The impact of FTY720 (fingolimod) on vasodilatory function and arterial elasticity in renal transplant patients.
BACKGROUND
FTY720 has recently demonstrated a similar efficacy in prevention of acute graft rejection compared with mycophenolate mofetil (MMF) in a large phase III trial of de novo renal transplant recipients. Creatinine clearance, however, was significantly lower in FTY720-treated patients. In the present study, we examined the impact of FTY720 on vascular function in a subgroup of patients of this trial.


METHODS
Eighteen patients (12 FTY720, 6 MMF) agreed to be enrolled for an analysis of vascular function. Vascular measurements were performed 1.5 years post-transplant and were repeated 3 months after conversion of the patients from FTY720 to MMF. Arterial stiffness was assessed as augmentation index (AI(75)); endothelium-dependent and -independent vasodilation were measured sonographically as flow-mediated dilation (FMD) and as vasodilation after application of glyceroltrinitrate (GTN).


RESULTS
Conversion from 2.5 mg FTY720 to MMF led to a significant improvement of FMD (5.40 +/- 1.84 vs 7.77 +/- 3.36%, P 0.02). AI(75) and GTN tended to be higher after conversion without reaching significance (83 +/- 20.43 vs 78.69 +/- 15.39%, P 0.06; 13.76 +/- 4.52 vs 17.39 +/- 3.76%, P 0.07). In the MMF group, AI(75), FMD and GTN did not significantly change during the observation period.


CONCLUSIONS
The present study constitutes the first analysis of the impact of FTY720 on vascular function in humans and reveals an improvement of arterial vasodilatory function after discontinuation of FTY720 in de novo renal transplant recipients on cyclosporine.
Westhoff
Timm H
TH
Centrum 10 - Nephrology, Charité - Campus Benjamin Franklin, 12200 Berlin, Germany. timm.westhoff@charite.de
Schmidt
Sven
S
Glander
Petra
P
Liefeld
Lutz
L
Martini
Sebastian
S
Offermann
Gerd
G
Neumayer
Hans H
HH
Zidek
Walter
W
van der Giet
Markus
M
Budde
Klemens
K
D000328:Adult; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008875:Middle Aged; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects*
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine