When to start Angiotensin-Converting Enzyme (ACE) inhibitor or Angiotensin Receptor Blocker (ARB) in patients with diabetes?

When to Start ACE Inhibitors or ARBs in Diabetes

ACE inhibitors or ARBs should be initiated in all patients with diabetes who have albuminuria (urine albumin excretion ≥30 mg/24 hours), regardless of blood pressure status, with titration to the highest tolerated dose to reduce mortality and slow progression of kidney disease. 1

Indications for ACE Inhibitors or ARBs in Diabetes

Based on Albuminuria Status:

• Macroalbuminuria (>300 mg/24h):

  • Start ACE inhibitor or ARB even in normotensive patients (strong recommendation) 1
  • Titrate to the highest approved dose that is tolerated 1

• Microalbuminuria (30-300 mg/24h):

  • Start ACE inhibitor or ARB in patients with hypertension 1
  • Consider ACE inhibitor or ARB in normotensive patients 1

• No albuminuria (<30 mg/24h):

  • ACE inhibitor or ARB not specifically indicated for renoprotection
  • May be used for hypertension management based on other clinical factors 1

Based on Blood Pressure Status:

• With Hypertension (BP ≥130/80 mmHg):

  • Start ACE inhibitor or ARB immediately if albuminuria is present 1, 2
  • Target BP ≤130/80 mmHg for patients with albuminuria 1
  • Target BP ≤140/90 mmHg for patients without albuminuria 1

• Normotensive (BP <130/80 mmHg):

  • Start ACE inhibitor or ARB if macroalbuminuria is present 1
  • Consider ACE inhibitor or ARB if microalbuminuria is present 1

Monitoring After Initiation

1. Check serum creatinine and potassium within 2-4 weeks after starting or changing dose 1

2. Continue therapy unless:

   • Serum creatinine rises by more than 30% within 4 weeks
   • Uncontrolled hyperkalemia develops despite medical management
   • Symptomatic hypotension occurs 1

3. For hyperkalemia:

   • Consider managing with dietary potassium restriction
   • Review concurrent medications
   • Consider dose reduction before discontinuation 1

Important Considerations and Caveats

• Pregnancy: ACE inhibitors and ARBs are contraindicated during pregnancy due to risk of fetal harm 1, 2

• Dual RAS blockade: Avoid combining ACE inhibitors with ARBs as this increases risk of hyperkalemia and acute kidney injury without additional benefit 3

• Drug interactions: Monitor for interactions with NSAIDs, potassium supplements, and potassium-sparing diuretics 3

• Dose optimization: Titrate to the highest tolerated dose for maximum renoprotective effect 1

• Multiple agents: Most patients with diabetes and hypertension will require multiple agents to reach blood pressure targets 1

Evidence Quality and Controversies

• The recommendation for ACE inhibitors or ARBs in patients with macroalbuminuria is supported by strong evidence (1B) 1

• The recommendation for ACE inhibitors or ARBs in patients with microalbuminuria is supported by moderate evidence (2D) 1

• Recent meta-analysis suggests ARBs may be superior to ACE inhibitors in reducing risk of ESRD in patients with diabetes and albuminuria, though both reduce risk of doubling serum creatinine 4

• While ACE inhibitors have been more extensively studied in type 1 diabetes and ARBs in type 2 diabetes, their renoprotective effects are considered interchangeable 1

By following these evidence-based guidelines for initiating ACE inhibitors or ARBs in patients with diabetes, clinicians can significantly reduce the risk of kidney disease progression and improve long-term outcomes.