Gj. Bouma et al., IN-VITRO SENSITIVITY TO PREDNISOLONE MAY PREDICT KIDNEY REJECTION AFTER STEROID WITHDRAWAL, Transplantation, 62(10), 1996, pp. 1422-1429
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ssion of cyclosporine and steroids and a group to be withdrawn from st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, Patients withdrawn from steroids were monitored closely and when a b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.