Cyclosporin maintenance monotherapy after renal transplantation - What factors predict success?

The use of cyclosporin monotherapy as maintenance immunosuppression in prim ary cadaveric renal transplant recipients is not popular except in a few Eu ropean centres. Corticosteroid withdrawal is becoming more popular, and is usually attempted with the newer immunosuppressants which have a more corti costeroid-sparing effect than cyclosporin. The adverse effects and morbidit y associated with maintenance regimens consisting of 2 or 3 immunosuppressi ve drugs are well known, but the potential benefits of cyclosporin monother apy must be balanced against an increased risk of graft loss by rejection. We selected patients for a trial of corticosteroid withdrawal and subsequen t cyclosporin monotherapy. These patients received an individually designed immunosuppressive regimen with careful control of cyclosporin trough conce ntrations. The cyclosporin formulations used were its original oil-based so lution or gelatin capsule (Sandimmun(R), Sandimmune(R)) until mid-1996 and then the microemulsion formulation (Neoral(R)). Corticosteroid withdrawal was attempted in 89% of patients with a graft fun ctioning at 3 months after transplantation and was effective in 88% of them . At a mean follow-up time of 98 +/- 23 months, 69% of grafts were function ing and 92% of patients were alive. 50% of patients with a functioning graf t were receiving long term cyclosporin monotherapy. Mild rejection episodes occurred in 6% of patients receiving cyclosporin monotherapy per year of t reatment, and chronic rejection caused graft loss in 1.4% of patients per y ear of treatment. Comparison of successful and unsuccessful outcomes allows us to define favo urable predictive factors. For corticosteroid withdrawal these are: older r ecipient age, lower creatininaemia at months 6 and 8 and higher trough cycl osporin concentrations at month 6. For cyclosporin monotherapy these are: l ater timing of azathioprine withdrawal, recipient age >25 years, donor age less than or equal to 40 years, creatininaemia less than or equal to 125 mu mol/L at initiation of monotherapy and no rejection episode before initiat ion of monotherapy. We have observed a low incidence of nonmelanoma skin cancers and of squamou s-cell carcinoma in our series. This is perhaps the result of the azathiopr ine-sparing effects of the regimen (7 azathioprine-free years per patient w ith successful cyclosporin monotherapy, and 4 azathioprine-free years per p atient with unsuccessful monotherapy). This important point will need furth er studies but is encouraging. Maintenance cyclosporin monotherapy is feasible and probably useful in sele cted primary graft recipients without deleterious effects on overall result s in terms of graft and patient survival. Careful patient selection using t he predictive factors we have defined should make cyclosporin monotherapy m ore effective, allowing the present 57% success rate at 5 years post-transp lantation to be increased by 15 or 20%.