Maintenance cyclosporin monotherapy after renal transplantation--clinical predictors of long-term outcome.

BACKGROUND

There is considerable debate about whether maintenance cyclosporin (CsA) monotherapy is advisable or not in renal transplantation.

METHODS

Between August 1984 and December 1989, 463 adult patients received a first cadaver graft. Initial immunosuppression was sequential: 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 antithymocyte globulins were discontinued. When the graft function was stable and the peak of preformed lymphocytotoxic antibodies was < or = 25% and/or the number of rejection episodes was < or = 1, the steroid therapy was stopped within 1.5-3 months after transplantation, and azathioprine within 3-12 months. Patients with both anti HLA antibodies > 25% and more than one rejection episode were excluded. Cyclosporin doses were adapted for whole-blood trough levels between 100 and 200 ng/ml (monoclonal antibody radioimmunoassay or high-performance liquid chromatography). Cyclosporin monotherapy was attempted in 234 of the 463 patients.

RESULTS

At the end of the investigation in January 1993 (follow-up time > 36 months, mean 60.5 +/- 4.5 months), 135 patients were receiving CsA without steroids or azathioprine. The 99 CsA monotherapy failures were due to rejection episodes in 48 cases, CsA A nephrotoxicity in 26 cases, and other causes in 25 cases, including five deaths and four with poor compliance. Renal function was stable in patients with successful CsA monotherapy: mean creatininaemia was 124 +/- 10 mumol/l at the time of CsA monotherapy inclusion and 129 +/- 10 mumol/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 versus 37.8. P = 0.0014), timing of trial inclusion > or = 6 months post-transplant (7.9 +/- 3 versus 5.3 +/- 3.1 months, P = 0.04), and excellent and stable renal function at the time of inclusion (124 +/- 10 versus 145 +/- 32 mumol/l, P < 0.001).

CONCLUSIONS

Maintenance CsA monotherapy was effective in 58% of low-immunological-risk first-graft patients and probably did not jeopardize overall results of our first grafts: patient and graft survival were respectively 90 and 73% at 6 years. We propose this policy to avoid long-term complications of glucocorticoid and azathioprine in selected compliant recipients with low immunological risk, follow-up time post-transplantation > 6 months, and stable creatininaemia levels.