Can Angiotensin-Converting Enzyme inhibitors (ACE-i) be started in patients with Chronic Kidney Disease (CKD)?

ACE Inhibitors in Chronic Kidney Disease

ACE inhibitors should be started in patients with CKD, particularly those with albuminuria, as they reduce both kidney disease progression and cardiovascular events. 1

Recommendations Based on Albuminuria and Diabetes Status

Non-Diabetic CKD:

• Strong recommendation (1B) to start ACE inhibitors or ARBs in patients with CKD and severely increased albuminuria (≥300 mg/24h or A3 category) even without hypertension 1, 2
• Weaker recommendation (2C) to start ACE inhibitors or ARBs in patients with CKD and moderately increased albuminuria (30-300 mg/24h or A2 category) 1
• Consider starting ACE inhibitors in patients with normal to mildly increased albuminuria (A1) for specific indications such as hypertension or heart failure 1

Diabetic CKD:

• Strong recommendation (1B) to start ACE inhibitors or ARBs in patients with diabetes, CKD, and moderately to severely increased albuminuria (A2 and A3 categories) 1
• Evidence from trials like IDNT and RENAAL shows clear reduction in kidney events compared to placebo or calcium-channel blockers 1

Monitoring and Safety Considerations

Initial Monitoring:

• Check serum creatinine and potassium within 2-4 weeks after initiation or dose increase 1, 3
• Continue ACE inhibitor therapy unless serum creatinine rises by more than 30% within 4 weeks of starting treatment 1
• A small initial decrease in GFR is expected and may actually predict long-term renoprotection 4

Ongoing Management:

• Use the highest approved dose that is tolerated to achieve maximum benefits 1
• Continue ACE inhibitors even when eGFR falls below 30 ml/min per 1.73 m² 1
• For patients with renal impairment, start with a lower dose (e.g., 1.25 mg ramipril daily) and titrate upward 3

Managing Adverse Effects:

• Hyperkalemia can often be managed with dietary measures, diuretics, or potassium-binding agents rather than stopping the ACE inhibitor 1, 3
• Consider reducing the dose or discontinuing ACE inhibitors in cases of:
  • Symptomatic hypotension 1, 3
  • Uncontrolled hyperkalemia despite medical treatment 1
  • Uremic symptoms in advanced kidney failure (eGFR <15 ml/min per 1.73 m²) 1

Special Considerations

Volume Status:

• Instruct patients to temporarily hold ACE inhibitors during periods of decreased oral intake, vomiting, or diarrhea to prevent acute kidney injury 2, 1
• In volume-depleted patients or those with renal artery stenosis, start with a lower dose (1.25 mg daily for ramipril) 3

Combination Therapy:

• Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor therapy as this increases adverse effects without additional benefit 1, 5
• Consider adding SGLT2 inhibitors in appropriate patients, which have complementary renoprotective effects 1
• For patients with residual proteinuria despite maximal ACE inhibitor therapy, consider adding a nonsteroidal mineralocorticoid receptor antagonist if eGFR >25 ml/min/1.73 m² and potassium is normal 1

Common Pitfalls:

• Discontinuing rather than never initiating ACE inhibitors is a common barrier to guideline-concordant care in proteinuric CKD 6
• Past acute kidney injury, hyperkalemia, advanced CKD, and lack of nephrology care are associated with lower use of ACE inhibitors, but these barriers may be inappropriate or modifiable 6
• Sodium depletion potentiates both beneficial and adverse effects of ACE inhibition; sodium restriction can improve therapeutic efficacy but requires careful monitoring 4

Efficacy Considerations

• ACE inhibitors and ARBs appear to have comparable efficacy in slowing kidney disease progression and reducing proteinuria 7
• The renoprotective effects are mediated through both blood pressure reduction and intrarenal mechanisms that reduce filtration pressure 4
• The benefits of ACE inhibitors in reducing cardiovascular events and kidney disease progression generally outweigh the risks of hyperkalemia and acute kidney injury for most patients 1