At what level of impaired renal function, as measured by estimated glomerular filtration rate (eGFR), would you stop Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin II Receptor Blockers (A2RB) in patients with advancing Chronic Kidney Disease (CKD)?

When to Stop ACEi/ARB in Advancing CKD

ACEi/ARB therapy should be continued even when eGFR falls below 30 ml/min/1.73 m² and should only be discontinued when eGFR falls below 15 ml/min/1.73 m² or in specific circumstances of intolerance. 1

Evidence-Based Recommendations for ACEi/ARB Management in CKD

When to Continue ACEi/ARB

• Continue ACEi/ARB therapy in patients with CKD even when eGFR falls below 30 ml/min/1.73 m² 1
• Benefits of continuing therapy include slowing CKD progression and cardiovascular protection 2
• Recent evidence suggests that discontinuation of ACEi/ARB therapy in patients with eGFR <30 ml/min/1.73 m² is associated with higher risk of mortality and major adverse cardiovascular events 3

When to Consider Dose Reduction or Discontinuation

1. eGFR <15 ml/min/1.73 m²: Consider reducing dose or discontinuing to reduce uremic symptoms while treating kidney failure 1
2. Symptomatic hypotension: Reduce dose or discontinue if patient experiences symptoms 1
3. Uncontrolled hyperkalemia: Discontinue only if hyperkalemia persists despite medical treatment 1
4. Acute kidney injury: Discontinue if serum creatinine rises by more than 30% within 4 weeks following initiation or dose increase 1

Monitoring Protocol for Patients on ACEi/ARB

Initial Monitoring

• Check serum creatinine, potassium, and blood pressure within 2-4 weeks of initiation or dose increase 1
• Continue therapy unless creatinine rises by >30% within 4 weeks 1

Ongoing Monitoring

• Regular monitoring of kidney function and potassium levels, especially in advanced CKD
• For patients with eGFR <30 ml/min/1.73 m², consider more frequent monitoring (every 1-3 months)

Management of Hyperkalemia

Hyperkalemia associated with ACEi/ARB use can often be managed without discontinuing therapy:

• Dietary potassium restriction
• Consider potassium binders rather than discontinuing RASi 1
• Adjust doses of other medications that may contribute to hyperkalemia
• Treat metabolic acidosis if present

Important Clinical Considerations

• Dosing: Use the highest approved dose that is tolerated to achieve maximum benefits 1
• Avoid combination therapy: Do not combine ACEi with ARB or direct renin inhibitors as this increases risk of hyperkalemia and acute kidney injury 1
• SGLT2 inhibitors: Consider adding SGLT2i for patients with eGFR ≥20 ml/min/1.73 m² for additional renoprotection 1

Common Pitfalls to Avoid

1. Premature discontinuation: Stopping ACEi/ARB therapy too early (before eGFR <15 ml/min/1.73 m²) may accelerate kidney disease progression and increase cardiovascular risk 3
2. Ignoring initial eGFR drop: A small initial decrease in eGFR (up to 30%) after starting ACEi/ARB is expected and not a reason to discontinue therapy 1
3. Inadequate monitoring: Failure to monitor kidney function and potassium levels after initiation or dose changes
4. Suboptimal dosing: Using subtherapeutic doses that don't provide maximum benefit 1
5. Failure to manage hyperkalemia: Not attempting dietary or pharmacological interventions before discontinuing therapy 1

The STOP-ACEi trial showed that discontinuing ACEi or ARB in advanced CKD did not slow the rate of eGFR decline, and discontinuation of ACEi appeared to have more unfavorable effects on kidney outcomes 4, further supporting the recommendation to continue these medications until very advanced stages of CKD.