Cyclosporin maintenance monotherapy after renal transplantation: what factors predict success?
The use of cyclosporin monotherapy as maintenance immunosuppression in primary cadaveric renal transplant recipients is not popular except in a few European centres. Corticosteroid withdrawal is becoming more popular, and is usually attempted with the newer immunosuppressants which have a more corticosteroid-sparing effect than cyclosporin. The adverse effects and morbidity associated with maintenance regimens consisting of 2 or 3 immunosuppressive drugs are well known, but the potential benefits of cyclosporin monotherapy must be balanced against an increased risk of graft loss by rejection. We selected patients for a trial of corticosteroid withdrawal and subsequent cyclosporin monotherapy. These patients received an individually designed immunosuppressive regimen with careful control of cyclosporin trough concentrations. The cyclosporin formulations used were its original oil-based solution or gelatin capsule (Sandimmun, Sandimmune )until mid-1996 and then the microemulsion formulation (Neoral). Corticosteroid withdrawal was attempted in 89% of patients with a graft functioning 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 functioning and 92% of patients were alive. 50% of patients with a functioning graft were receiving long term cyclosporin monotherapy. Mild rejection episodes occurred in 6% of patients receiving cyclosporin monotherapy per year of treatment, and chronic rejection caused graft loss in 1.4% of patients per year of treatment. Comparison of successful and unsuccessful outcomes allows us to define favourable predictive factors. For corticosteroid withdrawal these are: older recipient age, lower creatininaemia at months 6 and 8 and higher trough cyclosporin concentrations at month 6. For cyclosporin monotherapy these are: later timing of azathioprine withdrawal, recipient age >25 years, donor age <or=40 years, creatininaemia <or=125 micromol/L at initiation of monotherapy and no rejection episode before initiation of monotherapy. We have observed a low incidence of nonmelanoma skin cancers and of squamous-cell carcinoma in our series. This is perhaps the result of the azathioprine-sparing effects of the regimen (7 azathioprine-free years per patient with successful cyclosporin monotherapy, and 4 azathioprine-free years per patient with unsuccessful monotherapy). This important point will need further studies but is encouraging. Maintenance cyclosporin monotherapy is feasible and probably useful in selected primary graft recipients without deleterious effects on overall results in terms of graft and patient survival. Careful patient selection using the predictive factors we have defined should make cyclosporin monotherapy more effective, allowing the present 57% success rate at 5 years post-transplantation to be increased by 15 or 20%.
Touchard
G
G
Nephrology Unit, Centre Hospitalier Universitaire, Poitiers, France.
Verove
C
C
Bridoux
F
F
Bauwens
M
M