Effects of atorvastatin versus probucol on low-density lipoprotein subtype distribution and renal function in hyperlipidemic patients with nondiabetic nephropathy.

Objectives: Small dense low-density lipoprotein (LDL) plays an important role in glomerular injury through conversion to an oxidatively modified form of LDL. However, few studies have evaluated the effects of antilipidemic agents on the LDL particle size and renal function in hyperlipidemic patients with nondiabetic nephropathy. Methods: This study was a randomized crossover trial comparing the effects of atorvastatin (10 mg/day) and probucol (500 mg/day) administered for 24 weeks in 31 patients (urinary albumin excretion 0.3-2.0 g/day and creatinine clearance > 30 mL/min/1.73 m(2)). Lipid parameters, mean LDL particle diameter, creatinine clearance, and urinary albumin to creatinine excretion ratio were measured before and during treatment periods. Main findings: Atorvastatin and probucol significantly reduced the serum total cholesterol and LDL cholesterol concentrations. When stratified by mean baseline LDL particle size at 25.5 nm, atorvastatin increased (p < 0.05) LDL particle size from 24.6 +/- 0.5 to 25.2 +/- 0.9 nm only in the <25.5 nm (pattern B) group, whereas probucol decreased (p < 0.05) LDL size from 24.8 +/- 0.9 to 24.2 +/- 0.9 nm in the pattern B group and from 25.9 +/- 0.5 to 24.6 +/- 0.8 nm in the >= 25.5 nm (pattern A) group. No significant differences in urinary albumin/creatinine excretion ratio and creatinine clearance were observed in both groups during treatment. Conclusions: Only atorvastatin improved the LDL-subtype distribution in hyperlipidemic patients with nondiabetic nephropathy, although both agents exhibited no renoprotective action, suggesting that the effects on LDL-subtype distribution do not directly lead to renoprotection.