Effect of calcineurin inhibitors on low-density lipoprotein oxidation.
BACKGROUND
Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients.


OBJECTIVE
The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients.


METHODS
We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels.


RESULTS
The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s]).


CONCLUSIONS
In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment.
Cofan
F
F
Renal Transplant Unit, Hospital Clínic, Barcelona, Spain. fcofan@clinic.ub.es
Cofan
M
M
Campos
B
B
Guerra
R
R
Campistol
J-M
JM
Oppenheimer
F
F
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019703:Calcineurin / Q000009:adverse effects*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D008077:Lipoproteins, LDL; D016572:Cyclosporine; D002784:Cholesterol; D003404:Creatinine; D019703:Calcineurin; D016559:Tacrolimus