A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation

Transplantation. 2000 May 15;69(9):1861-7. doi: 10.1097/00007890-200005150-00021.

Abstract

Background: Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection.

Methods: One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years.

Results: After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B.

Conclusion: Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Aged
  • Azathioprine / administration & dosage*
  • Creatinine / blood
  • Cyclosporine / administration & dosage
  • Cyclosporine / therapeutic use*
  • Female
  • Graft Rejection / prevention & control*
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Prospective Studies

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Cyclosporine
  • Creatinine
  • Azathioprine