Azathioprine as good as Mycophenolate mofetil for immunosuppression after kidney transplant: Study

A group of researchers from U.S.A and Italy conducted a study to evaluate the efficacy of mycophenolate mofetil (MMF) and azathioprine (AZA) against acute cellular rejection (ACR) and chronic allograft nephropathy (CAN) in kidney transplant recipients on steroid-free, low-dose cyclosporine microemulsion maintenance immunosuppression.

The researchers conducted a pragmatic, prospective, multicentre trial conducted in 6 Italian transplant centers, between June 2007 and July 2012 and followed up to August 2016. They compared the outcomes of 233 kidney transplant recipients of a first deceased donor kidney transplant induced with low-dose thymoglobulin and basiliximab and randomized to mycophenolate mofetil (MMF) (750 mg twice/day, n = 119) or azathioprine (AZA) (75 to 125 mg/day, n = 114) with low-dose cyclosporine microemulsion and 1-week steroid. The low-dose cyclosporine dosage was halved in patients without acute clinical or subclinical rejections. Primary endpoint was biopsy-proven chronic allograft nephropathy.

The findings of the study are as follows:

· The donor/recipient mismatches and follow-up low dose cyclosporine blood levels were similar between group donor and recipient characteristics.

· Approximately same percentage of biopsied patients treated by either Azathioprine (35.2%) or Mycophenolate mofetil (33.3%) developed chronic allograft nephropathy (hazard ratio (HR) [95% confidence interval (CI)]: 1.147 (0.691 to 1.904, p = 0.595).

· 20 and 21 patients on Mycophenolate mofetil as compared to 34 and 14 on Azathioprine showed either clinical or biopsy-proven subclinical acute cellular rejection, respectively.

· There were no significant differences in combined events of patient and graft survival, delayed graft function (DGF), 3-year glomerular filtration rate, and any adverse events in both groups.

The authors concluded that in the donor kidney transplant recipients who died and were on low-dose cyclosporine and no steroids, Mycophenolate mofetil showed no superior benefit as compared to Azathioprine. Thus, as Azathioprine is cheaper than Mycophenolate mofetil, Azathioprine can be safely used as an alternative to Mycophenolate mofetil, in combination with minimized immunosuppression.

Reference:

Mycophenolate mofetil versus azathioprine in kidney transplant recipients on steroid-free, low-dose cyclosporine immunosuppression (ATHENA): A pragmatic randomized trial by Ruggenenti P et. al published in the Plos One journal.

https://doi.org/10.1371/journal.pmed.1003668