What are the guidelines for using Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) in patients with End-Stage Renal Disease (ESRD) on Hemodialysis (HD)?

ACE Inhibitors and ARBs in ESRD on Hemodialysis

ACE inhibitors or ARBs can be used as second-line antihypertensive agents in ESRD patients on hemodialysis, but volume management through ultrafiltration and sodium restriction must be optimized first, with beta-blockers or calcium channel blockers preferred as first-line pharmacologic therapy. 1, 2

Primary Management Strategy

Volume control is the cornerstone of hypertension management in hemodialysis patients and must be addressed before adding medications. 1, 2

• Achieve dry weight through adequate ultrafiltration as the primary intervention 1, 2
• Enforce dietary sodium restriction consistently 1, 2
• Target predialysis blood pressure of 140/90 mmHg (measured sitting) 1, 2

First-Line Pharmacologic Therapy

When medications are needed after optimizing volume status:

Beta-blockers should be the preferred first-line agent, particularly for patients with previous myocardial infarction or established coronary artery disease, as they demonstrate the strongest mortality benefit in dialysis patients. 1, 2

Calcium channel blockers (such as amlodipine) are recommended as first-line therapy for hemodialysis patients without specific cardiovascular indications for beta-blockers. 1, 2

• Both beta-blockers and calcium channel blockers are associated with decreased mortality in observational studies of dialysis patients 2, 3

Role of ACE Inhibitors/ARBs as Second-Line Agents

ACE inhibitors or ARBs should be considered as second-line agents after beta-blockers or calcium channel blockers, particularly for patients with residual kidney function or left ventricular hypertrophy. 1, 2

Potential Benefits:

• Reduce left ventricular mass index in hemodialysis patients 1, 2, 3
• Preserve residual kidney function, which is particularly important in peritoneal dialysis patients 2
• May decrease mortality independent of blood pressure reduction in observational studies 2, 4
• Provide cardioprotective effects beyond blood pressure lowering 5

Critical Safety Concerns:

Use ACE inhibitors/ARBs with caution due to increased risk of hyperkalemia in dialysis patients. 1, 2

• Monitor serum potassium frequently when using these agents 1
• Hyperkalemia can be managed with dietary potassium restriction and potassium binders rather than discontinuing the medication 6

Never combine ACE inhibitors with ARBs, as this increases risks of hyperkalemia and acute kidney injury without additional benefit. 6, 7, 1, 2

Pharmacokinetic Considerations:

• Some ACE inhibitors (enalapril, ramipril, lisinopril) are removed by hemodialysis, while others (benazepril, fosinopril) are not 2, 3
• ARBs are not significantly removed by dialysis 2, 8, 9
• For dialyzable agents like lisinopril, thrice-weekly supervised administration after hemodialysis can enhance blood pressure control 3, 5
• Non-dialyzable agents may be preferred for patients prone to intradialytic hypotension 5

Specific Contraindications:

Avoid ACE inhibitors in patients using polyacrylonitrile (AN69) dialysis membranes due to risk of anaphylactoid reactions. 2, 3, 9

When ACE Inhibitors/ARBs Should Be Discontinued

Based on KDIGO 2021 guidelines for earlier CKD stages (which inform practice in ESRD):

• Consider reducing dose or discontinuing if serum creatinine rises >30% within 4 weeks of initiation 6
• Reduce dose or discontinue for symptomatic hypotension 6
• Reduce dose or discontinue for uncontrolled hyperkalemia despite medical management 6

Treatment Algorithm for ESRD on Hemodialysis

1. Optimize volume status first through ultrafiltration and sodium restriction 1, 2
2. If BP remains >140/90 mmHg, start beta-blocker (especially if coronary disease) or calcium channel blocker 1, 2
3. Add ACE inhibitor or ARB as second-line if BP still uncontrolled, monitoring potassium closely 1, 2
4. For resistant hypertension (BP >140/90 despite dry weight and three agents), evaluate for secondary causes and consider minoxidil 2

Common Pitfalls

• Starting antihypertensive medications before achieving dry weight leads to treatment failure 1, 2
• Using combination ACE inhibitor plus ARB therapy increases harm without benefit 6, 7, 1
• Failing to monitor potassium frequently when using ACE inhibitors/ARBs in dialysis patients 1
• Discontinuing ACE inhibitors/ARBs prematurely for mild hyperkalemia instead of managing potassium medically 6
• Ignoring the dialyzability of specific agents when timing doses 2, 3, 5