What are the guidelines for using losartan (angiotensin II receptor antagonist) in patients with acute kidney injury (AKI)?

Losartan and Acute Kidney Injury

Primary Recommendation

Losartan must be discontinued immediately when acute kidney injury occurs, as ARBs directly compromise renal hemodynamics by blocking angiotensin II receptors, which decreases glomerular filtration pressure and can precipitate acute renal failure in patients with already impaired kidney function. 1, 2

Mechanism of Harm in AKI

• Losartan blocks angiotensin II AT1 receptors, eliminating the compensatory efferent arteriolar vasoconstriction that maintains glomerular filtration pressure when renal perfusion is compromised 1, 3
• The FDA label explicitly warns that "changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system" 2
• Patients whose renal function depends on the renin-angiotensin system (volume depletion, severe heart failure, renal artery stenosis) are at particular risk of developing acute renal failure on losartan 2

High-Risk Clinical Scenarios Requiring Immediate Discontinuation

Losartan should be stopped in the following situations: 1, 2

• Any documented AKI episode (rising creatinine, decreased urine output)
• Volume depletion from high-dose diuretics 4
• Severe congestive heart failure with compromised renal perfusion 3, 4
• Bilateral renal artery stenosis or unilateral stenosis in a solitary kidney 3, 4, 5
• Intercurrent acute illness with hemodynamic instability 1
• Planned procedures: IV radiocontrast administration, bowel preparation, major surgery 1

Critical Case Evidence

• A 70-year-old patient with a solitary kidney developed two episodes of transient anuria lasting 8-10 hours after receiving just 50 mg of losartan, despite high-dose furosemide and vasopressor support 4
• Multiple case reports document reversible acute renal failure with losartan in patients with underlying renal pathology, with identical incidence rates to ACE inhibitors (10.5% in elderly heart failure patients) 3

Alternative Antihypertensive Agents During AKI

Use these agents instead of losartan during the acute phase: 1

• Dihydropyridine calcium channel blockers (amlodipine 2.5-10 mg daily) - minimal effects on renal hemodynamics 1
• Loop diuretics (furosemide) for volume overload with moderate-to-severe kidney dysfunction 1
• Beta-blockers if concomitant ischemic heart disease or heart failure exists 1
• Thiazide-like diuretics only in mild-moderate AKI (GFR >30 mL/min) 1

Protocol for Restarting Losartan After AKI Resolution

Do not restart losartan until ALL of the following criteria are met: 1

Prerequisites for Reintroduction:

• GFR has stabilized (not just improved, but stable over multiple measurements) 1
• Volume status is optimized (euvolemic, not volume depleted) 1
• Acute illness has completely resolved 1
• Mean arterial pressure >65 mmHg 1
• Serum potassium <5.5 mEq/L 1

Reintroduction Protocol:

• Start with lower doses than previously used 1
• Titrate slowly while monitoring renal function 1
• Check serum creatinine and potassium within 1 week of restarting 1
• Accept a creatinine increase of 10-20% as tolerable; suspend if greater 1

Absolute Contraindications to Restarting

Never restart losartan if: 1, 2

• Serum potassium remains >5.5 mEq/L 1
• Patient is on dual RAS blockade (ACE inhibitor + ARB, or aliskiren + ARB) - the VA NEPHRON-D trial showed increased hyperkalemia and acute kidney injury with combination therapy without additional benefit 2
• Patient has diabetes and is on aliskiren 2
• Bilateral renal artery stenosis or unilateral stenosis in solitary kidney 3, 4

Drug Interactions That Worsen AKI Risk

Avoid these combinations with losartan, especially during or after AKI: 2

• NSAIDs (including COX-2 inhibitors) - can cause acute renal failure in elderly, volume-depleted, or renally compromised patients 2
• Potassium-sparing diuretics or potassium supplements - substantially increases hyperkalemia risk 1, 2
• Other RAS inhibitors (ACE inhibitors, aliskiren) - increases acute kidney injury risk 2

Monitoring Requirements

If losartan is restarted after AKI, monitor: 1, 2

• Serum creatinine within 1 week, then periodically 1
• Serum potassium within 1 week, then periodically 1, 2
• Blood pressure to avoid hypotension 1
• Consider withholding or permanently discontinuing if clinically significant decrease in renal function develops 2

Long-Term Perspective After AKI Recovery

• Important caveat: While losartan must be stopped during AKI, observational data suggests that continuing ARBs after complete AKI recovery is associated with reduced mortality and cardiovascular events without increased recurrent AKI risk 1
• Animal studies show losartan may reduce progression to CKD after functional recovery from AKI, but this applies only after complete recovery, not during the acute phase 6
• The KDIGO guidelines identify the need for more research on optimal timing of ARB discontinuation and reintroduction, but current evidence supports temporary suspension during AKI with potential reintroduction after stabilization 1