CLINICAL RELEVANCE OF GLUCOCORTICOID PHARMACODYNAMICS IN KIDNEY TRANSPLANTATION

Recent articles by Bouma et al. (Transplantation 1996; 62: 1422 [1]) and Girardin and St-Louis (Transplantation 1996; 62: 1377 [2]) have discussed the clinical significance of glucocorticoid pharmacodynamics assessed by antilymphocyte action in kidney transplantations. In vitro sensitivity to prednisolone may predict allograft rejection during the early phases of transplantation (3) or after glucocorticoid withdrawal (1), whereas in vitro preoperative lymphocyte response to methylprednisolone may not predict the occurrence of cellular rejection during the first month after grafting (2). These observations seem to be controversial; however, we consider that the correlations between in vitro sensitivity to glucocorticoid and clinical outcomes may be observed only when the patients were treated with prednisolone but not with methylprednisolone. We could not find patients who were hyper-resistant to methylprednisolone in our assay procedure, but approximately 26% of the recipients who we examined showed hyper-resistance to prednisolone (3). According to our preliminary data, graft survival or other clinical data in methylprednisolone-treated patients was significantly superior to that in prednisolone-treated patients (our unpublished data). Prednisolone potency in vitro was less than 1/10 that of methylprednisolone (3). Moreover, IC50 of prednisolone on the blastogenesis of lymphocytes individually deviated from 1 to 10,000 ng/ml, whereas deviation of methylprednisolone IC50 was smaller than that of prednisolone (3). Therefore, the sensitivity and specificity of the test may be relatively poor at detecting methylprednisolone-resistant patients, but the sensitivity and specificity were enough to detect the patients who were hyper-resistant to prednisolone. Among some clinically accepted glucocorticoids, prednisolone and methylprednisolone have been alternatively used; however, selection of the best glucocorticoids for kidney transplantations on the basis of any scientific background has been little considered so far. The general concept for clinical potency of glucocorticoids is that methylprednisolone is 25% more potent than prednisolone according to the anti-inflammatory effects of these glucocorticoids (4). However, the unexpectedly strong immunosuppressive potency of methylprednisolone in vitro (3) raised the possibility that methylprednisolone could be a first choice as a glucocorticoid for kidney transplantations. Toshihiko Hirano1,2; Kitaro Oka1; Hironori Takeuchi3; Koichi Kozaki3; Naoto Matsuno3; Takeshi Nagao3; Masami Kozaki3 Department of Clinical Pharmacology; Tokyo College of Pharmacy; Hachioji Medical Center; Tokyo Medical College; Hachioji, Tokyo