Long-term kidney allograft function and survival in prednisone-free regimens: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus

Abstract

Background and objectives: The optimal maintenance immunosuppressive regimen to improve long-term renal allograft function and graft survival is yet to be determined.

Design, setting, participants, & measurements: This observational study prospectively compared tacrolimus/sirolimus with tacrolimus/mycophenolate mofetil in renal transplant recipients using a prednisone-free regimen with over 8.5 years of follow-up. Patients received methylprednisonlone and anti-IL2 receptor antagonist (Basiliximab) induction and were blindly randomized to either the tacrolimus/mycophenolate mofetil (n=45) or tacrolimus/sirolimus (n=37) groups. Outcome measures included patient and renal allograft survival, incidence of acute rejection, and estimated GFR.

Results: The tacrolimus/mycophenolate mofetil group compared with the tacrolimus/sirolimus group had overall better renal allograft survival (91% versus 70%, P=0.02); 13 patients (35.1%) in the tacrolimus/sirolimus group and 8 patients (17.8%) in the tacrolimus/mycophenolate mofetil group experienced biopsy-proven acute cellular rejection (P=0.07). By 3 months post-transplant, estimated GFR was significantly lower in the tacrolimus/sirolimus group compared with the tacrolimus/mycophenolate mofetil group (47.7 versus 59.6 ml/min per 1.73 m(2), P=0.0002), and this trend persisted throughout the follow-up period. Also, the slope of decline in the tacrolimus/sirolimus group was significantly steeper than in the tacrolimus/mycophenolate mofetil group.

Conclusions: This study shows that, in a prednisone-free immunosuppressive regimen, long-term renal graft survival and function are significantly worse in the tacrolimus/sirolimus group than the tacrolimus/mycophenolate mofetil group. The synergistic nephrotoxic effect and higher acute rejection rates in the tacrolimus/sirolimus compared with the tacrolimus/mycophenolate mofetil group adversely affect graft survival.

Figure 1.

Consolidated Standards of Reporting Trials flow diagram.

Figure 2.

Cumulative patient survival, renal allograft survival, and rejection-free survival in tacrolimus/mycophenolate mofetil (Tac/MMF) and Tac/sirolimus (Tac/SRL) groups. Kaplan–Meier patient survival curves. Log-rank test (A, P=0.05; B, P=0.01; C, P=0.08). *Numbers at risk in each group.

Figure 3.

Estimated GFR and Tac trough levels according to treatment groups; Tac/MMF versus Tac/SRL. (A) The GFR slope was significantly steeper in the Tac/SRL group (P=0.02). (B) There was no difference in Tac level over time between Tac/MMF and Tac/SRL groups (P>0.05).