A calcineurin antagonist-free induction strategy for immunosuppression in cadaveric kidney transplant recipients at risk for delayed graft function

Background. Avoidance of calcineurin antagonists for a prolonged period de novo after cadaver donor rend transplantation may facilitate recovery from delayed graft function. The present study examined the benefit of prolongin g the calcineurin antagonist-free interval by administering sirolimus (SRL) in combination with chimeric (c-) anti-interleukin-2 receptor (IL-2R) mono clonal antibodies (mAb). Methods. Three contemporaneous but nonrandomized cohorts were compared for acute rejection episodes, patient and graft survival rates, renal function, and adverse reaction profiles for 12 months. Patients with delayed graft f unction were treated with either SRL/c-IL-2R mAb/prednisone (Pred) with inc eption of cyclosporine (CsA) once the serum creatinine value was less than or equal to2.5 mg/dl (n=43; group I) or anti-lymphocyte preparations/Pred/d elayed CsA for 7 to 14 days (n=18; group 3). A third cohort displayed immed iate function and was treated de novo with CsA/c-IL-2R mAb/Pred (n=21; grou p 2). Results. The incidence of acute rejection episodes was significantly lower among group 1 (16%) compared with groups 2 (52%, P=0.004) or 3 (39%, P=0.05 ). Among the seven rejection episodes in group 1, six of seven occurred amo ng African-American or refransplant recipients, and a separate cluster of s ix of seven occurred among patients who displayed SRL trough concentrations less than or equal to9 ng/ml, Furthermore, additional antilymphocyte antib ody treatment was required to reverse either steroid-resistant or Banff gra des II or III acute rejection episodes among 14%, 55% (P = 0.08), and 71% ( P = 0.03) of patients in each group, respectively. Patient and graft surviv al rates, as well as mean serum creatinine values, were similar at 12 month s among the three groups. However, group 1 patients displayed higher serum cholesterol and triglyceride values, as well as lower hemoglobin, platelet, and leukocyte values compared with the other two groups. Conclusion. This pilot study suggests that a SRL/c-IL-2R mAb/Pred induction regimen provides excellent acute rejection prophylaxis.