Transplant Trial Watch

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial.

Ruggenenti, P., et al.

PLoS Medicine / Public Library of Science 2021; 18(6): e1003668.

This study aimed to compare the protective effect of mycophenolate mofetil (MMF) versus Azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in renal transplant patients on steroid-free, low-dose cyclosporine immunosuppression

Patients were randomised to either the AZA group or the MMF group.

233 kidney transplant patients.

The primary outcome was biopsy-proven chronic allograft nephropathy (CAN). The secondary outcomes included the cumulative incidence of acute clinical rejections (biopsy-proven), the combined outcome of biopsy-proven clinical and subclinical rejections, graft survival, patient survival and adverse events.

47.7 (44.2 to 48.9) months median (interquartile range (IQR))

CET Conclusions
This multicentre Italian study randomized low-risk kidney transplant recipients to AZA or MMF-based immunosuppression in conjunction with cyclosporine microemulsion and basiliximab/ATG induction. Patients were followed for 4 years, with the primary endpoint being biopsy-confirmed chronic allograft nephropathy. There was no difference in CAN, patient or graft survival. There was a numerical increase in biopsy-proven acute rejection in the AZA group (29.8% vs. 16.8%), in keeping with previous studies and meta-analyses, although not meeting statistical significance probably due to lack of power. There are some issues. The study recruited patients between 2007 and 2012, when cyclosporine was still in widespread use. Most centres have now switched to tacrolimus-based immunosuppression, and it is not clear why this study has taken 9 years to reach publication. Less than half of participants had the protocol surveillance biopsy, meaning that the primary endpoint was based on for-cause biopsies at varying timepoints in a large proportion of patients. Around 1/3 patients switched from AZA to MMF during the course of the study. Overall, the findings here are unlikely to challenge the idea that Tac/MMF-based immunosuppression is gold-standard for most patients, but do provide a reminder that AZA offers a useful alternative in resource-constrained environments or patients unable to tolerate MMF.

Jadad score

Data analysis
Modified intention-to-treat analysis

Allocation concealment

Trial registration - NCT00494741; EUDRACT 2006-005604-14.

Funding source
Non-industry funded