A comparison of prednisolone and methylprednisolone for renal transplantation

Abstract

A large difference in immunosuppressive potency between methylprednisolone and prednisolone has been suggested in vitro. However, the selection of the best glucocorticoid for renal transplantation has been seldom considered so far. Thus, the present study was undertaken to compare therapeutic efficacy between prednisolone and methylprednisolone in renal transplantation. We studied 42 renal transplant recipients who were operated on between 1990 and 1994. The patients were divided into two treatment groups: a methylprednisolone/ cyclosporine group (n = 19) and a prednisolone/cyclosporine group (n = 23). Clinical outcome and drug side effects were compared retrospectively between the treatment groups 24-84 months after transplantation. The overall graft survival time in patients treated with methylprednisolone/cyclosporine was superior to that in patients treated with prednisolone/cyclosporine (p < 0.05). Among the recipients from cadaver donors, 5/16 (31.3%) treated with prednisolone required nephrectomy, whereas none of the 10 patients treated with methylprednisolone received nephrectomy (p < 0.01). An examination of the recipients from living related donors revealed that serum creatinine levels 24-36 months after operation were significantly lower in the methylprednisolone group (p < 0.05). Cyclosporine trough levels and glucocorticoid side effects were similar between the treatment groups. The results raised the possibility that methylprednisolone is superior to prednisolone when combined with cyclosporine for maintenance immunosuppressive therapy in renal transplantation.

Glucocorticoid receptors in lymphocytes and stability of kidney graft function

“…A few studies indicate that as yet unknown postreceptor events could be involved in glucocorticoid resistance of patients with rejection episodes [18,33]. In accordance with this are the published results showing a significantly positive correlation between lymphocyte resistance to glucocorticoids and the capacity of lymphocytes to produce cytokines [29,34]. The possible mechanisms include the presence of abnormal receptors in lymphocytes [22] or the antagonism of the suppressive effects of glucocorticoids on the immune system by the higher concentrations of cytokines [35,36] and the distinct classes of transcription factors [3].…”

“…The results of our studies and other groups [24,29] have demonstrated a significant influence of suboptimal cyclosporine dosage on the development of chronic rejection. Chronic rejection also occurred in patients maintained on optimal cyclosporine doses with the addi-184 tion of prednisone and azathioprine doses similar to those applied to patients with stable graft function.…”

“…Peripheral blood lymphocytes were obtained from heparinized fresh human blood samples by a discontinuous density gradient separation over Ficoll-Hypaque (Pharmacia, Uppsala, Sweden) as described previously [15,16,28,29]. The cells were washed with phosphate buffer saline, pH 7.2 and resuspended in RPMI 1640 medium to a final density of 1x10 8 cells/ml.…”

Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine

“…In one report, the suppressive potency of methylprednisolone in vitro on the blastogenesis of PBMCs from renal transplant recipients was found to be more than 10-folds superior to that of prednisolone [16]. Further, a retrospective clinical trial for the comparison of the benefits of methylprednisolone and prednisolone in combination with cyclosporine in 42 renal transplant recipients has been carried out [47]. The overall graft survival time in patients treated with methylprednisolone was significantly superior to that in patients treated with prednisolone, while the incidence and severity of the side effects of GCs and dose or blood concentration of cyclosporine coadministered did not differ between the groups [47].…”

“…Further, a retrospective clinical trial for the comparison of the benefits of methylprednisolone and prednisolone in combination with cyclosporine in 42 renal transplant recipients has been carried out [47]. The overall graft survival time in patients treated with methylprednisolone was significantly superior to that in patients treated with prednisolone, while the incidence and severity of the side effects of GCs and dose or blood concentration of cyclosporine coadministered did not differ between the groups [47]. These observations raise the possibility that methylprednisolone should be the first choice as a GC in renal transplantations.…”