At what level of impaired renal function is lisinopril (angiotensin-converting enzyme inhibitor) contraindicated?

Lisinopril Dosing in Renal Impairment

Lisinopril requires dose adjustment when creatinine clearance (CrCl) falls below 30 mL/min, and should be used with caution in patients with severe renal impairment.

Renal Function Thresholds for Lisinopril

Lisinopril is primarily eliminated unchanged through the kidneys, making renal function a critical factor in its dosing. According to the evidence:

• Normal to moderate renal impairment (CrCl ≥30 mL/min): Standard dosing can be used with regular monitoring 1
• Severe renal impairment (CrCl <30 mL/min):
  • Dose adjustment required
  • Initial dose should be 2.5 mg daily 2
  • Maximum dose should not exceed 5 mg daily 1

Pharmacokinetic Considerations

The pharmacokinetics of lisinopril are significantly altered in renal impairment:

• Lisinopril is excreted unchanged in the urine 3
• Elimination half-life is relatively unchanged until CrCl falls below 30 mL/min 3
• With CrCl <30 mL/min:
  • Drug accumulation occurs 4
  • Peak and trough concentrations increase
  • Time to peak concentration is prolonged
  • Time to steady state is extended 3

Monitoring Recommendations

When using lisinopril in patients with impaired renal function:

• Measure baseline renal function before initiating therapy
• Monitor serum creatinine and potassium within 1 week of starting treatment or following dose escalation 1
• Temporarily suspend lisinopril during:
  • Intercurrent illness
  • Planned IV radiocontrast administration
  • Bowel preparation prior to colonoscopy
  • Major surgery 1

Special Considerations

• Hyperkalemia risk: Patients with renal impairment are at increased risk of developing hyperkalemia when taking lisinopril 5
• Renal function decline: A small initial increase in serum creatinine may occur after starting ACE inhibitors, which typically returns to baseline in most patients 1
• Contraindications:
  • Renal artery stenosis 1
  • Severe renal failure with rapidly changing renal function

Clinical Approach

1. Calculate CrCl using the Cockcroft-Gault formula
2. If CrCl ≥30 mL/min:
   • Start with standard dosing (typically 10 mg once daily)
   • Monitor renal function and electrolytes
3. If CrCl <30 mL/min:
   • Start with 2.5 mg once daily
   • Titrate cautiously if needed
   • Do not exceed 5 mg daily
   • Monitor renal function and electrolytes more frequently

Despite renal impairment concerns, ACE inhibitors like lisinopril have been shown to reduce microalbuminuria and progression toward end-stage renal dysfunction, making them valuable medications when used appropriately with proper monitoring 1.