Renal and Vascular Protective Effects of Ezetimibe in Chronic Kidney Disease

Abstract

Objective Dyslipidemia is a risk factor for not only cardiovascular diseases (CVD), but also chronic kidney disease (CKD). Ezetimibe, a cholesterol absorption inhibitor, lowers cholesterol levels by inhibiting both extrinsic and intrinsic cholesterol absorption via the gastrointestinal duct. However, very few studies have examined its efficacy and safety for patients with dyslipidemia complicated with CKD. Methods Thirty-seven dyslipidemic patients (low density lipoprotein cholesterol (LDL-C) levels ! 120 mg/ dL) complicated with CKD were given ezetimibe (10 mg/day) for twenty-four weeks. The efficacy and safety of the therapy, including the anti-atherosclerotic and renal protective effects, were then examined. Results Significant decreases were observed in the levels of LDL-C (158.9±26.9 mg/dL 123.0±31.8 mg/ dL; p<0.0001), remnant-like lipoprotein cholesterol (9.3±5.3 mg/dL 7.3±3.8 mg/dL; p<0.05) and lipoprotein (a) (22.0±16.1 mg/dL 16.4±11.0 mg/dL; p<0.01). The estimated glomerular filtration rate did not change, but the urine protein to creatinine ratio decreased significantly (1,107.3±1,454.2 mg/gCre 732.1±1,237.8 mg/gCre; p<0.05). No changes were observed in the carotid intima media thickness, but the brachial-ankle pulse wave velocity decreased significantly (1,770.4±590.3 cm/sec 1,702.5±519.9 cm/sec; p<0.05). No adverse events were observed. Conclusion Ezetimibe can be safely administered even to patients with CKD. The results of this study indicate that ezetimibe may provide some renal protection and suppress the complications of CVD in CKD patients.

Multiple potency of ezetimibe in a patient with macroproteinuric chronic kidney disease and statin-intolerant dyslipidemia

“…Morita et al [3] have also reported that ezetimibe can be administered safely to CKD patients, and that it improved lipid profiles and decreased proteinuria and arterial stiffness. Ezetimibe may lower proteinuria and urinary L-FABP levels and improve vascular function via its lipid-lowering action, although the actual mechanisms remain to be clarified.…”

Effects of atorvastatin on renal function in patients with dyslipidemia and chronic kidney disease: assessment of clinical usefulness in CKD patients with atorvastatin (ASUCA) trial

“…In turn, 79 % of patients in Group C had been administered ezetimibe. Since ezetimibe would have renal protective effect [17, 18], it is likely that ezetimibe might be reno-protective as much as atorvastatin in this study [19, 20]. …”

Management of dyslipidaemia in patients with chronic kidney disease: a position paper endorsed by the Italian Society of Nephrology

“…The Table 3 describes the effects of ezetimibe and the treatment indications for patients with renal disease. According to KDIGO guidelines [37], ezetimibe monotherapy is not recommended in CKD patients since there is only scarce evidence of its effectiveness on relevant clinical outcomes [103,104]. Conversely, mainly based on the results of the randomised double-blind SHARP (Study of Heart and Renal Protection) trial [33], the use of statin/ ezetimibe association is formally recommended in predialysis CKD patients (see above and Table 2).…”