A search for a biomarker to predict belatacept-resistant rejection in kidney transplantation

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G.N. de Graav, C.C. Baan, M.C. Clahsen-van Groningen, R. Kraaijeveld, M. Dieterich, W. Verschoor, D.L. Roelen, M. Cadogan, J. van de Wetering, J. van Rosmalen, W. Weimar, D.A. Hesselink

Chair(s): dr. D.A. Hesselink

Thursday 9 march 2017

12:30 - 12:45h

Categories: Poster - Klinisch

Parallel session: Postersessie - Klinisch 1

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Belatacept, an inhibitor of the CD28-CD80/86 co-stimulatory pathway, allows for calcineurin-inhibitor free immunosuppressive therapy in kidney transplantation but has been associated with a higher acute rejection risk than ciclosporin. Thus far, no biomarker for belatacept-resistant rejection has been identified.

In this randomized controlled trial, 40 kidney transplant recipients were 1:1 randomized to belatacept or tacrolimus combined with basiliximab, mycophenolate mofetil and prednisolone. The 1-year incidence of biopsy-proven acute rejection (BPAR) was monitored. Potential biomarkers, namely CD8⁺CD28^-, CD4⁺CD57⁺PD1^- and CD8⁺CD28⁺⁺ EMRA T-cells were measured pre-transplantation and correlated to BPAR after transplantation. Pharmacodynamic monitoring of belatacept was performed by measuring free CD86 on circulating monocytes.

The incidence of BPAR was higher among belatacept-treated than tacrolimus-treated patients: 50% vs. 10%; p = 0.01. The majority of rejections occurred within 3 months after transplantation. Three graft losses, due to BPAR, occurred in the belatacept group vs. none in the tacrolimus group. There were no differences in pre-transplant values of the biomarkers between rejectors and non-rejectors in the belatacept group. In univariable Cox regression analyses, the studied cell subsets were not significantly associated with the risk of developing BPAR. CD86 molecules on circulating monocytes in belatacept-treated patients were saturated at all time points.

Belatacept-based immunosuppressive therapy resulted in significantly higher and more severe acute rejection compared to standard, tacrolimus-based therapy. Neither cellular biomarkers nor insufficient blockade of the CD28-CD80/86 co-stimulatory pathway predicted BPAR.