25. High tacrolimus intra-patient variability is associated with elevated anti-donor reactivity after kidney transplantation

A. Mendoza Rojas, P. de Kuiper, D. Reijerkerk, M.L. Mccahery, M.C. Clahsen-van Groningen, T. van Gelder, D.A. Hesselink, C.C. Baan, N.M. van Besouw

Thursday 5 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 6 – Basale abstracts

Background: High numbers of donor-reactive, IFN-γ producing peripheral blood mononuclear cells (PBMCs) prior to transplantation have been associated with acute rejection. Additionally, a high tacrolimus (Tac) intra-patient variability (IPV) has previously been associated with higher rejection rates. Currently, knowledge about the effect of a high IPV on donor-reactive IFN-γ producing cells is unknown. In this present study, our aim is i. to validate whether donor-reactive, IFN-γ producing cells are associated with rejection and ii. to asses if their frequency is affected by Tac IPV after kidney transplantation.

Methods: PBMC samples from 78 kidney transplant patients were obtained at pre-transplantation, at 1 year and 5-7 years after transplantation. The frequency of IFN-γ producing PBMCs was determined by Elispot. Patient PBMCs were stimulated with irradiated donor or completely HLA mismatched third-party cells. Tac IPV was calculated between 6 to 12 months after transplantation of at least 3 pre-dose Tac concentrations corrected for the corresponding daily Tac dose.

Results: The number of donor-reactive, IFN-γ producing cells prior to transplantation was associated with rejection episodes after transplantation [median and interquartile range: no rejection 20/1x105 PBMC (7-48) vs rejection 42/1x105 PBMC (23-72), p=0.018], while third party reactivity was comparable between patients with and without rejections. Approximately 22% of patients had a high Tac IPV of 30% or more. Tac IPV was positively correlated with high numbers of donor-reactive IFN-γ producing cells 1 year after transplantation (r=0.30; p=0.02).

Conclusions: Patients with high variability in Tac pre-dose concentrations are at risk for high numbers of donor-reactive T cells at 1 year after transplantation. These patients should be carefully monitored to prevent rejection.