A randomized prospective trial comparing cyclosporine monotherapy with triple-drug therapy in renal transplantation.

In a prospective trial 151 recipients of renal transplants were randomly assigned to treatment with CsA alone (74 patients) and to low dose of AZA, prednisolone, and CsA (77 patients). At two years, graft survival was 84% for the monotherapy and 90% for the triple therapy. This difference was not statistically significant. The number of rejection episodes was similar in the two groups, but the severity of rejection was significantly worse among the patients on monotherapy. More kidneys were lost because of rejection (6 versus 3), and a higher number of methylprednisolone pulses was used for treating rejection (5.2 +/- 2.3 versus 4.3 +/- 2.9; P = 0.0077). CsA nephrotoxicity episodes were more frequent among patients on monotherapy (23 versus 7; P less than 0.02). Infectious episodes were equally distributed between the two groups. Creatinine clearance was poorer in the monotherapy-treated patients at the third month (42 +/- 16 ml/min versus 48 +/- 15 ml/min; P = 0.02), but no differences were observed between the two groups since the sixth month after transplantation. Many patients on monotherapy required changes in maintenance therapy. In fact, one patient was switched to conventional immunosuppression because of Cremophor-induced anaphylaxis. Another patient who developed Kaposi's sarcoma 4 months after surgery was switched to steroids alone. Excluding 5 patients who lost their grafts a few days after transplantation, only 30 of 74 patients (40%) could be kept without steroids. We conclude that both the therapeutic protocols can give good results in renal allotransplantation; however, monotherapy could create some problems in keeping the balance between drug toxicity and significant immunosuppression. On the contrary, triple therapy is easier to handle, especially in the early posttransplant period when the differential diagnosis between acute rejection and CsA-related nephrotoxicity can be difficult even for a skilled clinician.