Sirolimus rescue therapy for refractory rejection in renal transplantation.
BACKGROUND
Acute renal allograft rejection episodes refractory to antilymphocyte 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 rejection 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 equine (ATGAM) antilymphocyte treatment. We compared the actual 12-month outcomes of two demographically similar cohorts of patients treated for refractory rejection with RAPA (Group I; n=24) or mycophenolate mofetil (MMF; Group II; n=12) added to a baseline regimen of cyclosporine (CsA)/prednisone (Pred).


RESULTS
Rescue therapy reversed the renal dysfunction in 96% of patients in 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 study 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 group compared with 50% (P=0.005) in the MMF group. Among the patients who were reversed successfully, the rates of rebound acute rejection were similar (4% vs. 8%). The mean serum creatinine values were slightly, although not significantly, 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, respectively. The 1-year patient and graft survival rates were similar: namely, 88% vs. 92% and 83% vs. 67% for the RAPA versus MMF groups.


CONCLUSIONS
RAPA is a potent immunosuppressive agent for the treatment of refractory renal allograft rejection.
Hong
J C
JC
Division of Immunology and Organ Transplantation, The University of Texas Medical School at Houston, 6431 Fannin, Suite 6.240, Houston, TX 77030, USA.
Kahan
B D
BD
D000328:Adult; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D009994:Osmolar Concentration; D011241:Prednisone / Q000627:therapeutic use; D016879:Salvage Therapy; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D020123:Sirolimus