Fluvastatin reduces atherogenic lipids without any effect on native endothelial function early after kidney transplantation.
BACKGROUND
Cardiovascular risk is greatly increased in renal transplant recipients. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy may reduce cardiovascular risk by improving both dyslipidemia and endothelial function. We therefore performed this study to assess the effect of fluvastatin on endothelial function in renal transplant recipients.


METHODS
This randomized, placebo-controlled, double-blind designed study investigated the effect of fluvastatin on endothelial function. Thirty-seven recipients received fluvastatin 40 mg/d and 35 received placebo during the first 12 wk following transplantation. All patients initially received cyclosporin A, prednisolone and azathioprine. At the end of treatment, endothelial function was assessed in the forearm skin microvasculature by laser Doppler flowmetry following acetylcholine stimulation. Samples were taken for measurements of serum lipids and vasoactive markers.


RESULTS
There were no differences in endothelial function between fluvastatin recipients and controls, AUCACh was 656 +/- 479 and 627 +/- 518 AU min, respectively (fluv vs. control, p > 0.65). In the placebo limb, total cholesterol and LDL cholesterol increased 22 +/- 12% and 22 +/- 18%, respectively in the first 12 wk following transplantation. The respective values were 18 +/- 13% (p = 0.010) and 34 +/- 19% (p = 0.0013) lower at 12 wk in the fluvastatin treated patients. Plasma ET-1, BigET-1 and urinary excretion of cGMP were not significantly different between treatment groups (p > 0.55).


CONCLUSIONS
Although fluvastatin 40 mg/d significantly lowers cholesterol it does not affect endothelial function the first 3 months after renal transplantation. The lack of effect on endothelial function is consistent with a lack of effect on vasoactive substances.
Asberg
Anders
A
Laboratory for Renal Physiology, Section of Nephrology, Medical Department, The National Hospital, Oslo, Norway. anderas@klinmed.uio.no
Holdaas
Hallvard
H
Jardine
Alan G
AG
Edvardsen
Cecilie
C
Hartmann
Anders
A
D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000098:blood supply
D008078:Cholesterol, LDL; D019332:Endothelin-1; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D008055:Lipids; D000077340:Fluvastatin; D002784:Cholesterol