At UCSF, we have used
sirolimus in several immunosuppression regimens and protocols, and this article will summarize our experience in four areas. The purpose of the first study was to assess the efficacy of a
sirolimus-based,
calcineurin inhibitor-free regimen for the first 3 months after
transplantation. Patients were treated with a
calcineurin inhibitor-free regimen that consisted of
daclizumab,
sirolimus,
mycophenolate mofetil (MMF), and conventional
corticosteroids. Of nine patients, one (case #7) had an acute rejection episode (type IA) at 2 months after
transplantation, which was fully reversed with
corticosteroids. The second study was a prospective trial of
calcineurin inhibitor-free regimen in patients with severe
delayed graft function (DGF) (requiring dialysis). The immunosuppression regimen consisted of
daclizumab,
sirolimus, MMF, and
corticosteroids. This immunosuppressive regimen was effective in patients with DGF; however, it was effective only in non-African American (non-AA) patients (AA had a significantly higher acute rejection rate at 1 year than non-AA, 63% vs 23%, P =.025). In some patients
sirolimus was associated with a prolonged recovery from DGF. The addition of
sirolimus to
immunosuppressive agents provide the opportunity for safe
steroid withdrawal (at day 5). We participated in a
sirolimus-based, multicenter open-label trial of very early
corticosteroid withdrawal. Primary renal transplant patients were enrolled in an immunosuppression regimen that consisted of
basiliximab,
sirolimus (target levels 8 to 15 ng/mL, 0 to 5 months, and 6 to 12 ng/mL, 6 to 12 months) and
tacrolimus in a dose of 0.05 mg/kg BID (target levels 6 to 9 ng/mL). Two of 14 enrolled patients had an episode of acute rejection before
steroids were withdrawn. No acute rejection episodes have occurred after
steroids were withdrawn (6-month follow-up). The regimen of
sirolimus and
tacrolimus was well tolerated.
Wound complications were not noted. Another important use of
sirolimus has been its incorporation in the immunosuppressive regimens in kidney-
pancreas transplantation. Our current protocol consists of
thymoglobulin induction, combined with MMF,
sirolimus, and low-dose
tacrolimus, for maintenance
therapy.
Steroids are only utilized during the first 5 to 6 days following the transplant. This
steroid-free maintenance regimen has been used in the last 30 enteric-drained, simultaneous pancreas-kidney transplants. Using this immunosuppressive approach, rejection rates are less than 10% for either the kidney or the pancreas.