Long-term efficacy and safety of a calcineurin inhibitor-free regimen in live-donor renal transplant recipients

Abstract

Calcineurin inhibitor (CNI) nephrotoxicity is a major concern after renal transplantation. To investigate the safety and efficacy of a CNI-free immunosuppressive regimen, 132 live-donor renal transplant recipients were included in a prospective, randomized controlled trial. All patients received induction therapy with basiliximab and steroids. The patients were randomized to a maintenance immunosuppression regimen that included steroids, sirolimus, and either low-dose tacrolimus or mycophenolate mofetil (MMF). Over a mean follow-up period of approximately 5 yr, patient and graft survival did not significantly differ between the two maintenance regimens. Patient survival was 93.8% and 98.5% in the tacrolimus/sirolimus and MMF/sirolimus groups, respectively, and graft survival was 83% and 88%, respectively. However, the MMF/sirolimus group had significantly better renal function, calculated by Cockcroft-Gault, from the second year post-transplant until the last follow-up. In addition, this group was less likely to require a change in their primary immunosuppression regimen than the tacrolimus/sirolimus group (20.8% versus 53.8%, P = 0.001). The safety profile was similar between groups. In summary, after long-term follow-up, a CNI-free maintenance regimen consisting of sirolimus, MMF, and steroids was both safe and efficacious among low to moderate immunologic risk renal transplant recipients.

Figure 1.

Patient survival relative to the primary immunosuppression in groups A (Tac) and B (MMF).

Figure 2.

Graft survival relative to the primary immunosuppression in groups A (Tac) and B (MMF).

Figure 3.

Sirolimus trough levels (ng/ml) in both groups.

Figure 4.

Graft function based on intention-to-treat analysis (all cases are included) as estimated by calculated GFR (ml/min).

Figure 5.

Graft function based on maintenance of primary immunosuppressive regimen (all cases with secondary immunosuppression are excluded) as estimated by calculated GFR (ml/min).