Why are Angiotensin-Converting Enzyme (ACE) inhibitors discontinued when starting dialysis?

ACE Inhibitors and Dialysis: Considerations for Discontinuation

ACE inhibitors are not contraindicated in patients with end-stage renal disease and are frequently used in dialysis patients, but they should not be administered to patients treated with polyacrylonitrile dialysis membranes due to the risk of anaphylactoid dialyzer reactions. 1

Primary Reasons for ACE Inhibitor Discontinuation When Starting Dialysis

• Hyperkalemia risk: ACE inhibitors can cause significant hyperkalemia in end-stage renal disease patients, with studies showing an increase in serum potassium from 4.9 ± 0.2 to 5.5 ± 0.2 mM in dialysis patients on ACE inhibitors 2

• Anaphylactoid reactions: ACE inhibitors should not be administered to patients treated with polyacrylonitrile dialysis membranes due to the risk of potentially life-threatening anaphylactoid reactions 1

• Hemodynamic instability: Patients on dialysis are prone to hypotension during ultrafiltration, and ACE inhibitors may exacerbate this effect by preventing compensatory vasoconstriction through angiotensin II blockade 1

Hyperkalemia Management Considerations

• Hyperkalemia is relatively common in ACE inhibitor-treated patients with uremia, with increases in plasma potassium generally around 1 mEq/L 1

• Patients with end-stage renal disease on dialysis have approximately five times higher risk of developing hyperkalemia with ACE inhibitors compared to those with normal renal function 3

• Hyperkalemia frequently complicates ACE inhibitor-associated acute renal failure, requiring careful monitoring and potentially discontinuation 1

When ACE Inhibitors Can Be Continued in Dialysis

• If the patient is not using polyacrylonitrile dialysis membranes 1

• When hyperkalemia can be adequately managed through dialysis 2

• When selecting an ACE inhibitor that is not significantly dialyzed to maintain stable therapy 1

Benefits of Continuing ACE Inhibitors When Possible

• Discontinuation of RAAS inhibitors after hyperkalemia is associated with higher mortality (HR 1.32-1.47) and cardiovascular mortality (HR 1.28-1.32) compared to continuation 4

• RAAS inhibitor discontinuation after hyperkalemia is associated with a higher risk of kidney or all-cause mortality composite outcome (adjusted HR 1.21) mainly driven by all-cause mortality (adjusted HR 1.34) 5

• ACE inhibitors provide cardiovascular protection in patients with heart failure, which remains important even in dialysis patients 3

Monitoring Recommendations

• Monitor serum potassium levels regularly, especially in the early period after initiating dialysis 1

• Assess for signs of hypotension during dialysis sessions, particularly in the first few treatments after starting dialysis 1

• Consider the type of dialysis membrane being used, with absolute contraindication for polyacrylonitrile membranes 1

Clinical Decision Algorithm

1. Assess dialysis membrane type:

   • If polyacrylonitrile membrane: Discontinue ACE inhibitor due to anaphylactoid reaction risk 1
   • If other membrane type: Proceed to next step

2. Evaluate potassium management:

   • If pre-dialysis K+ consistently >5.5 mEq/L: Consider discontinuation 1
   • If K+ can be maintained <5.5 mEq/L with dialysis: Consider continuing 2

3. Assess hemodynamic stability:

   • If significant intradialytic hypotension: Consider discontinuation 1
   • If hemodynamically stable: Consider continuing

4. Consider cardiovascular benefit:

   • If high cardiovascular risk/heart failure: Stronger case for continuing if other factors permit 3, 4
   • If low cardiovascular risk: Less compelling need to continue

Common Pitfalls to Avoid

• Automatic discontinuation: Not all patients starting dialysis require ACE inhibitor discontinuation; decisions should be based on specific contraindications 1

• Ignoring membrane type: Failure to recognize the specific contraindication with polyacrylonitrile membranes 1

• Overlooking cardiovascular benefits: Discontinuing ACE inhibitors without considering their mortality benefits in high-risk cardiovascular patients 5, 4

• Inadequate potassium monitoring: Failing to monitor serum potassium levels frequently enough in dialysis patients on ACE inhibitors 1