At what GFR should ACE (Angiotensin-Converting Enzyme) inhibitors or ARBs (Angiotensin Receptor Blockers) not be initiated?

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Last updated: September 7, 2025View editorial policy

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ACE Inhibitors and ARBs Should Not Be Initiated When GFR is Below 30 mL/min/1.73 m²

ACE inhibitors and ARBs should not be initiated in patients with a GFR below 30 mL/min/1.73 m², though they may be continued with careful monitoring if already established on therapy and providing benefit 1, 2.

GFR Thresholds for ACE/ARB Initiation

The decision to initiate ACE inhibitors or ARBs should be guided by the following GFR thresholds:

  • GFR ≥ 30 mL/min/1.73 m²: May initiate ACE inhibitors or ARBs with appropriate monitoring
  • GFR < 30 mL/min/1.73 m²: Do not initiate ACE inhibitors or ARBs 1, 2

The KDIGO guidelines specifically recommend against using immunosuppressive therapy in patients with serum creatinine ≥ 3.5 mg/dL (or eGFR ≤ 30 mL/min/1.73 m²) 1. This principle extends to ACE inhibitors and ARBs due to their potential to cause further deterioration in renal function in advanced kidney disease.

Monitoring Recommendations When Using ACE/ARBs

When initiating ACE inhibitors or ARBs in patients with GFR ≥ 30 mL/min/1.73 m²:

  • Check serum creatinine and potassium within 1 week of starting or increasing the dose 3
  • Expect a potential increase in serum creatinine of up to 30% from baseline, which is generally acceptable 4
  • Discontinue if serum creatinine rises more than 30% above baseline during the first 2 months of therapy 4
  • Monitor for hyperkalemia, especially in patients with reduced GFR 2

Special Considerations

Continuing vs. Initiating Therapy

  • Continuation: ACE inhibitors or ARBs may be continued in patients whose GFR declines below 30 mL/min/1.73 m² while on therapy, as long as they are tolerating the medication without significant adverse effects 5
  • Initiation: New starts should be avoided when GFR is already below 30 mL/min/1.73 m² 1, 2

Temporary Discontinuation ("Sick Day Rules")

Temporarily discontinue ACE inhibitors and ARBs in patients with GFR < 60 mL/min/1.73 m² during:

  • Serious intercurrent illness
  • Planned IV radiocontrast administration
  • Bowel preparation for colonoscopy
  • Major surgery
  • Situations with high risk of acute kidney injury 1, 3

Contraindications

Absolute contraindications to ACE inhibitors or ARBs include:

  • Bilateral renal artery stenosis
  • Previous angioedema with ACE inhibitors
  • Pregnancy
  • Hyperkalemia (serum potassium > 5.5 mmol/L) 2

Common Pitfalls to Avoid

  1. Failure to monitor renal function: Always check creatinine and potassium after initiation
  2. Premature discontinuation: Don't stop therapy for minor increases in creatinine (<30%)
  3. Combination therapy: Never use ACE inhibitors and ARBs simultaneously 1
  4. Ignoring hyperkalemia risk: Monitor potassium levels closely, especially in patients with reduced GFR
  5. Failure to temporarily discontinue during acute illness: Follow "sick day rules" to prevent acute kidney injury

Conclusion

While ACE inhibitors and ARBs provide significant cardiovascular and renoprotective benefits in many patients, the threshold for initiation should be a GFR of at least 30 mL/min/1.73 m². Below this threshold, the risks of hyperkalemia, acute kidney injury, and further deterioration of renal function generally outweigh the potential benefits when starting these medications.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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