Does Zetia (ezetimibe) affect kidney function?

Ezetimibe (Zetia) and Kidney Function

Ezetimibe (Zetia) is generally safe for patients with kidney disease and does not require dose adjustment in renal impairment, as it is primarily metabolized in the small intestine and liver with minimal impact on kidney function. 1

Pharmacokinetics and Renal Handling

Ezetimibe works by inhibiting the intestinal absorption of cholesterol at the brush border of the small intestine by targeting the Niemann-Pick C1-Like 1 (NPC1L1) protein 2, 1. After oral administration, ezetimibe is:

• Rapidly absorbed and extensively metabolized (>80%) to the pharmacologically active ezetimibe-glucuronide
• Primarily eliminated through fecal excretion (78% of the dose)
• Only minimally excreted through the kidneys (11% of the dose) 3
• Not affected by renal function in terms of dosing requirements 1

The FDA label explicitly states: "No dosage adjustment of ezetimibe tablets is necessary in patients with renal impairment." 1

Evidence in Patients with Kidney Disease

Efficacy in CKD Patients

The SHARP (Study of Heart and Renal Protection) trial provided strong evidence for ezetimibe's safety and efficacy in patients with chronic kidney disease:

• Included 9,270 patients with CKD (including those on dialysis)
• Combination of simvastatin 20 mg plus ezetimibe 10 mg reduced major atherosclerotic events by 17% compared to placebo
• No heterogeneity of effects was observed between dialysis-dependent patients and those not on dialysis
• No evidence of excess risks related to kidney function 2

Potential Renal Benefits

A small study of 37 dyslipidemic patients with CKD showed that ezetimibe treatment for 24 weeks:

• Did not change estimated glomerular filtration rate
• Significantly decreased urine protein to creatinine ratio (1,107.3 ± 1,454.2 mg/gCre → 732.1 ± 1,237.8 mg/gCre; p<0.05)
• Decreased brachial-ankle pulse wave velocity, suggesting improved vascular function
• Had no adverse events 4

Clinical Recommendations for Use in Kidney Disease

The KDOQI Clinical Practice Guideline for Diabetes and CKD recommends:

• Using LDL-C lowering medicines, such as statins or statin/ezetimibe combination, to reduce risk of major atherosclerotic events in patients with diabetes and CKD, including kidney transplant recipients 2

For patients with end-stage renal disease:

• Ezetimibe can be used in combination with statins in patients with CKD, including those on dialysis 5
• The SHARP trial showed consistent results in the dialysis subgroup, reinforcing the safety of ezetimibe in this population 2

Monitoring and Precautions

While ezetimibe is generally safe in kidney disease, standard monitoring is recommended:

• Regular lipid profile assessment to evaluate treatment efficacy
• Monitoring for potential drug interactions, particularly with cyclosporine in transplant patients 3
• No specific kidney function monitoring is required due to ezetimibe use alone

Conclusion

Ezetimibe does not adversely affect kidney function and does not require dose adjustment in patients with renal impairment. In fact, some evidence suggests it may provide renal protective effects by reducing proteinuria in CKD patients 4. It represents a safe option for lipid management in patients with kidney disease, particularly when used as adjunctive therapy with statins to achieve target LDL-C levels.