Sirolimus rescue therapy for refractory rejection in renal transplantation

Background. Acute renal allograft rejection episodes refractory to antilymp hocyte preparations almost inevitably progress to transplantation loss. To reverse ongoing rejection processes, we administered sirolimus (RAPA) after failure of conventional immunosuppressive regimens including full courses of antilymphocyte sera. Methods. All 36 renal transplantation recipients reported herein displayed either Grade IIB or Grade III biopsy-proven (Banff 1993 criteria) ongoing r ejection episodes despite prior treatment with pulse and/or oral recycling of steroids and at least one 14- to 21-day course of murine (OKT3) or equin e (ATGAM) antilymphocyte treatment. We compared the actual 12-month outcome s of two demographically similar cohorts of patients treated for refractory rejection with RAPA (Group I; n=24) or mycophenolate mofetil (MMF; Group I I; n=12) added to a baseline regimen of cyclosporine (CsA)/prednisone (Pred ). Results. Rescue therapy reversed the renal dysfunction in 96% of patients i n the RAPA group versus 67% in the MMF group (P=0.03) despite the fact that a greater fraction of patients in the RAPA (17 of 24) than the MMF group ( 6 of 12) had experienced two or more episodes of acute rejection before stu dy entry and the fact that the recurrent bouts of acute rejection occurred within the first 6 months posttransplant in 94% of patients in the RAPA gro up compared with 50% (P=0.005) in the MMF group. Among the patients who wer e reversed successfully, the rates of rebound acute rejection were similar (4% vs. 8%). The mean serum creatinine values were slightly, although not s ignificantly, lower among RAPA than MMF patients at 1, 3, 6, and 12 months: namely, 2.6 vs. 2.8, 2.8 vs. 3.2, 3.0 vs. 3,3, and 2.8 vs. 3.2 mg/dL, resp ectively. The 1-year patient and graft survival rates were similar: namely, 88% vs. 92% and 83% vs. 67% for the RAPA versus MMF groups. Conclusion. RAPA is a potent immunosuppressive agent for the treatment of r efractory renal allograft rejection.