Partial therapeutic response to Rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts

• Type of Material: Article
• Authors: R. Neal Smith, Harvard University; Fahim Malik, Harvard University; Nelson Goes, Swedish Medical Center; Alton B Farris III, Emory University; Emmanuel Zorn, Harvard University; Susan Saidman, Harvard University; Nina Tolkoff-Rubin, Harvard University; Sonika Puri, Harvard University; Waichi Wong, Harvard University
• Language: English
• Date: 2012-10-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.trim.2012.08.005
• Title of Journal or Parent Work: Transplant Immunology
• ISSN: 0966-3274
• Volume: 27
• Issue: 0
• Start Page: 107
• End Page: 113
• Keywords: HUMORAL REJECTION; Donor specific antibodies; Immunology; MEMBRANOUS GLOMERULONEPHRITIS; Transplantation; C4D DEPOSITS; HLA ANTIBODIES; Life Sciences & Biomedicine; TRANSPLANT GLOMERULOPATHY; IN-VIVO; ANTI-CD20 MONOCLONAL-ANTIBODY; Renal allograft survival; PERITUBULAR CAPILLARIES; Science & Technology; Rituximab; RENAL-ALLOGRAFTS; Chronic humoral rejection; ANTIGEN-PRESENTING CELLS
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

Background and Objectives: Chronic rejection leads to kidney allograft failure and develops in many kidney transplant recipients. One cause of chronic rejection, chronic antibody mediated rejection (CAMR), is attributed to alloantibodies. Maintenance immunosuppression including prednisone, mycophenolate mofetil (MMF) and calcineurin inhibitors may limit alloantibody production in some patients, but many maintain or develop alloantibody production, leading to CAMR. Therefore, no efficacious therapy to treat CAMR is presently available to prevent the progression of CAMR to kidney allograft failure. Design, Setting, Participants, and Measurements: We performed a retrospective review of 31 subjects with CAMR, of which 14 received Rituximab and 17 subjects did not. Response to Rituximab was defined as decline or stabilization of serum creatinine for at least one year. Data reviewed included demographic, clinical, allograft, post-transplant, and pathological variables. Pathological variables in the diagnostic allograft biopsy were scored according to Banff criteria. Results: The median survival time (MST) for allografts in the control group was 439. days, and for the Rituximab treated group was 685. days. The Rituximab group was dichotomous with 8 subjects showing a medial survival time of 1180. days, and 6 subjects having a median survival time of 431. days. The MST for the responders was statistically significant from the non-responders and controls. No pathological parameter distinguished any subset of subjects. Conclusions: These data show that Rituximab followed by standard maintenance immunosuppression shows a therapeutic effect in the treatment of CAMR, which is confined to a subset of treated subjects, not identifiable a priori.