MAINTENANCE CYCLOSPORINE MONOTHERAPY AFTER RENAL-TRANSPLANTATION - CLINICAL PREDICTORS OF LONG-TERM OUTCOME

Background. There is considerable debate about whether maintenance cyc losporin (CsA) monotherapy is advisable or not in renal transplantatio n. Methods. Between August 1984 and December 1989, 463 adult patients received a first cadaver graft. initial immunosuppression was sequenti al: antilymphocyte or antithymocyte globulins (10-14 days), prednisone and azathioprine were combined and CsA was introduced (6-8 mg/kg/day) when the antilymphocyte or antilymphocyte globulins were discontinued . When the graft function was stable and the peak of preformed lymphoc ytotoxic antibodies was less than or equal to 25% and/or the number of rejection episodes was less than or equal to 1, the steroid therapy w as stopped within 1.5-3 months after transplantation, and azathioprine within 3-12 months. Patients with both anti HLA antibodies >25% and m ore than one rejection episode were excluded. Cyclosporin doses were a dapted for whole-blood trough levels between 100 and 200 ng/ml (monocl onal antibody radioimmunoassay or high-performance liquid chromatograp hy). Cyclosporin monotherapy was attempted in 234 of the 463 patients. Results. At the end of the investigation in January 1993 (follow-up t ime >36 months, mean 60.5+/-4.5 months), 135 patients were receiving C sA without steroids or azathioprine. The 99 CsA monotherapy failures w ere due to rejection episodes in 48 cases, CsA A nephrotoxicity in 26 cases, and other causes in 25 cases, including five deaths and four wi th poor compliance. Renal function was stable in patients with success ful CsA monotherapy: mean creatininaemia was 124+/-10 mu mol/l at the time of CsA monotherapy inclusion and 129+/-10 mu mol/l at the end of follow-up (mean time of CsA monotherapy 52+/-6 months). The parameters for predicting monotherapy success were age (43.2 ver sus 37.8, P=0.0 014), timing of trial inclusion greater than or equal to 6 months post -transplant (7.9+/-3 versus 5.3+/-3.1 months, P=0.04), and excellent a nd stable renal function at the time of inclusion (124+/-10 versus 145 +/-32 mu mol/l, P < 0.001).Conclusions. Maintenance CsA monotherapy wa s effective in 58% of low-immunological-risk first-graft patients and probably did not jeopardize overall results of our first grafts: patie nt and graft survival were respectively 90 and 73% at 6 years. We prop ose this policy to avoid long-term complications of glucocorticoid and azathioprine in selected compliant recipients with low immunological risk, follow-up time posttransplantation >6 months, and stable creatin inaemia levels.