Steroid withdrawal and donor-specific hyporeactivity after cadaveric renal allotransplantation on maintenance triple therapy

Background. Even in low doses, long-term steroid immunosuppression is known to cause serious complications. However, the safety of steroid withdrawal has not been proven in randomized clinical trials. This study examines donor-specific hyporesponsive transplant recipients before and after steroid withdrawal, to see if reduction in immunosuppresion was associated with consistent changes in antidonor immunological reactivity. Method. Using limiting dilution assays, the circulating precursor frequency of donor and third-party-reactive helper T lymphocytes (HTLpf) were determined in 21 consecutive cadaveric renal allograft recipients on standard triple therapy, before (pre-tx) and at different time points after transplantation (post-tx). Patients were selected for steroid withdrawal by clinical criteria (stable graft function and no or only one very mild rejection episode). Results. Of 21 patients studied, steroids were successfully withdrawn in nine (steroid withdrawn group, SWG) for at least 187 days (mean: 380+/-168.5), and were not withdrawn in 12 patients (steroid continued group, SCG). In the SWG seven of nine patients developed at least fivefold reduction of post-tx donor-reactive HTLpf (range 5-17), relative to pre-tx, as compared to two of twelve patients in the SCG, P=0.01. In both groups, the third-party-reactive HTLpf in most of these patients remained largely unchanged throughout the study period. In the SWG, no significant difference of serum creatinine level was found before and at 6 months after steroid withdrawal (mean: 138+/-24 rer sus 132+/-40, P=0.45). Conclusion. Patients who developed donor-specific hyporeactivity as evidenced by low donor-reactive HTLpf had stable graft function and stable HTLpf levels after complete steroid withdrawal.