Should losartan (Angiotensin II Receptor Antagonist) be held in the setting of Acute Kidney Injury (AKI)?

From the Guidelines

Yes, losartan should typically be held in the setting of acute kidney injury (AKI). As an angiotensin II receptor blocker (ARB), losartan can worsen kidney function during an AKI episode by reducing glomerular filtration pressure. When a patient develops AKI, temporarily discontinuing losartan allows the kidneys to maintain adequate filtration pressure, which may help stabilize or improve kidney function. This is particularly important in cases where volume depletion, hypotension, or nephrotoxic insults are contributing to the AKI. The medication can be resumed once kidney function stabilizes and returns to baseline, typically indicated by normalization of creatinine levels. During this period, blood pressure should be monitored and managed with alternative agents if necessary. The decision to restart losartan should be made in consultation with a nephrologist or primary physician, who can evaluate the risk-benefit ratio based on the patient's underlying conditions such as heart failure or proteinuric kidney disease, where ARBs provide significant long-term benefits despite the short-term risks during AKI.

Key Considerations

• The decision to discontinue, introduce, and/or reintroduce medications in patients with AKI should be individualized, considering factors such as renal versus non-renal excretion, potential for nephrotoxicity, and the strength of indications for the drug 1.
• The risk-benefit ratio of using ACE inhibitors and ARBs in patients with AKI is not well established, and the decision to stop or restart these medications should be made on a case-by-case basis 1.
• Alternative agents for managing blood pressure during AKI may include diuretics, calcium channel blockers, or other antihypertensive medications, which can be selected based on the patient's underlying conditions and the presence of any contraindications 1.

Management Approach

• Temporarily discontinue losartan in patients with AKI to minimize the risk of worsening kidney function.
• Monitor blood pressure closely and manage with alternative agents as needed.
• Resume losartan once kidney function stabilizes and returns to baseline, in consultation with a nephrologist or primary physician.
• Consider the patient's underlying conditions, such as heart failure or proteinuric kidney disease, when evaluating the risk-benefit ratio of restarting losartan.

From the FDA Drug Label

5.3 Renal Function Deterioration Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system and by diuretics. Patients whose renal function may depend in part on the activity of the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure on losartan. Monitor renal function periodically in these patients Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan

Losartan should be held in the setting of Acute Kidney Injury (AKI), as the drug label recommends considering withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on losartan 2 2.

From the Research

Losartan and Acute Kidney Injury (AKI)

• Losartan, an Angiotensin II Receptor Antagonist, may cause acute renal failure in patients sensitive to reduced renal plasma flow, such as those with bilateral renal artery stenosis, severe congestive heart failure, and severe sodium and volume depletion 3.
• The ELITE trial showed a 10.5% incidence of losartan-induced renal dysfunction in elderly patients with congestive heart failure with no known underlying renal dysfunction, similar to that of captopril 3.
• A study found that discontinuation or dose reduction of diuretics or neurohormonal blockers, including ACE-Is/ARBs like losartan, may improve renal outcome at the price of less efficient decongestion in patients with acute heart failure and AKI 4.

Management of Losartan in AKI

• There is no evidence to suggest that losartan is better tolerated than ACE inhibitors from the standpoint of renal toxicity, and it should be avoided in patients with bilateral renal artery stenosis and in patients with unilateral renal artery stenosis in a solitary kidney 3.
• In patients with underlying renal dysfunction, losartan may be used if deemed necessary, but renal function should be monitored, and losartan should be stopped if evidence of renal dysfunction becomes apparent 3.
• A systematic review and meta-analysis found that exposure to ACEi/ARB, including losartan, after AKI is associated with lower risks of all-cause mortality, recurrent AKI, and progression to incident CKD, but with a higher incidence of hyperkalemia 5.

Case Reports and Studies

• A case report described a renal transplant recipient who developed reversible acute renal failure induced by losartan, which was resolved after withdrawal of the medication 6.
• Another study discussed the role of medications and their management in AKI, highlighting the importance of identifying the likely location of injury and adjusting medication doses accordingly 7.