IN-VITRO SENSITIVITY TO PREDNISOLONE MAY PREDICT KIDNEY REJECTION AFTER STEROID WITHDRAWAL

A maintenance immunosuppressive regimen of cyclosporine and steroids a fter renal transplantation has proven to be a successful policy to obt ain longterm graft survival, However, serious side-effects are associa ted with this therapy; these include an increased risk for infections, cancer, and cardiovascular morbidity and mortality, Therefore, this p ilot study was conducted to investigate the possibility of reducing th e immunosuppressive load after transplantation, To this end, we tried to develop an in vitro assay to predict graft rejection after withdraw ing steroids from the immunosuppressive therapy, Patients who had stab le renal function at least one year after transplantation were randoml y divided into a group that continued to receive standard immunosuppre ssion of cyclosporine and steroids and a group to be withdrawn from st eroid therapy, the latter group being the subject of the present study , Patients withdrawn from steroids were monitored closely and when a b iopsy-proven rejection occurred, steroid treatment was reestablished, Blood was collected from patients preceding steroid withdrawal and at fixed time points thereafter, In case of suspected rejection, blood wa s also taken before biopsy, before steroid treatment was reestablished , In the in vitro limiting dilution analysis-assays cytotoxic T lympho cyte precursor frequencies directed against kidney donor HLA-antigens were determined, in the absence or presence of cyclosporine and severa l concentrations of prednisolone and the combination of these agents, Confirming earlier results, we found that the number of cyclosporine-r esistant cytotoxic T lymphocytes increased prior to a rejection crisis , while they did not change or even decreased in patients who retained normal graft function after steroid withdrawal, More importantly, the results show that 10(-7) M prednisolone in vitro differentially affec ted donor-specific cytotoxic T lymphocyte precursor frequencies in pat ients who experienced a rejection crisis after steroid withdrawal, com pared with those who remained to do well, This heterogeneity could be detected before the start of steroid withdrawal. Therefore, we conclud e that the present data justify a prospective clinical trial to invest igate the possible application of this in vitro assay to predict for w hich patients steroid withdrawal might be considered.