title: Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors.
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.
authors.affiliation: Emory Transplant Center, Emory University, Atlanta, GA.
authors.forename: A D
authors.initials: AD
authors.lastname: Kirk
authors.forename: A
authors.initials: A
authors.lastname: Guasch
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Cheeseman
authors.forename: S I
authors.initials: SI
authors.lastname: Mead
authors.forename: A
authors.initials: A
authors.lastname: Ghali
authors.forename: A K
authors.initials: AK
authors.lastname: Mehta
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Gebel
authors.forename: R
authors.initials: R
authors.lastname: Bray
authors.forename: J
authors.initials: J
authors.lastname: Horan
authors.forename: L S
authors.initials: LS
authors.lastname: Kean
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
authors.forename: T C
authors.initials: TC
authors.lastname: Pearson
mesh_terms: D000069594:Abatacept; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D019468:Disease Management; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control; D011379:Prognosis; D020123:Sirolimus / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D020123:Sirolimus
keywords: Alemtuzumab; belatacept; costimulation; immunosuppressive regimens; minimization/withdrawal; sirolimus