When can Lisinopril (Zestril) be initiated in a patient with Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD)?

From the Guidelines

Lisinopril should be restarted in AKI on CKD only after the acute kidney injury has resolved and renal function has stabilized, typically when serum creatinine returns to baseline or near-baseline levels, as suggested by the most recent guidelines 1. When considering the restart of Lisinopril, it is crucial to assess the patient's volume status and ensure they are euvolemic and hemodynamically stable, with no ongoing nephrotoxic insults.

• The patient should be monitored closely for signs of renal function deterioration or hyperkalemia.
• Restarting with a lower dose, such as 2.5-5 mg daily, and titrating gradually is recommended, with close monitoring of renal function and potassium levels, checking labs within 1-2 weeks after initiation 1.
• It is essential to avoid restarting Lisinopril if the patient has severe hyperkalemia (K+ >5.5 mEq/L), hypotension (systolic BP <90 mmHg), or if the AKI was potentially caused by ACE inhibitor use (such as in bilateral renal artery stenosis) 1. The caution with ACE inhibitors in AKI stems from their mechanism of action, which can decrease glomerular filtration pressure and potentially worsen kidney function in vulnerable patients, particularly those with volume depletion or renal artery stenosis.
• The risk-benefit ratio of restarting ACE inhibitors like Lisinopril in patients with AKI on CKD must be carefully considered, and therapy should be personalized according to the individual risks of the patient 1.

From the FDA Drug Label

1. 3 Impaired Renal Function Monitor renal function periodically in patients treated with lisinopril. Changes in renal function including acute renal failure can be caused by drugs that inhibit the renin-angiotensin system. 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, post-myocardial infarction or volume depletion) may be at particular risk of developing acute renal failure on lisinopril. Consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function on lisinopril [see Adverse Reactions (6. 1), Drug Interactions (7.4)].

The FDA drug label does not provide a specific guideline on when to start Lisinopril in patients with Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD). Key considerations for using Lisinopril in patients with impaired renal function include:

• Monitoring renal function periodically
• Being aware of the potential risk of acute renal failure
• Considering withholding or discontinuing therapy if a clinically significant decrease in renal function occurs 2

From the Research

Timing of Lisinopril Initiation in AKI on CKD

• The decision to start Lisinopril in patients with Acute Kidney Injury (AKI) on Chronic Kidney Disease (CKD) depends on various factors, including the severity of AKI and CKD, as well as the presence of other comorbidities 3.
• According to a study published in 2025, early use of Angiotensin-Converting Enzyme Inhibitors (ACEi) or Angiotensin Receptor Blockers (ARBs) post-AKI was not associated with better long-term survival or kidney function, but was associated with lower mortality in patients with KDIGO 3 AKI 3.
• However, another study published in 2011 suggests that ACE inhibitors and ARBs can be detrimental in CKD patients, particularly in older hypertensive patients, and that their use should be approached with caution 4.
• It is also important to note that ACE inhibitors can cause renal insufficiency in some patients, particularly those with underlying critical renal artery stenosis, hypertensive nephrosclerosis, or chronic congestive heart failure 5.
• The definition and treatment of AKI have been standardized by the Kidney Disease: Improving Global Outcomes (KDIGO) group, which provides guidelines for the diagnosis and management of AKI 6.

Considerations for Lisinopril Initiation

• Before initiating Lisinopril in patients with AKI on CKD, it is essential to assess the patient's renal function, blood pressure, and electrolyte levels 7.
• The patient's medical history, including the presence of other comorbidities, such as heart failure or diabetes, should also be considered 3.
• The potential risks and benefits of Lisinopril use in patients with AKI on CKD should be carefully weighed, and the decision to initiate therapy should be made on an individual basis 4.