What is the recommended approach to using Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) in anuric hemodialysis patients with hypertension or heart failure?

ACE Inhibitors and ARBs in Anuric Hemodialysis Patients

ACE inhibitors and ARBs are not contraindicated in anuric hemodialysis patients and should be used when indicated for heart failure or hypertension, but require intensive monitoring for hyperkalemia, which develops in approximately 70% of patients, with 19% developing severe hyperkalemia necessitating drug withdrawal. 1, 2

Primary Indications for Use

ACE inhibitors and ARBs are specifically indicated in hemodialysis patients with:

• Heart failure with reduced ejection fraction (HFrEF) - These agents reduce morbidity and mortality in dialysis patients with dilated cardiomyopathy, with carvedilol showing comparable improvement to the general population in a randomized trial 1
• Atrial fibrillation - Clear evidence demonstrates reduced morbidity and mortality in dialysis patients with AF 3
• Hypertension - Should be considered first-line therapy when antihypertensive medication is needed, though formal superiority trials in dialysis populations are lacking 1, 3

Critical Safety Considerations

Hyperkalemia Risk (The Primary Concern)

In a prospective study of 112 anuric hemodialysis patients starting ACE inhibitor/ARB therapy: 2

• Mean serum potassium increased from 5.0 ± 0.4 mmol/L to 5.7 ± 0.5 mmol/L (p < 0.0001) 2
• Maximum potassium increased from 5.3 ± 0.5 mmol/L to 6.2 ± 0.6 mmol/L (p < 0.0001) 2
• Patients with normal potassium decreased from 82% to 29% 2
• Mild hyperkalemia (5.5-6.0 mmol/L) increased from 18% to 52% 2
• Severe hyperkalemia (>6.0 mmol/L) developed in 19% of patients, requiring drug withdrawal 2
• 31% required reduction in dialysate potassium concentration 2

After withdrawal of ACE inhibitor/ARB, potassium normalized within 1 month 2

Dialyzer Membrane Incompatibility

ACE inhibitors are absolutely contraindicated with polyacrylonitrile dialysis membranes due to risk of anaphylactoid reactions - Select ACE inhibitors that are not significantly dialyzed to maintain stable therapy 1

Monitoring Protocol

Implement the following intensive monitoring schedule:

• Baseline assessment: Serum potassium, creatinine, blood pressure 1, 4, 5
• Within 1-2 weeks of initiation: Repeat potassium and renal function 4, 5
• Pre-dialysis potassium monitoring: Check before each dialysis session during the first month, then at least weekly 2
• Watch for maximum potassium values after the long interdialytic interval (typically Monday or Tuesday sessions) 2
• Monitor blood pressure to avoid intradialytic hypotension 1

Management Algorithm for Hyperkalemia

When hyperkalemia develops on ACE inhibitor/ARB therapy:

1. Mild hyperkalemia (5.5-6.0 mmol/L): 2

   • Reduce dialysate potassium concentration (from 2.0 to 1.0 mmol/L)
   • Reinforce dietary potassium restriction
   • Continue ACE inhibitor/ARB with weekly potassium monitoring

2. Severe hyperkalemia (>6.0 mmol/L): 2

   • Immediately discontinue ACE inhibitor/ARB
   • Expect normalization within 1 month of withdrawal
   • Consider alternative antihypertensive agents (calcium channel blockers, beta-blockers)

Drug Selection Considerations

For heart failure in dialysis patients: 1

• Carvedilol is the preferred beta-blocker - Only agent with randomized trial data showing improved LV function, decreased hospitalization, and reduced cardiovascular and total mortality in dialysis patients with dilated cardiomyopathy 1
• ACE inhibitors should be used as adjunctive therapy, with dosing individualized around dialysis sessions to avoid intradialytic hypotension 1

Avoid dual RAS blockade: 4, 5

• Combination of ACE inhibitor + ARB increases risks of hyperkalemia and acute kidney injury without additional benefit 4, 5
• Do not combine with aliskiren 4, 5

Common Pitfalls to Avoid

• Do not assume anuric patients are protected from hyperkalemia - The 19% rate of severe hyperkalemia in anuric patients demonstrates significant risk 2
• Do not use standard dialysate potassium (2.0 mmol/L) universally - 31% of patients required reduction to 1.0 mmol/L 2
• Do not combine with potassium-sparing diuretics or potassium supplements - These are contraindicated 4, 5
• Do not use with polyacrylonitrile membranes - Risk of anaphylactoid reactions 1
• Do not withhold in patients with heart failure or AF - Benefits clearly outweigh risks when properly monitored 1, 3

Alternative Antihypertensive Strategies

If ACE inhibitor/ARB must be discontinued due to hyperkalemia: 1, 3

• Calcium channel blockers (amlodipine, nifedipine LA) are effective alternatives
• Beta-blockers provide cardiovascular protection, particularly in heart failure
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in HFrEF patients