Zetia (Ezetimibe) Does Not Adversely Affect Renal Function
No dose adjustment of ezetimibe is necessary in patients with renal impairment, and the drug does not harm kidney function. 1
Pharmacokinetic Evidence in Renal Impairment
The FDA label explicitly states that no dosage adjustment is required for patients with any degree of renal impairment 1. In patients with severe renal disease (CrCl ≤30 mL/min/1.73 m²), ezetimibe exposure (AUC) increased only approximately 1.5-fold compared to healthy subjects—a modest increase that is not clinically significant and does not necessitate dose modification 1.
- Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation, with subsequent biliary and renal excretion 1
- Only approximately 11% of the administered dose is recovered in urine, while 78% is excreted in feces 1
- This predominantly non-renal elimination pathway explains why kidney dysfunction has minimal impact on drug clearance 1
Guideline-Based Use in CKD Populations
Ezetimibe is explicitly recommended for use in patients with chronic kidney disease, either as monotherapy or combined with statins:
- KDIGO guidelines (Grade 1A) recommend statin or statin/ezetimibe combination for adults ≥50 years with eGFR <60 mL/min/1.73 m² (CKD stages 3a-5) not on dialysis 2, 3
- ESC/EAS 2016 guidelines (Grade 1A) indicate that statin/ezetimibe combination is appropriate for non-dialysis-dependent CKD patients 2
- The landmark SHARP trial demonstrated that simvastatin-ezetimibe combination reduced major atherosclerotic events in CKD patients (stages 3a-5), providing Level 1A evidence for safety and efficacy 2
Evidence of Renoprotective Effects
Emerging research suggests ezetimibe may actually provide renal protection rather than harm:
- In a study of 37 CKD patients treated with ezetimibe for 24 weeks, the urine protein-to-creatinine ratio decreased significantly (1,107.3→732.1 mg/gCre, p<0.05) while eGFR remained stable 4
- Co-administration of ezetimibe with pitavastatin produced incremental reduction in proteinuria beyond statin therapy alone in non-diabetic CKD patients 5
- In kidney transplant recipients, ezetimibe treatment for 12 months maintained stable creatinine clearance while control patients experienced significant decline (delta Cockcroft-Gault: 0.9 vs -4.8 mL/min, p=0.025) 6
Special Population: Dialysis Patients
The only CKD population where ezetimibe initiation is not recommended is dialysis-dependent patients without pre-existing atherosclerotic CVD 2. However, this recommendation is based on lack of proven cardiovascular benefit in this specific population, not due to safety concerns or adverse effects on renal function 2.
- If patients are already receiving ezetimibe at the time of dialysis initiation, continuation is suggested (Grade 2C), particularly in those with CVD 2
Kidney Transplant Recipients
Ezetimibe is safe and effective in kidney transplant recipients:
- Treatment with ezetimibe may be considered in adult kidney transplant recipients (Grade 2B) 2
- Multiple studies demonstrate efficacy and safety in this population, with no adverse effects on renal function or immunosuppressive drug levels 7, 6
- Renal function remained stable with no significant variations in plasma levels of immunosuppressive agents 7
Critical Implementation Points
Ezetimibe can be safely prescribed across the spectrum of CKD severity without dose adjustment 1. The only contraindication relates to moderate-to-severe hepatic impairment (Child-Pugh B or C), not renal impairment 1. When used in combination with statins in CKD patients, attention should be paid to statin dosing requirements (which may need adjustment based on renal function), but ezetimibe itself requires no modification 2, 3, 8.