SIMULTANEOUS QUADRUPLE IMMUNOSUPPRESSION WITH CYCLOSPORINE INDUCTION THERAPY IN HIGH-RISK RENAL-TRANSPLANT RECIPIENTS

High risk renal transplant recipients experience excess graft loss des pite overall improvements in the results of cadaveric renal transplant ation. We evaluated a novel immunosuppression regimen consisting of si multaneous administration of OKT3, cyclosporine, azathioprine and pred nisone. 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. or ally or 3 mg./kg. intravenously per day) starting from the day of tran splant regardless of graft function; 5 mg. OKT3 per day for 10 to 14 d ays starting intraoperatively; 5 mg./kg. azathioprine per day for 2 da ys, then 1.5 mg./kg. per day and adjusted according to white blood cel l 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 wh en serum creatinine was less than 3 mg./dl. The cyclosporine whole blo od levels (measured by high performance liquid chromatography) were ma intained between 250 and 400 ng./ml. in the first 3 months. Followup e valuations 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) exper ienced 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 rejecti on) were treated with antilymphoblast globulin rescue therapy for 10 t o 14 days. Symptomatic cytomegalovirus pneumonia occurred in 3 patient s (25%). There were no deaths or graft losses. No case of malignancy w as 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 s imultaneous quadruple immunosuppressive regimen that includes inductio n cyclosporine and OKT3 is a highly effective therapy for high risk pa tients, 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.