What are the considerations for using lisinopril (angiotensin-converting enzyme inhibitor) in patients with acute kidney injury (AKI)?

Lisinopril Management in Acute Kidney Injury

Lisinopril should be withheld or discontinued in patients with acute kidney injury (AKI) due to its hemodynamic effects on renal function, which can worsen kidney dysfunction and precipitate acute renal failure. 1

Mechanism of Harm in AKI

Lisinopril and other ACE inhibitors cause kidney dysfunction through altered intraglomerular hemodynamics by blocking angiotensin II formation, which dilates the efferent arteriole and decreases glomerular filtration pressure. 2 This hemodynamic effect is particularly problematic in AKI where renal perfusion is already compromised. 1

Patients whose renal function depends on the renin-angiotensin system are at particular risk of developing acute renal failure on lisinopril, including those with:

• Renal artery stenosis 1
• Chronic kidney disease 1
• Severe congestive heart failure 1
• Post-myocardial infarction 1
• Volume depletion 1

When to Discontinue Lisinopril

Discontinue lisinopril immediately when:

• A patient develops AKI and lisinopril is identified as a potential causative agent 2
• There is a clinically significant decrease in renal function 1
• The patient has known risk factors for kidney injury (advanced age, previous AKI episodes, chronic kidney disease, diabetes, proteinuria, hypertension) 3
• A suitable and less nephrotoxic alternative antihypertensive is available 2, 3

The FDA label explicitly states to "consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril." 1

Alternative Antihypertensive Options During AKI

Use these alternatives instead of lisinopril during the acute phase:

• Dihydropyridine calcium channel blockers (amlodipine 2.5-10 mg daily) have minimal effects on renal hemodynamics and are preferred 3
• Loop diuretics (furosemide) for patients with volume overload and moderate-to-severe kidney dysfunction 3
• Beta-blockers if concomitant ischemic heart disease or heart failure is present 3
• Thiazide-like diuretics only in mild-moderate AKI (GFR >30 mL/min) 3

Reintroduction Protocol After AKI Resolution

Reintroduce lisinopril only after ALL of the following criteria are met:

1. GFR has stabilized and volume status is optimized 2, 3
2. Mean arterial pressure >65 mmHg to avoid symptomatic hypotension 3
3. Serum potassium <5.5 mEq/L 3
4. Acute illness has resolved 3

When restarting:

• Begin with lower doses than previously used 3
• Titrate slowly while monitoring renal function 3
• Monitor GFR and serum potassium within 1 week of restarting 3
• Accept a serum creatinine increase of 10-20% as normal 3

Critical Monitoring Requirements

Monitor the following parameters periodically in all patients on lisinopril: 1

• Renal function (serum creatinine, GFR) 1
• Serum potassium levels 1
• Blood pressure 1

The FDA label emphasizes that "changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system." 1

Special Contraindications

Never combine lisinopril with:

• Other ACE inhibitors 3
• Direct renin inhibitors 3
• Potassium supplements or potassium-sparing diuretics (substantially increased risk of hyperkalemia) 3, 1

Avoid lisinopril in patients who are:

• Hemodynamically unstable 1
• Undergoing dialysis with high-flux membranes (risk of anaphylactoid reactions) 1
• Volume depleted or hypotensive 1

Common Pitfalls to Avoid

The most critical error is continuing lisinopril during AKI based on its long-term renoprotective benefits in chronic kidney disease. 2 While ACE inhibitors are nephroprotective in stable CKD, this benefit does not apply during acute kidney injury where hemodynamic effects predominate and can worsen outcomes. 2

Another pitfall is failing to recognize that lisinopril accumulates in severe renal failure, requiring dose adjustment or discontinuation. 4 Even though high serum concentrations may not cause excessive antihypertensive effects, they increase the risk of hyperkalemia and further renal dysfunction. 4

The risk-benefit calculation fundamentally changes in AKI: the immediate risk of worsening kidney function outweighs any theoretical long-term benefit. 2, 3