Can Angiotensin-Converting Enzyme inhibitors (ACEi) be started in patients with Chronic Kidney Disease (CKD) stage 3?

ACE Inhibitors in CKD Stage 3

Yes, ACE inhibitors can and should be started in patients with CKD stage 3, especially those with albuminuria, as they slow kidney disease progression and provide cardiovascular protection. 1

Indications for ACE Inhibitors in CKD Stage 3

• ACE inhibitors are recommended for patients with CKD stage 3 who have:

  • Severely increased albuminuria (A3) without diabetes (strong recommendation) 1
  • Moderately increased albuminuria (A2) without diabetes (suggested) 1
  • Moderately-to-severely increased albuminuria (A2 and A3) with diabetes (strong recommendation) 1
  • Hypertension (to achieve target BP <130/80 mmHg) 1
  • Heart failure with reduced ejection fraction 1

• Even in patients with normal to mildly increased albuminuria (A1), ACE inhibitors should be considered for specific indications such as hypertension or heart failure 1

Benefits of ACE Inhibitors in CKD Stage 3

• ACE inhibitors significantly decrease the risk of:

  • Kidney events (OR 0.54,95% CI 0.41-0.73) 2
  • Cardiovascular events (OR 0.73,95% CI 0.64-0.84) 2
  • Cardiovascular death (OR 0.73,95% CI 0.63-0.86) 2
  • All-cause death (OR 0.77,95% CI 0.66-0.91) 2

• ACE inhibitors are superior to ARBs and other antihypertensive drugs in preventing kidney events, cardiovascular outcomes, and mortality in non-dialysis CKD stages 3-5 2

Monitoring and Precautions

• Check changes in blood pressure, serum creatinine, and potassium within 2-4 weeks of initiation or dose increase 1

• Continue ACE inhibitor therapy unless:

  • Serum creatinine rises by more than 30% within 4 weeks of starting treatment 1
  • Patient develops symptomatic hypotension 1
  • Uncontrolled hyperkalemia occurs despite medical treatment 1

• Patients at risk for adverse effects include:

  • Those with volume depletion 3
  • Elderly patients with diabetes, coronary heart disease, or peripheral vascular disease (due to higher risk of renal artery stenosis) 4
  • Patients on concomitant potassium-sparing medications 5

Dosing Considerations

• Start with a low dose and titrate up ("start low - go slow"), especially in:

  • Patients at risk for renal artery stenosis 4
  • Patients pretreated with diuretics 4

• Aim for the highest approved dose that is tolerated, as proven benefits were achieved in trials using these doses 1

• Dose reduction is necessary in patients with renal insufficiency (with the exception of fosinopril) 4

Management of Adverse Effects

• Hyperkalemia:

  • Can often be managed by measures to reduce serum potassium rather than decreasing the dose or stopping ACE inhibitor 1
  • More common in advanced CKD but can be managed in most patients 6

• Acute decline in GFR:

  • A slight reduction in GFR at the onset of therapy is expected and may correlate with long-term renoprotection 3
  • This decline is usually reversible after withdrawal 3

Important Considerations

• Continue ACE inhibitor even when eGFR falls below 30 ml/min per 1.73 m² 1

• Avoid any combination of ACE inhibitor, ARB, and direct renin inhibitor in people with CKD (strong recommendation) 1, 6

• Sodium depletion potentiates both beneficial and adverse effects of ACE inhibitors 3:

  • Moderate reduction in dietary sodium intake can improve efficacy 5
  • Excessive sodium depletion can increase risk of adverse effects 3

By following these guidelines and monitoring protocols, ACE inhibitors can be safely and effectively started in patients with CKD stage 3, providing significant renoprotective and cardioprotective benefits.