What are the best Angiotensin-Converting Enzyme Inhibitors (ACEi) and Angiotensin Receptor Blockers (ARB) for patients with end-stage Chronic Kidney Disease (CKD)?

Best ACEi and ARB for End-Stage CKD

For patients with end-stage chronic kidney disease (CKD), losartan is the preferred ARB due to its proven efficacy in diabetic nephropathy and established safety profile in advanced kidney disease. 1

Recommendations for RAS Inhibitors in End-Stage CKD

General Principles

• RAS inhibitors (ACEi or ARB) should be continued in patients with CKD even when eGFR falls below 30 ml/min/1.73 m², as they provide cardiovascular and renal protection 2
• Consider reducing the dose or discontinuing ACEi or ARB in end-stage CKD (eGFR <15 ml/min/1.73 m²) only if experiencing:
  • Symptomatic hypotension
  • Uncontrolled hyperkalemia despite medical treatment
  • Need to reduce uremic symptoms 2

Specific Agent Selection

ARBs

• Losartan is specifically indicated for diabetic nephropathy with elevated serum creatinine and proteinuria, making it the preferred ARB for end-stage CKD 1
• Losartan reduces the rate of progression of nephropathy as measured by doubling of serum creatinine or progression to end-stage renal disease 1
• Losartan has demonstrated efficacy in preventing progression to ESRD in patients with type 2 diabetes and overt nephropathy 3

ACEi

• ACEi therapy has shown superior outcomes compared to other antihypertensive drugs in non-dialysis CKD stages 3-5, with the highest benefits for prevention of kidney events, cardiovascular outcomes, and all-cause mortality 4
• However, ACEi use in end-stage CKD carries a higher risk of hyperkalemia compared to ARBs 5, 4

Monitoring and Safety Considerations

Hyperkalemia Management

• Monitor serum potassium closely when using RAS inhibitors in end-stage CKD 2
• Hyperkalemia associated with RAS inhibitors can often be managed by measures to reduce serum potassium levels rather than decreasing the dose or stopping therapy 2
• Consider potassium binders if hyperkalemia develops 2

Renal Function Monitoring

• Check changes in blood pressure, serum creatinine, and serum potassium within 2-4 weeks of initiation or dose increase 2
• Continue ACEi or ARB unless serum creatinine rises by more than 30% within 4 weeks following initiation or dose increase 2

Contraindications and Precautions

• Avoid any combination of ACEi, ARB, and direct renin inhibitor therapy as this increases risk of hyperkalemia and acute kidney injury without additional benefits 2, 1
• NSAIDs should be used with extreme caution in patients on RAS inhibitors with end-stage CKD due to risk of further deterioration of renal function 1

Dosing Considerations

• RAS inhibitors should be administered using the highest approved dose that is tolerated to achieve maximum benefits 2
• Dose adjustments may be needed based on individual patient response and laboratory parameters 2
• For patients with severe hyperkalemia risk, consider lower starting doses with careful titration 5

Special Situations

• In patients with heart failure and end-stage CKD, ACEi/ARB therapy provides additional cardiovascular benefits 2
• For patients with type 2 diabetes and CKD, consider adding an SGLT2 inhibitor if eGFR ≥20 ml/min/1.73 m² 2
• If a patient cannot tolerate ACEi due to cough (more common with ACEi than ARBs), switching to an ARB is recommended 4

By following these evidence-based recommendations, clinicians can optimize the use of RAS inhibitors in patients with end-stage CKD while minimizing adverse effects and improving outcomes related to morbidity, mortality, and quality of life.