Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

Abstract

Calcineurin inhibitor-associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients.

Methods: This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m(2) or greater improvement in estimated glomerular filtration rate from randomization to month 24.

Results: The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m(2) or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012).

Conclusions: Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus.

FIGURE 1

Disposition of the study population. *Received ≥1 dose of assigned therapy. ^†Remained on assigned therapy through 24 months after transplantation for the primary end point. d/c, discontinued; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis.

FIGURE 2

Percentage of patients with at least a 5-mL/min per 1.73 m² improvement in renal function at 12 and 24 months after transplantation (on-therapy population).

FIGURE 3

Change from baseline in eGFR by abbreviated MDRD (on-therapy population). Change from baseline was summarized based on patients with valid values available for both baseline and the study visit. MDRD, Modification of Diet in Renal Disease.

FIGURE 4

Incidence of posttransplantation diabetes mellitus over 24 months after randomization. The at-risk population for posttransplantation diabetes mellitus included only those patients who were not already categorized as having diabetes at or before randomization, per protocol definition.