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


RESULTS
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 >or=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.
Yasuda
Gen
G
Division of Nephrology, Center Hospital, School of Medicine, Yokohama City University, Yokohama, Japan. y911429@urahp.yokohama-cu.ac.jp
Ando
Daisaku
D
Hirawa
Nobuhito
N
Umemura
Satoshi
S
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D018592:Cross-Over Studies; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D007674:Kidney Diseases / Q000150:complications* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011341:Probucol / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D000069059:Atorvastatin; D011341:Probucol