A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-Risk Kidney Transplant Recipients
Steroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft survival. In the SAILOR study, we investigated the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes on the current standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil (MMF).
METHODS:In this 2-year, multicenter, open-label trial, a total of 222 patients were randomized to receive either steroid avoidance protocol (tacrolimus/MMF/antithymocyte globulin [ATG] induction [n = 113]) or steroid maintenance protocol (tacrolimus/MMF/prednisolone/basiliximab-induction [n = 109]).
RESULTS:At 1 year, no significant differences were found between steroid avoidance and steroid maintenance arms in the incidence of PTDM, the primary end point (12.4% vs. 18.3%, respectively, P = 0.30, CI: 16.3-4.4), or in overall biopsy-proven rejections (15% vs. 13.8%, respectively, P = 0.85). At 2 years, the composite end point of freedom from acute rejection, graft loss, and death (81% vs. 85%, respectively, P = 0.4), kidney function, or adverse events was comparable between the 2 arms. Moreover, 63.9% of the patients in the steroid avoidance arm remained free from steroids at 2 years.
CONCLUSION:The SAILOR study provides further evidence for the feasibility, safety, and efficacy of early steroid-free treatment at 2 years in immunologically low-risk kidney recipients with tacrolimus/MMF maintenance regimen.
CET Conclusion
| Reviewer: | Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford |
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| Conclusion: | This multicentre RCT investigated the safety of complete steroid avoidance with maintenance steroid therapy following renal transplantation in low-risk patients. Patients undergoing avoidance received ATG induction, whereas those undergoing maintenance therapy received basiliximab. There were no significant differences in risk of acute rejection, graft or patient survival, or incidence of post-transplant diabetes (PTDM). This leads the authors to conclude that in this patient population, steroid avoidance is safe when used in conjunction with ATG induction and Tac/MMF. There are some points of note. Firstly, 36% of patients in the steroid avoidance arm ended up on oral steroids at 2 years, diluting any potential benefit in intent-to-treat analysis. Secondly, the initial power calculation estimated a risk of PTDM in the control arm of 36%, whereas the observed rate was only 18%, leading to an underpowered study. Finally, the maintenance steroid dose in the control arm after 6 months was a relatively low average of 5-6mg/day. Post-hoc analysis of our own previous meta-analysis suggested that risk of diabetic complications related to steroid maintenance dose, with the benefits of avoidance compared to low-dose steroids being more limited than compared to higher doses. |
Methodological quality
| Jadad score | 3 |
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| Allocation concealment | YES |
| Data analysis | MODIFIED INTENTION TO TREAT |
Study Details
| Aims: | The aim of this study was to investigate whether complete steroid avoidance with tacrolimus/ mycophenolate mofetil (MMF)/ antithymocyte globulin (ATG) induction in immunologically low-risk kidney transplant patients without diabetes leads to a reduction in the incidence of post-transplant diabetes mellitus (PTDM) with good efficacy and safety in two years, in comparison to the standard steroid maintenance regimen. |
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| Interventions: | Participants were randomly assigned to either the steroid avoidance arm or the steroid maintenance arm. |
| Participants: | 224 low immunological risk kidney transplant recipients. |
| Outcomes: | The primary outcome was the incidence of PTDM within one year following transplantation. Secondary outcomes included incidence of PTDM and use of antidiabetic agents at 2 years; incidence of biopsy-proven rejection; composite measure of freedom from acute rejection, graft loss, and death; kidney function; occurrence of infections; major cardiovascular events and malignancies; mean doses, mean area under the curve (AUC) of doses, trough levels, and AUCs for immunosuppressants; and use of antihypertensive and lipid-lowering agents. |
| Follow Up: | 2 years |
Metadata
| Funding: | Industry funding and Non-industry funding |
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| Publication type: | Randomised Controlled Trial |
| Trial registration: | EudraCT - 2012-000451-13 |
| Organ: | Kidney |
| Language: | English |
| Author email: | jana.ekberg@vgregion.se |
| MeSH terms: | Kidney Transplantation |