Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years.
METHODS
Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), or cyclosporine (Neoral; CsA) + MMF. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function (DGF). Patients were followed-up for 3 years.


RESULTS
The results at 3 years corroborate and extend the findings of the 2-year results. Patients with DGF treated with TAC+MMF experienced an increase in 3-year allograft survival compared with patients receiving CsA+MMF (84.1% vs. 49.9%, P=0.02). Patients randomized to either treatment arm containing TAC exhibited numerically superior kidney function when compared with CsA. During the 3 years, new-onset insulin dependence occurred in 6, 3, and 11 patients in the TAC+MMF, CsA+MMF, and TAC+AZA treatment arms, respectively. Furthermore, patients randomized to TAC+MMF received significantly lower doses of MMF as compared with those who received CsA+MMF.


CONCLUSIONS
All three immunosuppressive regimens provided excellent safety and efficacy. However, the best results overall were achieved with TAC+MMF. The combination may provide particular benefit to kidney allograft recipients with DGF. In patients who experienced DGF, graft survival was better at 3 years in those patients receiving TAC in combination with either MMF or AZA as compared with the patients receiving CsA with MMF.
Gonwa
Thomas
T
Mayo Clinic Transplant Center, 4205 Belfort Blvd., Suite 1100, Jacksonville, FL, 32216, USA.
Johnson
Christopher
C
Ahsan
Nasimul
N
Alfrey
Edward J
EJ
Halloran
Philip
P
Stegall
Mark
M
Hardy
Mark
M
Metzger
Robert
R
Shield
Charles
C
Rocher
Leslie
L
Scandling
John
J
Sorensen
John
J
Mulloy
Laura
L
Light
Jimmy
J
Corwin
Claudia
C
Danovitch
Gabriel
G
Wachs
Michael
M
VanVeldhuisen
Paul
P
Leonhardt
Maryanne
M
Fitzsimmons
William E
WE
D000208:Acute Disease; D001379:Azathioprine / Q000627:therapeutic use*; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005431:Florida; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology*; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality / Q000502:physiology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000453:epidemiology; D011336:Probability; D044469:Racial Groups; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors
D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D001379:Azathioprine; D016559:Tacrolimus