Tacrolimus-induced elevation in plasma triglyceride concentrations after administration to renal transplant patients is partially due to a decrease in lipoprotein lipase activity and plasma concentrations.
BACKGROUND
Hyperlipidemia is a frequent and persistent complication in solid organ transplant recipients, leading to the high occurrence of cardiovascular disease in this patient population. Lipid abnormalities including increased total cholesterol, triglycerides (TG), and low-density lipoprotein-cholesterol have been reported frequently in transplantation patients and a variety of immunosuppressive therapies seem to be one of the main factors that influence posttransplant lipidemic profiles. For many years, tacrolimus (TAC) has been used as an immunosuppressive drug in transplantation. The aim of our investigation was to determine the effect of TAC administration on the plasma lipid profile and some key regulatory proteins of plasma lipid metabolism including cholesterol ester transfer protein, hepatic lipase and lipoprotein lipase (LPL) within renal transplant patients.


METHODS
Twenty-five renal transplant patients were recruited and received TAC therapy, of which nine of these patients were treated with statin therapy for dyslipidemia. The effects of TAC on plasma total cholesterol, TG, HDL-C, low-density lipoprotein-cholesterol, cholesterol ester transfer protein, hepatic lipase and LPL concentration and activity were determined from patients plasma samples collected before the transplant surgery (baseline), and weekly for four consecutive weeks after surgery and TAC administration.


RESULTS
We observed that TAC significantly increases plasma TG concentrations and reduces LPL plasma concentration and activity in renal transplant patients, independent of any lipid lowering drug treatment patients received.


CONCLUSIONS
Taken together, these findings suggest that the reduction in LPL activity, partly due to the decrease of plasma LPL concentration after TAC administration may be an explanation for hypertriglyceridemia observed in patients administered TAC.
Tory
Rita
R
Faculty of Medicine, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Sachs-Barrable
Kristina
K
Goshko
Caylee-Britt
CB
Hill
John S
JS
Wasan
Kishor M
KM
D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D015536:Down-Regulation; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015228:Hypertriglyceridemia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood; D016030:Kidney Transplantation; D008049:Lipase / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects* / Q000097:blood; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; C504173:LIPC protein, human; D014280:Triglycerides; D002784:Cholesterol; D008049:Lipase; D008071:Lipoprotein Lipase; D016559:Tacrolimus