CASE REPORT-SIROLIMUS RESCUE THERAPY FOR REFRACTORY RENAL ALLOGRAFT REJECTION1

Abstract

Sirolimus not only displays prophylactic activity, it also reverses acute rejection in rats with ongoing renal allograft rejection. The present case of a human renal allograft recipient documents the utility of dual-drug cyclosporine (CsA)/sirolimus therapy for a patient experiencing ongoing acute rejection and renal dysfunction that had not abated after treatment with corticosteroids equine antilymphocyte globulin (ATGAM), or the mouse anti-human CD3 monoclonal antibody OKT3. The patient described herein underwent induction therapy with 7 days of OKT3, and anti-rejection treatment with 14 days of ATGAM followed by 6 days of OKT3 therapy for biopsy-proved rejection episodes that rendered the patient dependent on dialysis treatments, oliguric with a urine output less than 650 ml per day, and uremic with a serum creatinine (sCr) value above 7 mg/dl. When OKT3 therapy was ceased because of the presence of human anti-mouse antibodies, sirolimus was added to the CsA/steroid regimen to treat the ongoing rejection and to reverse the markedly decreased renal perfusion, as revealed by a 99mTc-DTPA scan. Within 6 weeks the patient's sCr value decreased to 1.4 mg/dl, and urine output returned to greater than 2000 ml per day. To date the patient has exhibited no significant side effects after over 4 months of sirolimus therapy and the withdrawal of corticosteroids.