When should Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARBs) be stopped in patients with impaired renal function?

When to Stop ACE Inhibitors/ARBs in Patients with Renal Failure

ACE inhibitors or ARBs should be temporarily discontinued when serum creatinine increases by more than 30% from baseline within the first 2 months of therapy, when potassium levels exceed 5.6 mmol/L, or in conditions of acute renal hypoperfusion such as volume depletion, hypotension, or concurrent use of nephrotoxic medications. 1, 2

Monitoring Parameters and Thresholds for Discontinuation

Serum Creatinine Thresholds

• A 10-20% increase in serum creatinine after starting ACE inhibitors/ARBs is expected and acceptable 1, 3
• Discontinue if:
  • Serum creatinine rises >30% from baseline within first 2 months of therapy 3
  • For patients with baseline creatinine >2.0 mg/dL, discontinue if increase exceeds 1.0 mg/dL 1
  • Oliguria or anuria develops 1

Potassium Monitoring

• Discontinue if serum potassium exceeds 5.6 mmol/L despite management 2
• Risk of hyperkalemia is 5 times higher in patients with chronic renal insufficiency (creatinine >1.5 mg/dL) 3

Clinical Scenarios Requiring Discontinuation

Acute Kidney Injury Risk Conditions

1. Volume depletion:

   • Dehydration from diuretics, diarrhea, vomiting
   • Severe hyperglycemia with osmotic diuresis 1

2. Hemodynamic compromise:

   • Systemic hypotension (MAP <65 mmHg) 2
   • Worsening heart failure with reduced cardiac output 1
   • Sepsis 1

3. Concurrent medications:

   • NSAIDs administration
   • Cyclosporine therapy
   • Radiocontrast procedures (temporarily hold before and after) 1, 2

4. Renal vascular disease:

   • Bilateral renal artery stenosis
   • Unilateral stenosis in a solitary kidney 1, 4

Restarting After Discontinuation

After temporary discontinuation for AKI, ACE inhibitors/ARBs can be restarted when:

1. Renal function has returned to baseline or stabilized 2
2. Volume status is optimized (euvolemic) 2
3. Precipitating factors have been corrected 2
4. Blood pressure is adequate (MAP >65 mmHg) 2

Dosing Strategy When Restarting

• For creatinine clearance >30 mL/min: standard dosing
• For creatinine clearance 10-30 mL/min: reduce initial dose by 50%
• For creatinine clearance <10 mL/min: start at 25% of normal dose 2

Special Considerations

Diabetic Nephropathy

Despite potential risks, ACE inhibitors/ARBs provide significant benefits in diabetic nephropathy:

• Delay progression of nephropathy in type 1 diabetes with any degree of albuminuria 1
• Delay progression to macroalbuminuria in type 2 diabetes with microalbuminuria 1
• Delay progression of nephropathy in type 2 diabetes with macroalbuminuria and renal insufficiency 1

End-Stage Renal Disease

• ACE inhibitors are not contraindicated in patients with end-stage renal disease 1
• Avoid in patients treated with polyacrylonitrile dialysis membranes (risk of anaphylactoid reactions) 1
• Select ACE inhibitors that are not significantly dialyzed for patients on hemodialysis 1

Perioperative Management

• Consider holding ACE inhibitors/ARBs 24-48 hours before major surgery to reduce risk of intraoperative hypotension 1

Common Pitfalls to Avoid

1. Inappropriate discontinuation: A small (10-20%) rise in creatinine is expected and not a reason to discontinue therapy 1, 3

2. Substituting ARBs during AKI recovery: ARBs exert similar effects on renal hemodynamics and should not be substituted when ACE inhibitors cause renal dysfunction 1, 4

3. Overlooking the long-term benefits: Despite initial creatinine rise, ACE inhibitors/ARBs provide long-term renoprotection in chronic kidney disease 3, 5

4. Ignoring drug selection based on elimination pathway: For patients with variable renal function, consider ACE inhibitors with partial hepatic clearance (e.g., fosinopril, spirapril) rather than those eliminated solely by renal excretion 1, 6, 7

By carefully monitoring renal function and following these guidelines, the benefits of ACE inhibitors/ARBs can be maximized while minimizing the risk of adverse renal outcomes in patients with impaired kidney function.