Cyclosporine withdrawal in renal transplant recipients maintained on azathioprine, prednisone and cyclosporine

The introduction of cyclosporine as an immunosuppressant in clinical organ transplantation has improved the results with respect to patient and graft survival (1, 2, 3). However, its long-term renal toxicity and other wide-ranging adverse reactions are its limiting factors. In the Kuwait renal transplantation programme cyclosporine (CsA) was introduced in cadaver renal transplantation in 1983 and in HLA mismatched living donor transplantation in 1988 as one of the constituents of triple drug prophylactic immunosuppressive therapy, together with azathioprine and prednisone. Despite the small maintenance doses of CsA, many of our patients developed serious side effects such as nephrotoxicity, hypertension, hirsutism, tremors, gingival hypertrophy and hepatoxicity, which in turn contributed to non-compliance with regard to cyclosporine intake. This observation together with previous reports on cyclosporine withdrawal prompted us to carry out a randomized prospective clinical trial of cyclosporine withdrawal in renal transplant recipients with stable graft function on triple therapy for at least 1–2 years after transplantation. The aim of this study was to determine the effect of cyclosporine withdrawal on renal graft function and the possible benefit of ameliorating the toxic effects after withdrawal of the drug. Additionally the method of CsA withdrawal, either gradual over a period of few weeks or abrupt discontinuation, was also assessed.