title: Usefulness and safety of high-dose mizoribine on ABO-incompatible living related kidney transplantation using anti-CD20 and anti-CD25 antibodies without splenectomy: 3-year results.
abstract: BACKGROUND
  Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years.
  
  
  METHODS
  From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) .
  
  
  RESULTS
  The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups.
  
  
  CONCLUSIONS
  A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Organ Interaction Research Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: nyoshi@koto.kpu-m.ac.jp.
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ushigome
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nobori
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Organ Interaction Research Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koshino
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ito
mesh_terms: D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D016030:Kidney Transplantation; D012263:Ribonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013156:Splenectomy
chemical_list: D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D012263:Ribonucleosides; C010052:mizoribine; D003404:Creatinine