Effectiveness of minimal dosage cyclosporine in limiting toxicity and rejection

The optimal dose of cyclosporine to achieve minimal toxicity and adequate control of rejection remains undetermined. We initiated our program with an immunosuppressive protocol designed to reduce drug toxicity, to reduce early severe rejection, and to provide adequate long-term immunosuppression. Because of increasing reports of nephrotoxicity associated with cyclosporine, we adopted a protocol of low-dose cyclosporine combined with steroids and equine antithymocyte globulin. The mean preoperative creatinine was 0.12 +/- 0.08 mmol/L and by 1 year after transplant was 0.13 +/- 0.04 mmol/L. Cyclosporine dose at 1 year was 5 +/- 2 mg/kg/day, and the serum cyclosporine level was 120 +/- 40 ng/ml. However, at 1 year 85% of the patients were hypertensive. The incidence of rejection in the first year after transplantation was 1.46 episodes per patient. Incidence of infection was 0.85 episodes per patient. The 3-month survival was 91%, and the actuarial 1-year survival was 76%. Seventy percent of our mortality was due to rejection, and four patients suffered significant graft damage in the period 3 months to 1 year, two requiring retransplantation. Although these low doses of cyclosporine have reduced nephrotoxicity and infectious complications, hypertension remains a significant problem. Moreover, although survival is acceptable, the incidence of graft rejection causing death or loss of function is of concern. This may indicate that cyclosporine at this dosage needs supplementation by a third immunosuppressive agent such as azathioprine.