What is the preferred choice between lisinopril (Angiotensin-Converting Enzyme Inhibitor (ACEI)) and losartan (Angiotensin II Receptor Blocker (ARB)) for managing hypertension in an adult or geriatric patient with Acute Kidney Injury (AKI) and possible comorbidities such as diabetes or heart disease?

ACE Inhibitors and ARBs Should Be Withheld During Acute Kidney Injury

Both lisinopril (ACE inhibitor) and losartan (ARB) should be temporarily discontinued during acute kidney injury (AKI) and only restarted after kidney function has stabilized and volume status is optimized. Neither agent is preferred over the other in the setting of AKI—both carry equivalent risks of worsening renal function through efferent arteriolar vasodilation and reduced glomerular filtration pressure 1, 2, 3.

Why Both Agents Should Be Stopped in AKI

Hemodynamic Mechanisms of Harm

• Both ACE inhibitors and ARBs reduce glomerular filtration pressure by blocking angiotensin II-mediated efferent arteriolar vasoconstriction, which can precipitate or worsen AKI, particularly when renal perfusion is already compromised 1, 4.

• The risk-benefit ratio during AKI does not favor continued use of either drug class, as the acute hemodynamic effects that may be tolerable in chronic kidney disease or heart failure are not tolerable and lack proven benefit during acute kidney disease 1.

• Losartan causes the same negative renal effects as ACE inhibitors through identical mechanisms—both reduce intraglomerular pressure when filtration is critically dependent on angiotensin II-mediated tone 2, 3, 5.

Evidence Supporting Discontinuation

• The ADQI consensus guidelines explicitly state that ACE inhibitors and ARBs should be stopped during AKI, though sparse evidence exists for routine discontinuation recommendations 1.

• Case reports and clinical trials demonstrate that both losartan and ACE inhibitors can cause reversible acute renal failure, with no evidence suggesting losartan is better tolerated than ACE inhibitors from a renal toxicity standpoint 2, 3.

• Two surgical studies showed increased 30-day mortality when these agents were not restarted after surgery, possibly from hypertensive rebound leading to cardiac decompensation—but this applies to the post-recovery period, not during active AKI 1.

High-Risk Clinical Scenarios Requiring Absolute Avoidance

Contraindications During AKI

• Bilateral renal artery stenosis or unilateral stenosis in a solitary kidney: Both drug classes are contraindicated as glomerular filtration becomes critically dependent on angiotensin II-mediated efferent tone 2, 5.

• Severe volume depletion or aggressive diuresis: Patients with AKI receiving loop diuretics are at particularly high risk, as sodium depletion potentiates the hemodynamic effects of both ACE inhibitors and ARBs 3, 4.

• Severe heart failure with low cardiac output: When renal perfusion is angiotensin-dependent, both agents can precipitate acute renal failure 2, 3.

When and How to Restart After AKI Recovery

Criteria for Reinitiation

• Wait until GFR has stabilized and volume status is optimized before considering reinitiation of either agent 1.

• Monitor serum creatinine and potassium within 1-2 weeks after restarting therapy, as both agents carry equivalent risks of hyperkalemia and further renal dysfunction 1, 6.

• Accept a modest rise in serum creatinine (up to 30%) after reinitiation, as this hemodynamic effect may be associated with long-term renoprotection in chronic kidney disease—but this tolerance does not apply during active AKI 1, 4.

Monitoring Protocol Post-Restart

• Check serum creatinine and potassium within 2-4 weeks of reinitiation or dose increase 6.

• Stop immediately if creatinine continues to rise beyond 30% or if refractory hyperkalemia develops (potassium >5.5 mmol/L) 1, 6.

• Counsel patients to hold the medication during sick days or any intercurrent illness that risks volume depletion 1.

No Preference Between Lisinopril and Losartan

Equivalent Renal Toxicity Profile

• There is no evidence that losartan is better tolerated than lisinopril from a renal toxicity standpoint, whether in patients with or without underlying renal dysfunction 2.

• The ELITE trial showed identical 10.5% incidence of renal dysfunction with losartan versus captopril in elderly heart failure patients 2.

• Case reports document cross-reactivity: Patients who developed renal dysfunction on ACE inhibitors also developed it on losartan, and vice versa 2, 3.

When ARBs May Be Preferred (Outside of AKI)

• Losartan is reasonable only if ACE inhibitor is not tolerated due to cough or angioedema in patients with chronic kidney disease—but this consideration is irrelevant during active AKI when both should be stopped 1.

• Never combine ACE inhibitors and ARBs, as this increases adverse effects without additional benefit 1, 6.

Common Pitfalls to Avoid

• Do not continue either agent "because the patient has been on it chronically"—the acute setting of AKI changes the risk-benefit calculation entirely 1.

• Do not assume losartan is "safer for the kidneys"—this is a common misconception not supported by evidence 2, 3.

• Do not restart too early—wait for clear evidence of AKI recovery with stable creatinine before reintroducing either agent 1.

• Do not ignore volume status—ensure adequate hydration and avoid concurrent aggressive diuresis when restarting 1, 4.