title: Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.
abstract: Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.
authors: From the Department of Nephrology, Ajou University School of Medicine, Suwon (JCJ); Transplantation Research Institute, Seoul National University Hospital, Seoul (EJ, CA, JY); Department of Internal Medicine, BHS-Han Seo Hospital, Pusan (HYK); Department of Internal Medicine, Division of Nephrology, Korea University Anam Hospital (M-GK); Transplantation Center, Seoul National University Hospital (HJI, TYK, CA, JY); Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital (HJJ); Department of Laboratory Medicine, Seoul National University College of Medicine (JWI, EYS); Department of Internal Medicine (MH, CA); and Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, South Korea (JC).
authors: Jong Cheol
authors: JC
authors: Jeong
authors: Enkthuya
authors: E
authors: Jambaldorj
authors: Hyuk Yong
authors: HY
authors: Kwon
authors: Myung-Gyu
authors: MG
authors: Kim
authors: Hye Jin
authors: HJ
authors: Im
authors: Hee Jung
authors: HJ
authors: Jeon
authors: Ji Won
authors: JW
authors: In
authors: Miyeun
authors: M
authors: Han
authors: Tai Yeon
authors: TY
authors: Koo
authors: Junho
authors: J
authors: Chung
authors: Eun Young
authors: EY
authors: Song
authors: Curie
authors: C
authors: Ahn
authors: Jaeseok
authors: J
authors: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D000069286:Bortezomib / Q000008:administration & dosage*; D003888:Desensitization, Immunologic / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000601:surgery; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011300:Preoperative Care / Q000379:methods; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000069283:Rituximab / Q000008:administration & dosage; D016896:Treatment Outcome; D014850:Waiting Lists
chemical_list: D000970:Antineoplastic Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab; D000069286:Bortezomib