Prospective randomized trial of maintenance immunosuppression with rapid discontinuation of prednisone in adult kidney transplantation

Rapid discontinuation of prednisone (RDP) has minimized steroid-related complications following kidney transplant (KT). This trial compares long-term (10-year) outcomes with three different maintenance immunosuppressive protocols following RDP in adult KT. Recipients (n = 440; 73% living donor) from March 2001 to April 2006 were randomized into one of three arms: cyclosporine (CSA) and mycophenolate mofetil (MMF) (CSA/MMF, n = 151); high-level tacrolimus (TAC, 8-12 μg/L) and low-level sirolimus (SIR, 3-7 μg/L) (TAC ^H/SIR^L, n = 149) or low-level TAC (3-7 μg/L) and high-level SIR (8-12 μg/L) (TAC^L/SIR^H, n = 140). Median follow-up was ∼7 years. There were no differences between arms in 10-year actuarial patient, graft and death-censored graft survival or in allograft function. There were no differences in the 10-year actuarial rates of biopsy-proven acute rejection (30%, 26% and 20% in CSA/MMF, TAC ^H/SIR^L and TAC^L/SIR^H) and chronic rejection (38%, 35% and 31% in CSA/MMF, TAC^H/SIR^L and TAC^L/SIR^H). Rates of new-onset diabetes mellitus were higher with TAC^H/SIR^L (p = 0.04), and rates of anemia were higher with TAC^H/SIR^L and TAC^L/SIR^H (p = 0.04). No differences were found in the overall rates of 16 other post-KT complications. These data indicate that RDP-based protocol yield acceptable 10-year outcomes, but side effects differ based on the maintenance regimen used and should be considered when optimizing immunosuppression following RDP.