Transplant Trial Watch

Distinct peripheral blood molecular signature emerges with successful tacrolimus withdrawal in kidney transplant recipients.

Cravedi, P., et al.

American Journal of Transplantation 2020 [record in progress].

The aim of this study was to perform a microarray analyses of peripheral blood mononuclear cells (PBMC) RNA from kidney transplant patients that were enrolled in the Clinical Trials in Organ Transplantation-09 (CTOT-09) trial.

Participants were randomized to Tac withdrawal or continuation, in addition to receiving mycophenolate mofetil (MMF) and prednisone.

21 kidney transplant recipients.

The main outcomes of interest included PBMC transcriptional profiles, and phenotypic and functional analyses of peripheral T cells.

9 months

CET Conclusions
This is a very interesting study of tacrolimus withdrawal following renal transplantation. This particular paper focusses on RNA analyses and flow cytometry of PBMCs comparing patients with successful tacrolimus withdrawal and those that experience acute rejection or rise in DSA. Fourteen patients were randomised to tacrolimus withdrawal and 7 remained on tacrolimus. The study had was stopped early due to the high risk of acute rejection or de novo DSA (8/14), as described in the paper by Hricik et al. Six patients remained off tacrolimus for 24 months with stable function and without acute rejection or DSA. The microarray analysis showed a clear differential in expression of genes between those that would successfully complete tacrolimus and those that would not. Anti-donor reactivity was assessed by IFN-gamma ELISPOT and at 6 months after transplant, prior to tacrolimus withdrawal, the responses in all patients who successfully stopped tacrolimus were below the threshold of positivity. Whilst the study shows that untargeted withdrawal of tacrolimus is inadvisable, it may be possible to target immune suppression reduction in the future using some of the predictors of success described in this paper.

Trial registration - NCT01517984

Funding source
Non-industry funded