What are the considerations for using Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARB) in patients undergoing hemodialysis with hypertension or heart failure?

ACE Inhibitors and ARBs in Hemodialysis Patients

Direct Answer

ACE inhibitors and ARBs are not contraindicated in hemodialysis patients and can be used safely with appropriate monitoring, though they should be considered second-line agents after optimizing volume status and using beta-blockers or calcium channel blockers as first-line therapy. 1, 2

Primary Treatment Strategy

Volume management is the cornerstone of hypertension treatment in hemodialysis patients, not pharmacotherapy. 2, 3

• Achieve dry weight through adequate ultrafiltration as the first priority 2, 3
• Enforce dietary sodium restriction rigorously 2, 3
• Target predialysis blood pressure of 140/90 mmHg (sitting position) 2, 3

First-Line Pharmacologic Agents

When medications are needed after optimizing volume status:

Beta-blockers demonstrate the strongest mortality benefit and should be preferred for patients with previous myocardial infarction or established coronary artery disease. 2, 3

Calcium channel blockers (such as amlodipine) are recommended as first-line therapy for hemodialysis patients without specific cardiovascular indications for beta-blockers. 2, 3

• Observational data show calcium channel blockers reduce cardiovascular events compared to placebo in this population 2
• Beta-blockers showed fewer heart failure hospitalizations compared to ACE inhibitors in hemodialysis patients with left ventricular hypertrophy 2

Role of ACE Inhibitors/ARBs as Second-Line Agents

ACE inhibitors and ARBs should be used as second-line agents in hemodialysis patients, primarily for their effects on left ventricular mass reduction and residual kidney function preservation. 2, 3

Specific Benefits:

• Reduce left ventricular mass index in hemodialysis patients 2, 3
• Preserve residual kidney function, which is critically important for patients with significant remaining urine output 2, 3
• May reduce cardiovascular events based on limited trial data 4

Evidence Quality Considerations:

The evidence for ACE inhibitors/ARBs in hemodialysis is mixed and weaker than for other populations:

• One open-label trial showed ARBs reduced fatal/nonfatal cardiovascular events (HR 0.51) in hemodialysis patients, but the authors acknowledged the large effect may be spurious due to small sample size 4
• A large observational study found no mortality benefit from ACE inhibitors in maintenance hemodialysis patients 5
• Another observational study showed no benefit of ACE inhibitors or ARBs on mortality in dialysis patients, though benefits existed in earlier CKD stages 6
• The kidney-protective effects that make these drugs first-line in non-dialysis CKD patients are "less of a concern" in dialysis patients 1

Critical Safety Considerations

Absolute Contraindication:

Never administer ACE inhibitors to patients dialyzed with polyacrylonitrile (AN69) membranes due to risk of life-threatening anaphylactoid reactions. 1, 7, 8

Hyperkalemia Risk:

Monitor serum potassium within 1-2 weeks of initiation and regularly thereafter, as hyperkalemia is relatively common though typically modest (approximately 1 mEq/L increase). 1, 2, 7

• Avoid potassium supplements, potassium-containing salt substitutes, and potassium-sparing diuretics 7, 8, 9
• Risk is higher in patients with inadequate dialysis (Kt/V <2) or low peritoneal transport status 10
• In CAPD patients, standard doses of ACE inhibitors or ARBs have little effect on potassium despite aldosterone suppression, but caution is needed in inadequately dialyzed patients 10

Combination Therapy Warning:

Never combine ACE inhibitors with ARBs in hemodialysis patients—this increases risks of hyperkalemia and acute kidney injury without providing additional benefit. 2, 7, 9, 11

• Combined ACE inhibitor and ARB therapy was associated with increased cardiovascular death (HR 1.45) compared to ARB with non-ACEI antihypertensive 11
• The VA NEPHRON-D trial demonstrated increased adverse events without benefit from dual RAS blockade 9

Hypotension Risk:

ACE inhibitors and ARBs can cause symptomatic hypotension, particularly in volume-depleted patients or those with systolic blood pressure <100 mmHg. 8

• Consider withholding 24-48 hours before major surgery to reduce risk of profound intraoperative hypotension, though evidence is conflicting 1, 7

Medication Selection for Dialysis Patients

Select ACE inhibitors that are not significantly dialyzed to maintain stable therapy throughout the dialysis cycle. 1, 7

• Lisinopril is significantly dialyzed and may require timing adjustments 7
• Fosinopril and benazepril are not significantly removed by hemodialysis 3
• ARB levels do not change significantly during dialysis 3

Monitoring Requirements

Check serum potassium and creatinine within 1-2 weeks of initiation and regularly thereafter. 7

• Monitor blood pressure closely, especially in the first two weeks 8
• Assess for signs of hypotension, particularly around dialysis sessions 8

Common Pitfalls to Avoid

Do not discontinue ACE inhibitors or ARBs solely because a patient is on dialysis—they remain cardioprotective in appropriate patients. 7

Do not assume these drugs provide the same magnitude of benefit in dialysis patients as in earlier CKD stages—the evidence is substantially weaker. 1, 6, 5

Do not use ACE inhibitors or ARBs as first-line agents when beta-blockers or calcium channel blockers are more appropriate based on cardiovascular indications. 2, 3

Special Population: Patients with Residual Kidney Function

For hemodialysis patients with significant residual kidney function, ACE inhibitors or ARBs are particularly beneficial and should be strongly considered. 2, 3

• These agents slow the decline in residual kidney function, which is associated with better outcomes 2, 3
• Preservation of residual renal function is critically important for volume management and overall survival 2