title: Effectiveness of the Combination of Everolimus and Tacrolimus With High Dosage of Mizoribine for Living Donor-Related Kidney Transplantation.
abstract: BACKGROUND
  Everolimus (EVR) has been used widely for the purpose of reducing the dosage of calcineurin inhibitor (CNI), leading to decreasing CNI nephrotoxicity. In Japan, high-dose mizoribine (MZR) (6 mg/kg/day) has been increasingly used because of incidences of virus infection and gastrointestinal disorder in kidney transplant recipients. However, the efficacy and safety of EVR and MZR combination therapy is still uncertain.
  
  
  METHODS
  A total of 29 living kidney transplant recipients from October 2012 to June 2014 were analyzed. Tacrolimus (TAC), MZR, basiliximab, and prednisolone were administered to all recipients. EVR was added to the regimen for 10 recipients from postoperative day 10 to 14; TAC trough levels were minimized simultaneously (EVR group). The remaining 19 recipients were defined as the control group. We evaluated the outcomes between the 2 groups.
  
  
  RESULTS
  The mean TAC trough level was 5.17 ng/mL at 1 month after transplantation in the EVR group, and 7.89 ng/mL in the control group (P = .007), respectively. The mean TAC trough level was 4.0 ng/mL at 18 months after transplantation in the EVR group, and 6.97 ng/mL in the control group (P = .003) respectively. There were no differences in the rate of acute rejection and serum creatinine level. There was no significant difference in the incidence of histological nephrotoxicity between the 2 groups in the 1-year biopsy results.
  
  
  CONCLUSIONS
  We succeeded in reducing TAC trough level immediately after transplantation by adding EVR. Our study results suggest that this combination therapy is effective for kidney transplantation recipients.
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koshino
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nobori
authors.affiliation: Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto-prefecture, Japan. Electronic address: ushi@koto.kpu-m.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Ushigome
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012263:Ribonucleosides / Q000627:therapeutic use*; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use*; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D000068338:Everolimus; D016559:Tacrolimus