title: Bortezomib for the treatment of chronic antibody-mediated kidney allograft rejection: a case report.
abstract: We report on a patient with chronic C4d-positive antibody-mediated rejection, who was subjected to treatment with bortezomib. Despite initial treatment with CD20 antibody rituximab and intravenous immunoglobulin, the patient presented with a steady increase in serum creatinine and de novo proteinuria. In an effort to directly target alloantibody-producing plasma cells and to prevent ongoing antibody-mediated graft injury, we applied treatment with a single cycle of bortezomib combined with dexamethasone. Treatment was associated with a > 50% decrease in DSA levels and disappearance of capillary C4d staining as detected in a follow-up biopsy. However, there were still profound glomerulitis, an unchanged degree of transplant glomerulopathy and a persistent discrete infiltration of the interstitium by CD138+ plasma cells. The clinical course was unfavorable: despite some decrease in urinary protein excretion, a further deterioration of kidney allograft function was noted. In summary, this case suggests distinct antihumoral efficacy of bortezomib also in the context of chronic AMR. Nevertheless, a major observation was that treatment failed to prevent deterioration of graft function. We speculate that, despite modulation of (complement-activating) DSA, advanced irreversible tissue injury in this late stage of rejection may have precluded a relevant clinical response. Together with other case studies, our results may provide a valuable basis for prospective trials designed to evaluate the efficacy of bortezomib in the prevention and treatment of earlier stages of chronic AMR, e.g. based on the results of early (protocol) biopsies and/or early post-transplant antibody monitoring.
authors.affiliation: Division of Nephrology and Dialysis, Department of Medicine ll, Medical University Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwaiger
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Werzowa
authors.forename: Bettina
authors.initials: B
authors.lastname: Haidbauer
authors.forename: Alice
authors.initials: A
authors.lastname: Schmidt
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D001706:Biopsy; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002908:Chronic Disease; D015935:Complement C4b / Q000276:immunology; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D015935:Complement C4b; C032261:complement C4d; D046988:Proteasome Endopeptidase Complex