15-year follow-up of a multicenter, randomized, calcineurin inhibitor withdrawal study in kidney transplantation.
Roodnat JI, Hilbrands LB, Hene RJ, et al.Transplantation 2014; 98(1): 47-53
Aims
This long term study aimed to evaluate the effects of calcineurin inhibitor (CNI) withdrawal in renal transplant patients from a study conducted 15 years ago.
Interventions
Patients were administered mycophenolate mofetil (MMF), cyclosporine A (CsA) and prednisone (Pred). Six months after transplantation patients received either MMF and Pred (CsA was stopped 2-9 weeks after randomisation), MMF and CsA (Pred was stopped 10 weeks after randomisation) or a continuation of MMF, CsA and Pred.
Participants
212 patients transplanted with a kidney between 1997-1999.
Outcomes
The primary outcomes were graft and patient survival in the three groups 15 years post transplant. The secondary outcomes included causes of graft failure, death and prevalence of cardiovascular disease and malignancy.
Follow-up
15 years.
CET Conclusions
This paper reports long-term follow-up from a 3-arm trial comparing cyclosporine withdrawal, steroid withdrawal and continuation of triple therapy 6 months following renal transplantation. At 15 years, no difference in graft or patient survival was seen between groups, although there is numerically inferior survival in the CNI withdrawal group (67% vs 81%), which the study may not be powered to show. Of interest, there was a strong trend toward a reduction in cardiovascular disease in the steroid withdrawal group, in keeping with previous meta-analyses, which demonstrate a reduction in cardiovascular risk factors. This paper shows the power of completing long-term follow-up by linking to registry data, allowing extended follow-up without the additional costs of continuing a trial. It is quite remarkable that only two patients were lost to follow-up – both more than 10 years into the study. The limitations of registry data do apply though; for example no data regarding graft function are available in the present study.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously assessed in Ekberg H, et al. ELITE-symphony study. Reduced exposure to calcineurin inhibitors in renal transplantation. New England Journal of Medicine. 2007; 357:2562
Trial registration
Not reported.