  • For dialyzable medications, administer post-dialysis
• Intradialytic hypertension requires specific management:
  • Reassess dry weight
  • Consider non-dialyzable medications
• Monitor for orthostatic hypotension, especially with multiple agents

Common Pitfalls to Avoid

1. Failing to recognize volume overload as the primary driver of hypertension in ESRD
2. Not adjusting medication timing around dialysis sessions
3. Inadequate sodium restriction
4. Using inappropriate diuretics (thiazides are ineffective in ESRD)
5. Overlooking medication adherence issues
6. Not monitoring for hyperkalemia when using RAS blockers or MRAs

The management of resistant hypertension in ESRD requires a systematic approach with careful attention to volume status and medication selection. While spironolactone remains the preferred fourth-line agent according to the most recent guidelines 1, close monitoring of potassium levels is essential, and alternative agents should be used if contraindicated.