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

Abstract 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 18 years 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 <50 years, African American or Hispanic recipient, and donor age ≥50 years) ( 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 96 months post‐transplant ( p ≤ .008). These differences were 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 antilipid therapy rates in the SRL‐assigned arms were maintained over time. Overall, these results at 18 years post‐transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long‐term maintenance immunosuppression in kidney transplantation.