title: Partial therapeutic response to Rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. rnsmith@partners.org
authors.forename: R Neal
authors.initials: RN
authors.lastname: Smith
authors.forename: Fahim
authors.initials: F
authors.lastname: Malik
authors.forename: Nelson
authors.initials: N
authors.lastname: Goes
authors.forename: Alton B
authors.initials: AB
authors.lastname: Farris
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Zorn
authors.forename: Susan
authors.initials: S
authors.lastname: Saidman
authors.forename: Nina
authors.initials: N
authors.lastname: Tolkoff-Rubin
authors.forename: Sonika
authors.initials: S
authors.lastname: Puri
authors.forename: Waichi
authors.initials: W
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D054316:Biomarkers, Pharmacological / Q000097:blood; D002648:Child; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000276:immunology; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003404:Creatinine