Why is it important to stop losartan (angiotensin II receptor antagonist) in patients with acute kidney injury (AKI)?

Why Losartan Should Be Discontinued in Acute Kidney Injury

Losartan and other angiotensin II receptor blockers (ARBs) should be discontinued immediately in patients with acute kidney injury (AKI) as they can exacerbate kidney dysfunction by reducing glomerular filtration pressure, potentially worsening outcomes and delaying recovery. 1

Mechanism of ARB-Induced Kidney Dysfunction in AKI

• ARBs like losartan directly affect renal hemodynamics by blocking angiotensin II receptors, which decreases glomerular filtration pressure and can further compromise already impaired kidney function in AKI patients 1
• The FDA drug label for losartan specifically warns that "changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system" 2
• In patients with AKI, renal function may depend on the activity of the renin-angiotensin system to maintain adequate filtration pressure, making them particularly vulnerable to ARB-induced worsening of kidney function 2

Evidence Supporting Discontinuation

• The American College of Cardiology and other guideline societies recommend avoiding ARBs in patients with AKI as they can exacerbate kidney dysfunction and increase the risk of progression to acute kidney disease (AKD) 1
• The Kidney Disease: Improving Global Outcomes (KDIGO) conference specifically identified the need for research on "timing of ACE-I/ARBs discontinuation and re-initiation in AKI/AKD in different clinical contexts" highlighting the importance of this clinical decision 3
• Multiple case reports have documented reversible acute renal failure following losartan administration, particularly in patients with underlying renal dysfunction or risk factors 4, 5

High-Risk Scenarios for ARB Use in AKI

• Patients with volume depletion or salt depletion are at particularly high risk, as the FDA label warns that "symptomatic hypotension may occur after initiation of treatment with losartan" in these patients 2
• Patients with bilateral renal artery stenosis, severe heart failure, or those on diuretic therapy are especially vulnerable to ARB-induced kidney dysfunction 4, 6
• Elderly patients with congestive heart failure showed a 10.5% incidence of losartan-induced renal dysfunction, even without known underlying renal dysfunction 4

Management Recommendations

• The FDA label explicitly recommends to "consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan" 2
• Alternative antihypertensive medications with less nephrotoxic potential should be used during the AKI episode, such as calcium channel blockers which have minimal effects on renal hemodynamics 1
• Reintroduction of ARBs should only be considered after GFR has stabilized and volume status is optimized 1
• The Acute Disease Quality Initiative (ADQI) workgroup recommends that drug selection in AKI should be guided by the functional phase, trajectory, and stage of kidney injury 3

Monitoring and Follow-up

• If ARBs must be used in patients at risk for AKI, renal function should be monitored closely and the medication should be stopped if evidence of renal dysfunction becomes apparent 4
• Monitor serum potassium levels as hyperkalemia is a common complication of ARB use in patients with impaired kidney function 2
• The decision to reintroduce ARBs after AKI resolution should be individualized based on the patient's underlying conditions, with careful monitoring of kidney function 3

Long-term Considerations

• Interestingly, some research suggests that losartan may reduce ensuing chronic kidney disease and mortality when administered after functional recovery from AKI, highlighting the importance of appropriate timing 7
• This paradox emphasizes why discontinuation during the acute phase of kidney injury is crucial, while consideration for reintroduction after recovery may be beneficial in selected patients 7