Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors

A. D. Kirk*, A. Guasch, H. Xu, J. Cheeseman, S. I. Mead, A. Ghali, A. K. Mehta, D. Wu, H. Gebel, R. Bray, J. Horan, L. S. Kean, C. P. Larsen, T. C. Pearson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing regimens rely on steroids and have higher rejection rates. Experimentally, donor bone marrow and sirolimus promote belatacept's efficacy. To investigate a belatacept-based regimen without CNIs or steroids, we transplanted recipients of live donor kidneys using alemtuzumab induction, monthly belatacept and daily sirolimus. Patients were randomized 1:1 to receive unfractionated donor bone marrow. After 1 year, patients were allowed to wean from sirolimus. Patients were followed clinically and with surveillance biopsies. Twenty patients were transplanted, all successfully. Mean creatinine (estimated GFR) was 1.10 ± 0.07 mg/dL (89 ± 3.56 mL/min) and 1.13 ± 0.07 mg/dL (and 88 ± 3.48 mL/min) at 12 and 36 months, respectively. Excellent results were achieved irrespective of bone marrow infusion. Ten patients elected oral immunosuppressant weaning, seven of whom were maintained rejection-free on monotherapy belatacept. Those failing to wean were successfully maintained on belatacept-based regimens supplemented by oral immunosuppression. Seven patients declined immunosuppressant weaning and three patients were denied weaning for associated medical conditions; all remained rejection-free. Belatacept and sirolimus effectively prevent kidney allograft rejection without CNIs or steroids when used following alemtuzumab induction. Selected, immunologically low-risk patients can be maintained solely on once monthly intravenous belatacept. This study demonstrates that following alemtuzumab induction, a maintenance regimen of belatacept and sirolimus prevents rejection of live donor renal allografts and allows selected patients to be maintained rejection-free on belatacept monotherapy, eliminating the need for oral immunosuppressive therapy. (Also see brief communication by Leibler et al on page 1173.)

Original languageEnglish
Pages (from-to)1142-1151
Number of pages10
JournalAmerican Journal of Transplantation
Volume14
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

Keywords

  • Alemtuzumab
  • belatacept
  • costimulation
  • immunosuppressive regimens
  • minimization/withdrawal
  • sirolimus

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