C. Johnson et al., Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mychophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation, TRANSPLANT, 69(5), 2000, pp. 834-841
Background. Our clinical trial was designed to investigate the optimal comb
ination of immunosuppressants for renal transplantation.
Methods. A randomized three-arm, parallel group, open label, prospective st
udy was performed at 15 North American centers to compare three immunosuppr
essive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neora
l) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were
first cadaveric kidney transplants receiving the same maintenance corticos
teroid regimen. Only patients with delayed graft function (32%) received an
tilymphocyte induction. A total of 223 patients were randomized, transplant
ed, and followed for 1 year.
Results. There were no significant differences in baseline demography betwe
en the three treatment groups. At 1 year the results are as follows: acute
rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (c
onfidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence int
erval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant reje
ction requiring antilymphocyte therapy was 12% in the tacrolimus + AZA grou
p, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF grou
p. There were no significant differences in overall patient or graft surviv
al. Tacrolimus-treated patients had a lower incidence of hyperlipidemia thr
ough 6 months posttransplant. The incidence of posttransplant diabetes mell
itus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyc
losporine + MMF and 7% in the tacrolimus + MMF groups.
Conclusions, All regimens yielded similar acute rejection rates and graft s
urvival, but the tacrolimus + MMF regimen was associated with the lowest ra
te of steroid resistant rejection requiring antilymphocyte therapy.