Is ezetimibe (Zetia) safe to use in a patient with acute kidney injury (AKI) and a history of hypertension?

Ezetimibe Safety in Acute Kidney Injury

Ezetimibe is safe to use in patients with acute kidney injury and does not require dose adjustment, as it is primarily eliminated through fecal excretion rather than renal clearance. 1

Pharmacokinetic Profile in Renal Impairment

• No dosage adjustment of ezetimibe is necessary in patients with renal impairment, including those with AKI. 1
• Approximately 78% of ezetimibe is excreted in feces predominantly as parent drug, with only the balance found in urine mainly as ezetimibe-glucuronide, making renal function largely irrelevant to drug clearance. 2
• The terminal half-life of ezetimibe and its active metabolite is approximately 22 hours, which remains stable regardless of kidney function. 2

Evidence in Chronic Kidney Disease Populations

• In the IMPROVE-IT trial subgroup analysis of patients with reduced kidney function (eGFR 30-60 ml/min per 1.73 m²), ezetimibe plus simvastatin showed greater cardiovascular benefit compared to simvastatin alone, with a 12-13% risk reduction in major adverse cardiovascular events. 3
• Ezetimibe administered at 10 mg/day for 24 weeks in 37 dyslipidemic CKD patients demonstrated significant reductions in LDL-C (from 158.9 to 123.0 mg/dL) without adverse events, and the estimated GFR remained stable throughout treatment. 4
• The Study of Heart and Renal Protection (SHARP) trial demonstrated a 25% reduction in ischemic stroke in CKD patients treated with simvastatin plus ezetimibe, establishing safety and efficacy in this population. 5

Clinical Application in AKI Context

• Ezetimibe should be continued or initiated during AKI episodes without concern for drug accumulation or toxicity. 1
• Unlike ACE inhibitors, ARBs, diuretics, and NSAIDs—which should be held during AKI to prevent worsening prerenal azotemia—ezetimibe does not affect renal hemodynamics or intravascular volume. 6
• The 2024 KDIGO CKD guidelines recommend ezetimibe as add-on therapy to statins based on ASCVD risk and lipid levels, with no contraindications related to kidney function. 5

Guideline-Supported Use

• The 2024 ACC/AHA peripheral artery disease guideline assigns a Class 1 recommendation for ezetimibe in patients with PAD who have not achieved LDL-C <70 mg/dL on statin therapy, with no restrictions based on renal function. 5
• The 2025 ACC/AHA acute coronary syndrome guideline notes that ezetimibe added to simvastatin reduced MACE by 6.4% in the IMPROVE-IT trial, with benefit observed regardless of baseline renal function. 5
• KDOQI commentary on KDIGO lipid guidelines supports continuation of statin/ezetimibe therapy in dialysis patients who were already receiving it prior to dialysis initiation, demonstrating safety even in advanced kidney disease. 5

Practical Considerations

• Ezetimibe can be administered at any time of day without regard to food, making it practical during acute illness when oral intake may be variable. 2
• The only clinically significant drug interaction is with cholestyramine, which decreases ezetimibe bioavailability and should be administered several hours apart. 2
• In patients with hypertension and AKI, focus nephroprotective efforts on holding ACE inhibitors, ARBs, and diuretics temporarily while maintaining cardiovascular risk reduction with ezetimibe. 5, 6

Additional Renoprotective Effects

• Beyond lipid lowering, ezetimibe decreased proteinuria (from 1,107.3 to 732.1 mg/gCre) in CKD patients over 24 weeks, suggesting direct renal protective effects independent of cholesterol reduction. 4
• Ezetimibe reduced serum asymmetric dimethylarginine (ADMA) levels and urinary markers of oxidative stress in non-diabetic CKD patients, indicating pleiotropic renoprotective properties. 7