Simultaneous quadruple immunosuppression with cyclosporine induction therapy in high risk renal transplant recipients

High risk renal transplant recipients experience excess graft loss despite overall improvements in the results of cadaveric renal transplantation. We evaluated a novel immunosuppression regimen consisting of simultaneous administration of OKT3, cyclosporine, azathioprine and prednisone. Of the 12 high risk patients studied 5 received 2 transplants, 1 received 3 transplants and 8 had peak panel reactive antibodies of greater than 60%. The protocol consisted of cyclosporine (7 mg./kg. orally or 3 mg./kg. intravenously per day) starting from the day of transplant regardless of graft function; 5 mg. OKT3 per day for 10 to 14 days starting intraoperatively; 5 mg./kg. azathioprine per day for 2 days, then 1.5 mg./kg. per day and adjusted according to white blood cell counts, and prednisone taper at 2 to 0.4 mg./kg. per day on day 10. The dose of cyclosporine was increased to 14 mg./kg. per day orally when serum creatinine was less than 3 mg./dl. The cyclosporine whole blood levels (measured by high performance liquid chromatography) were maintained between 250 and 400 ng./ml. in the first 3 months. Followup evaluations ranged from 3 to 28 months (median 8.5). Seven patients (58.3%) had acute tubular necrosis and required dialysis support for 2 to 5 weeks. Six patients (including 5 with acute tubular necrosis) experienced 1 episode of acute rejection in the first 3 months (2 of these were due to accelerated vascular rejection). Two rejections responded to pulse steroid treatment, while 4 (including 2 with vascular rejection) were treated with antilymphoblast globulin rescue therapy for 10 to 14 days. Symptomatic cytomegalovirus pneumonia occurred in 3 patients (25%). There were no deaths or graft losses. No case of malignancy was observed to date. The serum creatinine is less than 2 mg./dl. in 9 patients, and 2.5 to 2.9 mg./dl. in the remaining 3. We conclude that simultaneous quadruple immunosuppressive regimen that includes induction cyclosporine and OKT3 is a highly effective therapy for high risk patients, yielding excellent short-term and intermediate success rates. Long-term results of this regimen, including neoplastic potentiation, cannot be addressed because of the limited followup of these patients.