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• W2085672564 abstract "We read with interest the meta-analysis Pascual et al. (1) of steroid withdrawal between 3 and 6 months posttransplant. The results of this meta-analysis broadly agree with our own recently reported conclusions that although there is an increased risk of acute rejection (AR) with steroid withdrawal, this does not seem to translate to an increase in graft dysfunction or graft loss (2). In contrast to our meta-analysis, Pascual et al. conclude that this increase in AR rate is only seen with cyclosporine as the concomitant calcineurin inhibitor and not with tacrolimus. Their conclusion should be interpreted with some caution as the data on which it is drawn are limited. Significant interaction between calcineurin inhibitor subgroups is only seen with biopsy-proven (not clinically suspected) AR, and in their analysis, the tacrolimus subgroup is limited to a single study. However, this would seem to make some clinical sense as tacrolimus has been shown to be associated with less AR and superior graft survival compared with cyclosporine (3). Thus steroid withdrawal in the context of superior maintenance immunosuppression should yield more success. Nonetheless, we found no significant interaction between maintenance immunosuppression and the outcomes of steroid withdrawal protocols in our large analysis. We were also interested in the commentary about both studies in the same issue from Sprangers and Vanrenterghem (4), who come to the conclusion that early steroid withdrawal, that is, in the first week (as suggested in the Kidney Disease: Improving Global Outcomes [KDIGO] guidelines) is less safe than withdrawal beyond 3 months after transplantation. Our meta-analysis of the available data does not support this conclusion. It should be noted that the interpretation of Sprangers and Vanrentergham of the AR data in our analysis is incorrect. They imply that because there is a significant increase in the risk of AR in all groups of patients withdrawn from steroids before 1 year posttransplant, but not in the group of patients withdrawn after 1 year, that it is safer to withdraw steroids beyond 1 year posttransplant. If one examines Figure 2 in our article in more detail, it can be seen that this is not necessarily true—there are significantly less patients in the group withdrawn beyond 1 year posttransplant making the confidence interval (CI) for this relative risk wide and indeed overlapping all the other subgroups. Formal statistical test for interaction demonstrates no significant difference between this subgroup and any other. Furthermore, a mixed-effects analysis incorporating time of steroid withdrawal as a continuous linear moderator variable demonstrates no interaction with the risk of AR. In fact, none of our data support an effect of withdrawal time on the risk of AR, graft function, or graft or patient survival after renal transplantation. In particular, if one compares the subgroups withdrawn from steroids within 7 days (induction group) and those withdrawn from 7 days to 1 year posttransplant (early withdrawal), there is no evidence that earlier withdrawal confers greater risk. In particular, hazard ratio for graft loss including death with a functioning graft is 0.81 (95% CI 0.60–1.11, eight studies) in the induction group and 1.22 (95% CI 0.88–1.68, 8 studies) in the early withdrawal group. Hazard ratio for graft loss excluding death with a functioning graft is 0.98 (95% CI 0.17–1.43, 8 studies) in the induction group and 1.52 (95% CI 1.04–2.22, 8 studies) in the early withdrawal group. If anything, these data suggest a trend toward slightly higher risk of graft loss with withdrawal after 7 days, although the differences between these subgroups do not reach statistical significance. Similarly, there is no effect of withdrawal time on renal function measured by creatinine clearance or serum creatinine levels, with marginally worse function seen with steroid withdrawal in all groups. Therefore, on the basis of our data, we believe that withdrawal of steroids within the first week after transplantation is safe in low-risk recipients, as per the KDIGO guidelines. However, in contrast to the KDIGO guidelines, we also believe that withdrawal of steroids in low-risk recipients after the first week is also safe. Data regarding complete steroid avoidance are minimal, and this cannot be recommended without further evidence. Simon R. Knight1,2 Peter J. Morris1 1 Centre for Evidence in Transplantation Royal College of Surgeons of England London, United Kingdom 2 Oxford Transplant Centre Churchill Hospital Oxford, United Kingdom" @default.
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• W2085672564 date "2011-03-15" @default.
• W2085672564 modified "2023-10-17" @default.
• W2085672564 title "Steroid Avoidance or Withdrawal in Renal Transplantation" @default.
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• W2085672564 doi "https://doi.org/10.1097/tp.0b013e318208e6d9" @default.
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