A CALCINEURIN ANTAGONIST-FREE INDUCTION STRATEGY FOR IMMUNOSUPPRESSION IN CADAVERIC KIDNEY TRANSPLANT RECIPIENTS AT RISK FOR DELAYED GRAFT FUNCTION1

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Abstract
Avoidance of calcineurin antagonists for a prolonged period de novo after cadaver donor renal transplantation may facilitate recovery from delayed graft function. The present study examined the benefit of prolonging the calcineurin antagonist-free interval by administering sirolimus (SRL) in combination with chimeric (c-) anti-interleukin-2 receptor (IL-2R) monoclonal antibodies (mAb). 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 function were treated with either SRL/c-IL-2R mAb/prednisone (Pred) with inception of cyclosporine (CsA) once the serum creatinine value was ≤2.5 mg/dl (n=43; group 1) or anti-lymphocyte preparations/Pred/delayed CsA for 7 to 14 days (n=18; group 3). A third cohort displayed immediate function and was treated de novo with CsA/c-IL-2R mAb/Pred (n=21; group 2). 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 among African-American or retransplant recipients, and a separate cluster of six of seven occurred among patients who displayed SRL trough concentrations ≤9 ng/ml. Furthermore, additional antilymphocyte antibody treatment was required to reverse either steroid-resistant or Banff grades 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 survival rates, as well as mean serum creatinine values, were similar at 12 months 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. This pilot study suggests that a SRL/c-IL-2R mAb/Pred induction regimen provides excellent acute rejection prophylaxis.