Effect of gemfibrozil on lipoprotein abnormalities in chronic renal insufficiency: a controlled study in human chronic renal disease.
BACKGROUND
Renal dyslipoproteinemia is characterized by the accumulation of intact and partially metabolized triglyceride-rich lipoproteins. Reduced lipolytic enzyme activities may be one of the major pathophysiological mechanisms contributing to a retarded catabolism of these lipoproteins in patients with renal insufficiency.


OBJECTIVE
To evaluate the effect of gemfibrozil treatment on renal dyslipoproteinemia.


METHODS
A randomized, controlled open study with 2 parallel groups.


METHODS
Plasma concentrations of lipids, apolipoproteins and lipoprotein particles.


METHODS
Fifty-seven non-nephrotic, non-diabetic patients with moderately advanced renal insufficiency were randomized to either treatment with gemfibrozil at dosages from 300 to 900 mg/day (n = 28) or dietary counseling (n = 29). The intervention period was 12 months. Plasma concentrations of lipids, apolipoproteins and apoA- and apoB-containing lipoprotein particles were determined at the entry and after 6 and 12 months of treatment.


RESULTS
No serious adverse effects occurred during the study. Six patients experienced mild gastrointestinal symptoms and prematurely withdrew from the drug treatment. In the group treated with gemfibrozil the plasma concentrations of triglycerides, total cholesterol, very low density lipoprotein (VLDL) and low density (LDL) cholesterol decreased significantly by 47, 13, 43 and 14%, respectively, in comparison to baseline. High density lipoprotein (HDL) cholesterol increased significantly by 18%. ApoB, apoC-III, apoC-III in heparin-manganese precipitate (reflecting apoC-III in VLDL and LDL) and apoE decreased significantly by 21, 18, 26 and 49%, respectively. Furthermore, gemfibrozil treatment resulted in the reduction of plasma concentrations of complex (LP-Bc) and simple (LP-B) apoB-containing lipoprotein particles by 22 and 7%, respectively. However, these changes were not statistically significant. There was a slight, insignificant increase in the levels of LP-A-I:A-II particles and no change in the levels of LP-A-I particles. In contrast to the effect of the pharmacological intervention, the dietary counseling only resulted in minor changes in the plasma lipid and apolipoprotein profiles. The only significant changes were a 10% increase in HDL cholesterol and a 35% decrease in apoE.


CONCLUSIONS
Gemfibrozil treatment significantly reduces both plasma lipids and apoB, apoC-III and apoE concentrations in patients with moderately advanced renal insufficiency. The results of this study indicate that gemfibrozil enhances the clearance of apoB-containing triglyceride-rich lipoproteins.
Samuelsson
O
O
Department of Nephrology, University of Göteborg, Sweden.
Attman
P O
PO
Knight-Gibson
C
C
Kron
B
B
Larsson
R
R
Mulec
H
H
Weiss
L
L
Alaupovic
P
P
D001053:Apolipoproteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000178:diet therapy; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged
D001053:Apolipoproteins; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D002784:Cholesterol; D015248:Gemfibrozil