A RANDOMIZED TRIAL COMPARING CYCLOSPORINE AND STEROIDS WITH CYCLOSPORINE, AZATHIOPRINE, AND STEROIDS IN CADAVERIC RENAL-TRANSPLANTATION

Background. In renal transplantation, triple-drug therapy (low-dose cy closporine [CsA] combined with azathioprine plus steroids) has been re placing double-drug therapy (CsA plus steroids) in clinical practice w ithout much evidence in favor of either therapy. Previous trials compa ring the two immunosuppressive regimens gave conflicting results. We a ttempted to determine whether triple therapy is at least equivalent to double therapy. Methods. A randomized trial was performed in 250 adul t cadaveric renal transplant recipients, comparing double therapy (CsA [10 mg/kg/day] plus prednisone) with triple therapy (CsA [6 mg/kg/day ] plus azathioprine plus prednisone). The median follow-up time was 93 0 days. Results. The incidence of acute rejection episodes refractory to treatment was 11% in double therapy and 4% in triple therapy (relat ive risk reduction: 64%; 95% confidence interval: 5-100%; P=0.035). Pa tients in the double therapy group required more intensive antirejecti on treatment, and their pathologic lesions were more severe, The propo rtion of patients with acute rejection was similar (double therapy: 45 % vs, triple therapy: 40%) as was the incidence of chronic renal dysfu nction (double therapy: 17% vs, triple therapy: 15.5%), the I-year gra ft survival (double therapy: 71% vs, triple therapy: 83%, P=0.089), an d patient survival (double therapy: 94% vs, triple therapy: 93%). In 2 9 patients (23%), 35 episodes of azathioprine-induced leukopenia were recorded, and in 9 of them azathioprine had to be discontinued, The in cidence of other adverse events did not differ between the groups. Con clusions. Triple therapy caused fewer episodes of refractory acute rej ection episodes and was as efficacious and safe as double therapy.