title: Treatment of Acute Antibody-Mediated Renal Allograft Rejection With Cyclophosphamide.
abstract: Antibody-mediated rejection (AMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated whether cyclophosphamide combined with plasmapheresis and intravenous immunoglobulins is an option for patients with AMR.
  
  
  
  Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute AMR with intravenous cyclophosphamide pulses (15 mg/kg adapted to age and renal function) at 3-week intervals, PPH (6×), and high-dose intravenous immunoglobulin (1.5 g/kg). Treatment was completed after 6 cyclophosphamide pulses or in case of return to baseline serum creatinine together with reduction of donor-specific HLA antibodies (DSA) below 500 mean fluorescence intensity.
  
  
  
  Eleven of 13 patients completed treatment. Median follow-up was 18 (12-44) months. At the end of follow-up, graft survival was 77% (10/13). The 3 graft losses were caused at least in part by nonadherence and premature termination of treatment. Serum creatinine increased from 1.7±0.4 mg/dL at 3 months before diagnosis to 3.7±2.4 mg/dL at diagnosis (P = 0.01), and decreased to 2.1 ± 0.7 mg/dL at 3 months after diagnosis (P = 0.01). In 7 (64%) of 11 patients, who completed treatment, DSA decreased, in 4 (36%) of 11 DSA were below 500 mean fluorescence intensity after treatment. Dose reductions had to be performed in 3 of 13 patients for leukopenia. We observed 14 hospitalizations in 9 of 13 patients.
  
  
  
  To our knowledge, this is the first systematic report on cyclophosphamide-based treatment of acute AMR based on modern diagnostics. Treatment was effective and relatively safe. Future studies will show, whether cyclophosphamide proves to be a valuable alternative for the treatment of AMR.
authors.affiliation: 1 Medizinische Klinik mit Schwerpunkt Nephrologie, Charité Universitätsmedizin Berlin, Berlin, Germany. 2 Institut für Pathologie, Charité Universitätsmedizin Berlin, Berlin, Germany. 3 HLA-Labor, Zentrum für Tumormedizin, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Waiser
authors.forename: Michael
authors.initials: M
authors.lastname: Duerr
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
authors.forename: Birgit
authors.initials: B
authors.lastname: Rudolph
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Wu
authors.forename: Friederike
authors.initials: F
authors.lastname: Bachmann
authors.forename: Fabian
authors.initials: F
authors.lastname: Halleck
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
mesh_terms: D000208:Acute Disease; D000328:Adult; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007275:Injections, Intravenous; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D003520:Cyclophosphamide