What is the recommended starting dose and titration schedule of lisinopril in adults with impaired renal function based on creatinine clearance?

Lisinopril Renal Dosing

For patients with impaired renal function, lisinopril requires dose reduction based on creatinine clearance: no adjustment needed if CrCl >30 mL/min; reduce initial dose to 50% (2.5-5 mg daily) if CrCl 10-30 mL/min; and start at 2.5 mg daily for hemodialysis patients or CrCl <10 mL/min, with maximum titration to 40 mg daily as tolerated. 1

Dosing by Creatinine Clearance

Normal to Mild Renal Impairment (CrCl >30 mL/min)

• No dose adjustment required 1
• Standard starting doses apply:
  • Hypertension: 10 mg once daily (or 5 mg if on diuretics) 1
  • Heart failure: 5 mg once daily (or 2.5 mg if hyponatremic with sodium <130 mEq/L) 1
  • Post-MI: 5 mg initially, then 5 mg at 24 hours, 10 mg at 48 hours, then 10 mg daily 1

Moderate Renal Impairment (CrCl 10-30 mL/min)

• Reduce initial dose to 50% of standard dose 1
  • Hypertension: Start at 5 mg once daily 1
  • Heart failure: Start at 2.5 mg once daily 1
  • Post-MI: Start at 2.5 mg once daily 1
• Titrate upward as tolerated to maximum 40 mg daily 1
• Accumulation is highly correlated with creatinine clearance in this range 2
• Effective half-life doubles compared to normal renal function 2

Severe Renal Impairment (CrCl <10 mL/min or Hemodialysis)

• Start at 2.5 mg once daily regardless of indication 1
• Titrate cautiously to maximum 40 mg daily as tolerated 1
• Significant drug accumulation occurs at this level of renal impairment 3, 4
• Effective half-life triples compared to normal renal function 2
• Peak concentrations are higher and time to peak is extended 2

Monitoring Requirements

Initial Monitoring

• Check renal function and serum potassium within 1-2 weeks of initiation or dose increase 5
• Baseline assessment before starting therapy is essential 5

Ongoing Monitoring

• Renal function tests every 3 months during chronic therapy if on ACE inhibitors 5
• More frequent monitoring (days to 2 weeks) when making dose adjustments 5
• Minimum 6-monthly monitoring for stable patients 5

Critical Thresholds

• Discontinue if potassium ≥6 mmol/L 5
• Reduce dose if serum creatinine increases >30% or eGFR decreases >25% from baseline 5
• If lesser degree of renal deterioration occurs, recheck in 1-2 weeks but do not reduce dose unless above thresholds are exceeded 5

Clinical Pharmacology Considerations

Drug Accumulation

• Lisinopril accumulation is highly correlated with creatinine clearance 2
• Steady state is achieved in 2-3 days with normal renal function, but accumulation occurs with CrCl ≤30 mL/min 3
• Despite accumulation in severe renal failure, excessive antihypertensive effects do not necessarily occur 4

Efficacy in Renal Impairment

• Blood pressure reduction occurs across all levels of renal function over 24 hours 2, 4
• ACE activity is suppressed to <10% of baseline from 4-24 hours after dosing in all renal function groups 4
• Proteinuria may decrease with appropriate dosing (e.g., from 3.9 to 2.7 g per 24 hours) 6
• Overall GFR typically remains stable during treatment when appropriately dosed 7

Important Caveats

Hyperkalemia Risk

• Risk increases with concomitant use of higher ACE inhibitor doses (lisinopril ≥10 mg daily) 5
• Avoid potassium supplements or reduce them when initiating lisinopril 5
• Avoid NSAIDs and COX-2 inhibitors which increase hyperkalemia risk 5
• Risk is particularly elevated in patients with diabetes requiring insulin 5

Hypotension Management

• If systolic BP drops to ≤100 mmHg, reduce to 5 mg daily maintenance dose 1
• If prolonged hypotension occurs (systolic BP <90 mmHg for >1 hour), withdraw lisinopril 1
• Initial hypotension does not preclude careful subsequent titration after effective hypotension management 1

Pediatric Considerations

• Not recommended in children <6 years or with GFR <30 mL/min/1.73m² 1
• For children ≥6 years with GFR >30 mL/min/1.73m²: start at 0.07 mg/kg once daily (maximum 5 mg), titrate to maximum 0.61 mg/kg (up to 40 mg) once daily 1