Donor-Specific HLA Antibodies in a Cohort Comparing Everolimus with Cyclosporine After Kidney Transplantation
Liefeldt L, Brakemeier S, et al.American Journal of Transplantation, 12(5):1192-8, 2012.
Aims
To compare the effect of conventional cyclosporine-based therapy with a calcineurin inhibitor free, everolimus-based regimen on the formation of donor-specific HLA antibodies (DSA).
Interventions
Continue cyclosporine versus switch from cyclosporine to everolimus. All patients received enteric-coated mycophenolate sodium (MPS) and steroids.
Participants
127 kidney transplant recipients who participated in ZEUS trial and 142 kidney transplant patients in the CRAD001ADE13-trial.
Outcomes
The incidence of de novo DSA, time to first detection of DSA, first biopsy-proven antibody-mediated rejection (AMR), graft survival, serum creatinine and proteinuria. Factors included in the regression analyses for the development of de novo DSA and AMR included underlying renal disease, recipient age, gender, waiting time, immunosuppressive regimen (everolimus versus cyclosporine), reduced MPS-dose, number of mismatches, donor type, biopsy-proven acute rejection(s) within the first year, number of kidney transplants (second versus first) and patient’s compliance.
Follow-up
5 years
CET Conclusions
In this subgroup analysis of two single centre randomised controlled trials in which patients were randomised to switch from cyclosporine to everolimus or continue on cyclosporine at either 3 months or 4.5 months after transplantation, the authors report that the development of donor specific antibodies was more frequent in the patients who were converted to everolimus. In addition the incidence of antibody mediated rejection was more common in the everolimus intervention arm.
Data analysis
Strict intention-to-treat analysis
Quality notes
This is a subgroup analysis of a previous publication of the same RCT: Budde K, Becker T, Arns W et al, ZEUS Study Investigators. Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de novo kidney transplants: An open-label, randomised, controlled trial. Lancet 2011; 377: 837–847 The methodological quality assessment was based on the previous publication.
Trial registration
NCT00154310 (ClinicalTrials.gov) & NCT00514514 (ClinicalTrials.gov)