title: Desensitization protocol in highly HLA-sensitized and ABO-incompatible high titer kidney transplantation.
abstract: BACKGROUND
  A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established.
  
  
  METHODS
  We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab.
  
  
  RESULTS
  Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients.
  
  
  CONCLUSIONS
  These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.
authors.affiliation: Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan. m9492120@msic.med.osaka-cu.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Uchida
authors.forename: Y
authors.initials: Y
authors.lastname: Machida
authors.forename: T
authors.initials: T
authors.lastname: Iwai
authors.forename: T
authors.initials: T
authors.lastname: Naganuma
authors.forename: K
authors.initials: K
authors.lastname: Kitamoto
authors.forename: T
authors.initials: T
authors.lastname: Iguchi
authors.forename: S
authors.initials: S
authors.lastname: Maeda
authors.forename: Y
authors.initials: Y
authors.lastname: Kamada
authors.forename: N
authors.initials: N
authors.lastname: Kuwabara
authors.forename: T
authors.initials: T
authors.lastname: Kim
authors.forename: T
authors.initials: T
authors.lastname: Nakatani
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D000906:Antibodies / Q000302:isolation & purification*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010956:Plasmapheresis
chemical_list: D000017:ABO Blood-Group System; D000906:Antibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D008775:Methylprednisolone