title: Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation.
abstract: BACKGROUND
  Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy.
  
  
  METHODS
  Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m2at day -14 and day -1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant.
  
  
  RESULTS
  Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year.
  
  
  CONCLUSIONS
  Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).
authors.affiliation: Niigata Organ Transplant Foundation, Niigata, Japan. takahashi-kouta@image.ocn.ne.jp.|, 1-23-3 Kitaotsuka, Toshima-ku, Tokyo, 170-0004, Japan. takahashi-kouta@image.ocn.ne.jp.
authors.forename: Kota
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.affiliation: Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Fuchinoue
authors.affiliation: Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, Tochigi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yagisawa
authors.affiliation: Department of Nephrology, Toho University, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Aikawa
authors.affiliation: Transplant Surgery, Nagoya Daini Red Cross Hospital, Aichi, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Watarai
authors.affiliation: Department of Organ Transplant and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Nephrology, Masuko Memorial Hospital, Aichi, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Morozumi
authors.affiliation: Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001787:Blood Group Incompatibility / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007518:Isoantibodies / Q000276:immunology; D007564:Japan; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000017:ABO Blood-Group System; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab
keywords: ABO incompatibility; Antibody-mediated rejection; Desensitization therapy; Kidney transplantation; Plasma exchange; Rituximab