Randomized trial of 3 maintenance regimens (tac/srl vs. tac/mmf vs. csa/srl) with low dose corticosteroids in primary kidney transplantation: 18 year results.

A randomized trial of 150 primary kidney transplant recipients, initiated in May,2000, compared tacrolimus(TAC)/sirolimus(SRL) vs. TAC/mycophenolate mofetil(MMF) vs. cyclosporine microemulsion(CSA)/SRL(N=50/group). All patients received daclizumab induction and maintenance corticosteroids. With current median follow-up of 18yr post-transplant, biopsy-proven acute rejection(BPAR) occurred less often in TAC/MMF, 26%(13/50), vs. the TAC/SRL (36%(18/50)) and CSA/SRL (34%(17/50)) arms combined(P=.23), with statistical significance favoring TAC/MMF(P=.05) after controlling for the multivariable(Cox model) effects of recipient age, recipient race/ethnicity, and donor age. First BPAR rate was clearly more favorable for TAC/MMF after stratifying patients by having 0-1(N=72) vs. 2-3(N=78) unfavorable baseline characteristics(recipient age<50yr, African-American or Hispanic recipient, and donor age≥50yr)(P=.02). Mean estimated glomerular filtration rate(eGFR), using the CKD-EPI formula, was consistently higher for TAC/MMF, particularly after controlling for the multivariable effect of donor age, throughout the first 96mo post-transplant(P≤.008). These differences translated into an observed more favorable graft failure due-to-immunologic cause(CAI/TG) rate for TAC/MMF(P=.06), although no significant differences in overall death-uncensored graft loss were observed. Previously reported significantly higher study drug discontinuation and requirement-for-anti-lipid therapy rates in the SRL-assigned arms were maintained over time. Overall, these results at 18yr post-transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long-term maintenance immunosuppression in kidney transplantation.