title: Late antibody-mediated rejection in renal allografts: outcome after conventional and novel therapies.
abstract: BACKGROUND
  Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR.
  
  
  METHODS
  Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength.
  
  
  RESULTS
  Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06).
  
  
  CONCLUSIONS
  A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.
authors.affiliation: 1 Department of Medicine, Virginia Commonwealth University, Richmond, VA. 2 Department of Medicine, University of Cincinnati, Cincinnati, OH. 3 Department of Pathology, Johns Hopkins University, Baltimore, MD. 4 Department of Medicine, Johns Hopkins University, Baltimore, MD. 5 Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD. 6 Department of Surgery, Johns Hopkins University, Baltimore, MD. 7 Address correspondence to: Nada Alachkar, MD, Johns Hopkins University School of Medicine, 600 Wolfe Street, Brady 502, Baltimore, MD 21287.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Gupta
authors.forename: Bassam G
authors.initials: BG
authors.lastname: Abu Jawdeh
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Racusen
authors.forename: Bhavna
authors.initials: B
authors.lastname: Bhasin
authors.forename: Lois J
authors.initials: LJ
authors.lastname: Arend
authors.forename: Brandon
authors.initials: B
authors.lastname: Trollinger
authors.forename: Edward
authors.initials: E
authors.lastname: Kraus
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
authors.forename: Robert A
authors.initials: RA
authors.lastname: Montgomery
authors.forename: Nada
authors.initials: N
authors.lastname: Alachkar
mesh_terms: D000328:Adult; D064591:Allografts; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D003404:Creatinine / Q000097:blood; D057915:Drug Substitution; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006085:Graft Survival; D006801:Humans; D056724:Immunity, Humoral; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010956:Plasmapheresis; D011719:Pyrazines / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015415:Biomarkers; D001897:Boronic Acids; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D003404:Creatinine