Ezetimibe/Simvastatin Combination in Proteinuric Nephropathy

Patients with chronic kidney disease (CKD) have an increased incidence of cardiovascular morbidity and mortality. Presence of hypertension, lipid abnormalities and inflammation each contribute to increased cardiovascular risk. Therefore blood pressure control slows the progression of CKD towards End Stage Renal Failure (ESRF) improving clinical outcome. Instead the contribution of lipid abnormalities is still not completely understood, mainly because dyslipidemia interferes with a number of non-traditional cardiovascular risk factors, particularly the activated acute-phase response. In proteinuric patients, dyslipidemia has a highly atherogenic profile, with increased total and low-density lipoprotein (LDL) cholesterol, triglyceride, and lipoprotein(a) serum levels, as well as decreased HDL cholesterol. Numerous studies have indicated that treatment of dyslipidemia with a statin decreases cardiovascular morbidity and mortality. Experimental and clinical evidences show that statin, in addition to ameliorate lipid profile, may have specific renoprotective properties and, combined to Renin-Angiotensin System (RAS) inhibitor therapy, may synergize their antiproteinuric effects. Preliminary data are also available data that the combination of statin to ezetimibe (EZE), a cholesterol absorption inhibitor, produces an additional decrease in LDL cholesterol and C-reactive protein levels, over that achieved with statin monotherapy. Thus, adding the potential antinflammatory effect to hypolipidemic efficacy, combined therapy may expand the renal and cardioprotective potentiality. It may also permit a reduction of statin therapeutic dose improving safety profile. Therefore EZE-statin combination therapy may be an effective therapeutic option to statin alone in patients with high cardiovascular risk, such as chronic proteinuric patients.