Ezetimibe/Simvastatin Combination in Proteinuric Nephropathy
Ezetimibe/Simvastatin Combination in Proteinuric Nephropathy
The purpose of this study is to determine whether, in patients with chronic proteinuric
 nephropathy and dyslipidemia, ezetimibe-simvastatin combined therapy is more effective than
 statin alone to achieve the optimum lipid control, and if this translates to an improvement
 of the markers of vascular damage. Thirty hypertensive patients in stable therapy with RAS
 inhibitors, with low-density lipoprotein (LDL) cholesterol superior to 100 mg/ml, are treated
 with three different hypolipidemic regimens: Simvastatin alone (40 mg/day) or
 ezetimibe/simvastatin combined therapy (10/20 or 10/40 mg/day).
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.
Inclusion Criteria:

 -  age >18 years

 -  LDL-cholesterol > 100 mg/dl (without concomitant hypolipidemic drugs) in patients whit
 high cardiovarscular risk for the concomitant presence of:

 -  proteinuric chronic nephropathy defined as creatinine clearance > 20 ml/min/1,73 m2
 combined to a urinary protein excretion rate > 0,3 g/24h, without evidence of urinary
 tract infection or overt heart failure (New York Heart Association class III or more)

 -  hypertension defined as a systolic or diastolic blood pressure > 140 or 90 mmHg
 respectively (or less in patients with concomitant antihypertensive therapy)

 Exclusion Criteria:

 -  previous or concomitant treatment with steroids, anti-inflammatory and
 immunosuppressive agents

 -  evidence or suspicion of renovascular disease, obstructive uropathy, type I diabetes
 mellitus, vasculitides, history of poor tolerance or allergy to ACEi and ATA, statin
 or EZE, drug abuse or pregnancy

 -  inability to fully understand the purposes/risks of the study and to provide a written
 informed consent