Mycophenolic acid concentrations in long-term heart transplant patients: relationship with calcineurin antagonists and acute rejection.
BACKGROUND
When used in conjunction with steroids and cyclosporin, mycophenolate mofetil (MMF) has been shown to significantly reduce mortality and incidence of rejection in the first year after heart transplantation. It also appears that in this early post-transplantation period, the monitoring of immunosuppressive therapies may be warranted. The current study was undertaken to determine if such monitoring is still useful more than 1 yr after heart transplantation.


METHODS
Twenty-six patients who had survived the first year after orthotopic heart transplantation and had been on MMF therapy for more than 3 months were prospectively followed. At the time of their routine endomyocardial biopsy blood samples were taken to monitor immunosuppressive therapy. Most patients had two samples taken, on average 109 d apart.


RESULTS
There were 22 episodes of asymptomatic rejection documented on a total of 48 biopsies. Of these, only two were of ISHLT (International Society for Heart and Lung Transplantation) grade 3A the remainder being of ISHLT grades 1 or 2. There was no relation between immunosuppressive regimen (tacrolimus and MMF or cyclosporin and MMF) and rejection. There was no relation between monitored immunosuppressive levels and rejection. Patients with the combination of MMF and tacrolimus had significantly higher plasma mycophenolic acid levels despite significantly lower daily MMF dose.


CONCLUSIONS
There does not appear to be a benefit in continued monitoring of plasma mycophenolic acid levels beyond the first year of heart transplantation. There were significant differences in plasma mycophenolic acid levels depending on the type of calcineurin inhibitor concomitantly used.
Cantin
Bernard
B
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Giannetti
Nadia
N
Parekh
Hemal
H
Panchal
Shyam N
SN
Kwok
Bernard W-K
BW
Najem
Ruhina
R
Woodman
Katina
K
Hunt
Sharon A
SA
Valantine
Hannah A
HA
D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D016027:Heart Transplantation; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D011184:Postoperative Period; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D016572:Cyclosporine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D016559:Tacrolimus