title: Comparison between bortezomib and rituximab in the treatment of antibody-mediated renal allograft rejection.
abstract: BACKGROUND
  Antibody-mediated rejection (ABMR) following kidney transplantation is associated with poor allograft survival. Conventional treatment based on plasmapheresis (PPH) and the administration of intravenous immunoglobulins (IVIG) is not satisfactory. Two compounds, more specifically targeting B cells and plasma cells, may help to improve the prognosis: rituximab, a B-cell-depleting monoclonal antibody, and bortezomib, a proteasome inhibitor causing apoptosis of plasma cells.
  
  
  METHODS
  Starting in February 2009, we treated 10 consecutive patients with ABMR according to current Banff criteria with one cycle of bortezomib [1.3 mg/m(2) intravenously (i.v.), Day 1, 4, 8, 11]. This group was compared to a historical control group of patients (n = 9) treated with a fixed single dose of rituximab (500 mg i.v.). All patients received PPH (6×) and IVIG (30 g). Patients with acute ABMR additionally received methylprednisolone (3 × 500 mg i.v.).
  
  
  RESULTS
  Patient survival in both groups was 100%. At 18 months after treatment, graft survival was 6/10 in the bortezomib group as compared to 1/9 functioning grafts in the rituximab group (P = 0.071). Renal function was superior in patients treated with bortezomib as compared to rituximab-treated patients (serum creatinine at 9 months: 2.5 ± 0.6 versus 5.1 ± 2.1 mg/dL, P = 0.008). Proteinuria was not different between both groups (9 months: 1.3 ± 1.0 versus 1.6 ± 1.6 g/day, P = n.s.).
  
  
  CONCLUSIONS
  Treatment of ABMR with bortezomib in addition to standard therapy was partially effective, whereas treatment with a fixed dose of rituximab in addition to standard therapy with PPH and IVIG did not result in sufficient long-term graft survival. In the future, new strategies including the combination of both substances and the application of higher doses must be discussed.
authors.affiliation: Department of Nephrology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany. johannes.waiser@charite.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Waiser
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Manuela
authors.initials: M
authors.lastname: Schütz
authors.forename: Lutz
authors.initials: L
authors.lastname: Liefeldt
authors.forename: Birgit
authors.initials: B
authors.lastname: Rudolph
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D000069283:Rituximab; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001897:Boronic Acids; D016756:Immunoglobulins, Intravenous; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib