Potential Benefit of Statin Therapy for Dyslipidemia with Chronic Kidney Disease: Fluvastatin Renal Evaluation Trial (FRET)

摘要

Background Dyslipidemia is a common complication of chronic kidney disease (CKD) and contributes to cardiovascular morbidity and mortality of CKD patients. Aim The aim of the present study was to determine whether fluvastatin, which is mostly characterized by its pleiotropic anti-oxidant effects, has renoprotective effects in dyslipidemic patients with CKD. Methods In 43 dyslipidemic patients with CKD taking fluvastatin 10 mg/day, 20 mg/day or 30 mg/day, renal functions as well as lipid profiles were assessed. Results After 3 months of treatment with fluvastatin, LDL-cholesterol level significantly decreased. Serum creatinine level, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), urinary liver-type fatty acid binding protein (L-FABP) level and urinary 8-hydroxydeoxyguanosine (8-OHdG) level did not change in overall patients. However, in patients with microalbuminuria (baseline UAE≥30 mg/g·creatinine; n=23), the UAE significantly decreased [2.43±0.67 to 1.98±0.80 log(mg/g·creatinine), p=0.01]. In patients with high L-FABP group (baseline L-FABP≥11 μg/g·creatinine; n=18), the urinary L-FABP level was significantly decreased (1.52±0.45 to 1.26±0.43 μg/g·creatinine, p<0.01). In the limited 23 patients with microalbuminuria, the L-FABP level was significantly decreased [1.20±0.62 to 1.03±0.49 log(μg/g·creatinine), p=0.042], although the LDL-cholesterol level (139±28 to 129±23 mg/dL, p=0.08) only showed a tendency to decrease. The 8-OHdG level also was significantly decreased (13.6±9.6 to 9.8±3.8 ng/g·creatinine, p=0.043). In the overall patients, changes in the values for UAE and urinary L-FABP were not correlated with the changes in LDL-levels. Conclusion Fluvastatin reduces both UAE and the urinary L-FABP level, and thus, has renoprotective effects, independent of its lipid lowering effects in dyslipidemic patients with CKD.