Desensitization using bortezomib and high-dose immunoglobulin increases rate of deceased donor kidney transplantation

Jong Cheol Jeong, Enkthuya Jambaldorj, Hyuk Yong Kwon, Myung Gyu Kim, Hye Jin Im, Hee Jung Jeon, Ji Won In, Miyeun Han, Tai Yeon Koo, Junho Chung, Eun Young Song, Curie Ahn, Jaeseok Yang

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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/m2), and 4 doses of bortezomib (1.3 mg/m2). 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; P1/40.004). 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, highdose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

Original languageEnglish
Article numbere2635
JournalMedicine (United States)
Volume95
Issue number5
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Medicine(all)

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    Jeong, J. C., Jambaldorj, E., Kwon, H. Y., Kim, M. G., Im, H. J., Jeon, H. J., In, J. W., Han, M., Koo, T. Y., Chung, J., Song, E. Y., Ahn, C., & Yang, J. (2016). Desensitization using bortezomib and high-dose immunoglobulin increases rate of deceased donor kidney transplantation. Medicine (United States), 95(5), [e2635]. https://doi.org/10.1097/MD.0000000000002635