Late antibody-mediated rejection in renal allografts: outcome after conventional and novel therapies. 2014

Gaurav Gupta, and Bassam G Abu Jawdeh, and Lorraine C Racusen, and Bhavna Bhasin, and Lois J Arend, and Brandon Trollinger, and Edward Kraus, and Hamid Rabb, and Andrea A Zachary, and Robert A Montgomery, and Nada Alachkar
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.

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.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007518 Isoantibodies Antibodies from an individual that react with ISOANTIGENS of another individual of the same species. Alloantibodies
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010956 Plasmapheresis Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. Double Filtration Plasmapheresis,Therapeutic Immunoadsorption,Therapeutic Plasma Adsorption,Therapeutic Plasmapheresis,Adsorption, Therapeutic Plasma,Adsorptions, Therapeutic Plasma,Double Filtration Plasmaphereses,Filtration Plasmapheresis, Double,Immunoadsorption, Therapeutic,Plasma Adsorption, Therapeutic,Plasmaphereses,Plasmapheresis, Double Filtration,Plasmapheresis, Therapeutic,Therapeutic Immunoadsorptions,Therapeutic Plasma Adsorptions,Therapeutic Plasmaphereses
D011719 Pyrazines A heterocyclic aromatic organic compound with the chemical formula C4H4N2. Pyrazine
D001897 Boronic Acids Inorganic or organic compounds that contain the basic structure RB(OH)2. Boronic Acid,Acid, Boronic,Acids, Boronic
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D005260 Female Females
D006084 Graft Rejection An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. Transplant Rejection,Rejection, Transplant,Transplantation Rejection,Graft Rejections,Rejection, Graft,Rejection, Transplantation,Rejections, Graft,Rejections, Transplant,Rejections, Transplantation,Transplant Rejections,Transplantation Rejections

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