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
Gj. Chang et al., 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, CLIN TRANSP, 14(6), 2000, pp. 550-554
Delayed graft function (DGF) after renal transplantation is a significant r
isk 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 patien
ts 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 immu
nosuppressive regimen consisted of daclizumab induction (2 mg/kg), SRL (5-1
5 mg load followed by 2-5 mg daily maintenance therapy), corticosteroids, a
nd mycophenolate mofetil (MMF, 1.5-3 g/d). Patients were monitored for allo
graft function, acute rejection, graft survival, thrombocytopenia, and leuk
openia. Serum levels of SRL were determined by high-performance liquid chro
matography performed at an independent commercial laboratory. Donors were c
adaveric in 13 cases and living related in one. The duration of follow-up w
as 0.5-5.2 months. Nine patients required hemodialysis after transplantatio
n. The mean time to initiation of calcineurin inhibitors was 21 +/- 13 d. A
verage serum creatinine levels at the initiation of SRL and at 1 month afte
r transplantation were 8.4 +/- 2.7 and 2.1 +/- 1.2 mg/dL, respectively. The
re were 2 patients (14%) who experienced acute rejection within the first m
onth after transplantation - 1 with type I(steroid therapy) and 1 with type
II(anti-thymocyte therapy). Serum levels of SRL were initially undetectabl
e in the 2 patients with acute rejection. No grafts were lost during the pe
riod of followup. Three patients developed thrombocytopenia (platelets < 10
0 x 10(9)) and no patients developed leukopenia. The combination of SRL wit
h anti-CD25 mAb, MMF, and corticosteroids appears to provide effective non-
nephrotoxic immunosuppression for kidney transplantation without the need f
or a lymphocyte-depleting regimen. However, it is important to monitor seru
m SRL levels to determine the optimal dosing regimen. Furthermore, long-ter
m follow-up of these patients will be helpful to determine whether improved
immunosuppression can be achieved with a fully calcineurin-sparing regimen
using SRL.