Sirolimus rescue therapy for refractory renal allograft rejection - Case report

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 antirejection 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 mi 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 Tc-99m-DTPA scan. Within 6 weeks the patient's sCr value decreased to 1.4 mg/dl, and urine output returned to greater than 2000 mi per day. To elate the patient has exhibited no significant side effects after over 4 months of sirolimus therapy and the withdrawal of corticosteroids.