A calcineurin inhibitor-sparing regimen with sirolimus, mycophenolate mofetil, and anti-CD25 mAb provides effective immunosuppression in kidney transplant recipients with delayed or impaired graft function

Abstract

Delayed graft function (DGF) after renal transplantation is a significant risk factor for early acute rejection and graft loss. Sirolimus (SRL) can be administered in the setting of DGF without exacerbating the impaired renal function after transplantation. We examined a calcineurin-sparing regimen using SRL during the early post-operative period in renal transplant patients with delayed or impaired graft function. A retrospective review of 14 consecutive kidney transplant recipients with delayed or impaired graft function who received SRL was performed. The immunosuppressive regimen consisted of daclizumab induction (2 mg/kg), SRL (5-15 mg load followed by 2 5 mg daily maintenance therapy), corticosteroids, and mycophenolate mofetil (MMF, 1.5-3 g/d). Patients were monitored for allograft function, acute rejection, graft survival, thrombocytopenia, and leukopenia. Serum levels of SRL were determined by high-performance liquid chromatography performed at an independent commercial laboratory. Donors were cadaveric in 13 cases and living related in one. The duration of follow-up was 0.5-5.2 months. Nine patients required hemodialysis after transplantation. The mean time to initiation of calcineurin inhibitors was 21 +/- 13 d. Average serum creatinine levels at the initiation of SRL and at 1 month after transplantation were 8.4 +/- 2.7 and 2.1 +/- 1.2 mg/dL, respectively. There were 2 patients (14%) who experienced acute rejection within the first month after transplantation -1 with type I (steroid therapy) and 1 with type II (anti-thymocyte therapy). Serum levels of SRL were initially undetectable in the 2 patients with acute rejection. No grafts were lost during the period of follow-up. Three patients developed thrombocytopenia (platelets < 100 x 10(9)) and no patients developed leukopenia. The combination of SRL with anti-CD25 mAb, MMF, and corticosteroids appears to provide effective non-nephrotoxic immunosuppression for kidney transplantation without the need for a lymphocyte-depleting regimen. However, it is important to monitor serum SRL levels to determine the optimal dosing regimen. Furthermore, long-term follow-up of these patients will be helpful to determine whether improved immunosuppression can be achieved with a fully calcineurin-sparing regimen using SRL.