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Conversion From Calcineurin Inhibitors to Belatacept in HLA-sensitized Kidney Transplant Recipients With Low-level Donor-specific Antibodies

Ulloa, Camilo E. MD1,2,3; Anglicheau, Dany MD, PhD3; Snanoudj, Renaud MD, PhD3; Scemla, Anne MD3; Martinez, Frank MD3; Timsit, Marc-Olivier MD, PhD4; Legendre, Christophe MD, PhD3; Sberro-Soussan, Rebecca MD3

doi: 10.1097/TP.0000000000002592
Original Clinical Science–General
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Background. Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA).

Methods. We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept.

Results. Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were <1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was >3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m2 to 40.7 ± 12.3 mL/min/1.73 m2 (P < 0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection.

Conclusions. We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.

1 Nephrology Department, Clínica Alemana de Santiago – UDD, Santiago de Chile, Chile.

2 Nephrology Service, Hospital Barros Luco de Santiago de Chile, Santiago de Chile, Chile.

3 Service de Néphrologie – Transplantation rénale Adulte, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, Paris, France.

4 Service d’Urologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, Paris, France.

Received 1 May 2018. Revision received 31 October 2018.

Accepted 2 November 2018.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

The Renal Transplant Unit at Necker Hospital belongs to the Fondation Centaure and the Transplantex group, which supports a French research network on transplantation.

The authors declare no conflicts of interest.

C.E.U. participated in the acquisition, concept and design of the project, analysis and interpretation, and writing and final approval of the version to be published. R.S.-S. participated in the concept and design of the project, analysis and interpretation of the study, and final approval of the version to be published. D.A., R.S., A.S., F.M., and M.-O.T. participated in revising the study. C.L. participated in the concept, final approval of the version to be published, and revising the study.

Correspondence: Rebecca Sberro-Soussan, MD, Service de Néphrologie – Transplantation Adulte, Hôpital Necker Enfants-Malades, 149 Rue de Sèvres, 75015 Paris, France. (rebecca.sberro@aphp.fr).

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