Since the majority of acute rejection events occur in the first few weeks after that kidney transplantation, the study protocol specified that steroids should be tapered and withdrawn in the steroid withdrawal arm if no histological evidence of subclinical rejection was present at month 3. By this protocol, 52.6% of steroid withdrawal patients were steroid-free at month 6. This highlights the difficulty of withdrawing steroids at a later time point (i.e., after three months) compared to an early steroid-free regimen whereby patients received no oral steroids after transplantation. There was also a clinical requirement to introduce steroids before month 6 in 27.1% of patients in the steroid avoidance arm by month 6 (most frequently in response to suspected or confirmed acute rejection).

Consequently, there was considerable overlap in steroid administration between the two groups during months 6 to 36. Nevertheless the mean cumulative steroid dose during months 6 to 36 in the cohort randomized to steroid avoidance arm was 27% lower than that in the steroid group, a difference that approached statistical significance (P = 0.058). Data on adverse events should be interpreted in this context; that is, the greatest difference in steroid exposure between groups occurred during the first three months after transplantation and narrowed thereafter.

Thus, although both the metabolic effects of steroids such as hypertension, hyperlipidemia, diabetes mellitus, obesity and endothelial dysfunction, and other effects including osteoporosis and skin atrophy are well recognized [21], it is not unexpected that the between-group differences in the incidence of adverse events and serious adverse events with a suspected relation to steroids which were observed at month 6 [9] became nonsignificant over the period 6�C36 months after transplant. Additionally, Dacomitinib even the current extended follow-up period of 36 months is probably inadequate to detect the long-term benefit of steroids avoidance, particularly for cardiovascular disease. Recently, 10-year results were reported from a nonrandomized single-center analysis of adult primary kidney transplant patients in whom steroids were discontinued after postoperative day 5 [22]. Patients received rabbit antithymocyte globulin induction therapy, with a CNI (either CsA or tacrolimus) and mycophenolate mofetil or sirolimus. At 10 years after transplant, there was a significant reduction in steroid-related side effects compared to historical controls, with acceptable patient and graft survival. The current randomized, multicenter study confirms that steroid avoidance is also feasible in kidney transplant patients who receive IL-2RA induction, CsA, and early intensified EC-MPS.