Journal List > J Korean Soc Transplant > v.32(3) > 1101757

J Korean Soc Transplant. 2018 Sep;32(3):49-56. Korean.
Published online September 27, 2018.
Copyright © the Korean Society for Transplantation, 2018
The Effect of Bortezomib on the Management of Immediate Postoperative Refractory Antibody-Mediated Rejection after Kidney Transplantation
So-Jeong Kim, M.D.,1 Kang-Woong Jun, M.D.,1 Jeong-Kye Hwang, M.D.,1 Byung-Ha Chung, M.D.,2 Chul-Woo Yang, M.D.,2 In-Sung Moon, M.D.,1 Ji-il Kim, M.D.,1 and Mi-Hyeong Kim, M.D.1
1Division of Vascular and Transplant Surgery, Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
2Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Corresponding author: Mi-Hyeong Kim. Division of Vascular and Transplant Surgery, Department of Surgery, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, 180 Wangsan-ro, Dongdaemun-gu, Seoul 02559, Korea. Tel: 82-2-961-4529, Fax: 82-2-960-4568, Email:
Received March 30, 2018; Revised June 10, 2018; Accepted July 05, 2018.



Bortezomib has been used to treat antibody-mediated rejection (AMR) that usually develops after kidney transplantation (KT). Although it has been used in various clinical situations, it is difficult to precisely define how the drug affects the clinical course. We used bortezomib to treat eight cases of AMR that developed immediately following KT in patients who were resistant to conventional treatment.


Eight cases of refractory AMR that developed immediately after KT were treated with bortezomib on days 1, 4, 8, and 11.


The resolution rate was 75%, and the 2-year rejection-free survival rate was 83%. Six cases underwent immunologically high-risk KT. Six recovering patients exhibited clinical improvement within 2 weeks of the first dose of bortezomib and recovered completely within 2 months. The effects of bortezomib seemed to be prolonged; only one additional rejection episode was observed. The two failed patients never exhibited any clinical improvement and progressed aggressively to graft failure soon after transplantation. Their donor specific anti-human leukocyte antigen antibody were sustained at high levels.


Bortezomib is an effective rescue therapy in patients with AMR that developed immediately after KT.

Keywords: Bortezomib; Graft rejection; Immunosuppression; Kidney transplantation


Fig. 1
Serum creatinine changes after bortezomib treatment of the six patients who recovered. Serum creatinine levels began to decrease within 2 weeks of bortezomib treatment, and recovery was achieved within 2 months.
Click for larger image


Table 1
Preoperative patient characteristics
Click for larger image

Table 2
Changes in donor-specific antibody levels during the peri-transplantation period
Click for larger image

Table 3
Treatments for transplant recipients exhibiting antibody-mediated rejection
Click for larger image

Table 4
Pathological features of graft biopsies of transplant recipients exhibiting antibody-mediated rejection
Click for larger image

1. Everly MJ, Everly JJ, Susskind B, Brailey P, Arend LJ, Alloway RR, et al. Bortezomib provides effective therapy for antibody-and cell-mediated acute rejection. Transplantation 2008;86:1754–1761.
2. Flechner SM, Fatica R, Askar M, Stephany BR, Poggio E, Koo A, et al. The role of proteasome inhibition with bortezomib in the treatment of antibody-mediated rejection after kidney-only or kidney-combined organ transplantation. Transplantation 2010;90:1486–1492.
3. Nigos JG, Arora S, Nath P, Hussain SM, Marcus RJ, Ko TY, et al. Treatment of antibody-mediated rejection in kidney transplant recipients: a single-center experience with a bortezomib-based regimen. Exp Clin Transplant 2012;10:609–613.
4. Hardinger KL, Alford K, Murillo D. Bortezomib as rescue therapy for antibody mediated rejection: a single-center experience. Clin Transpl 2010;24:429–436.
5. Pavlakis M. Case presentations on two patients who received bortezomib for antibody mediated rejection at BIDMC. Clin Transpl 2009;23:343–345.
6. Hardinger KL, Alford K, Murillo D. Bortezomib for acute humoral rejection in two repeat transplant recipients. Clin Transpl 2009;23:479–483.
7. Chung BH, Hong YA, Sun IO, Piao SG, Kim JI, Moon IS, et al. Determination of rituximab dose according to immunologic risk in ABO-incompatible kidney transplantation. Ren Fail 2012;34:974–979.
8. Tobian AA, Shirey RS, Montgomery RA, Tisch DJ, Ness PM, King KE. Therapeutic plasma exchange reduces ABO titers to permit ABO-incompatible renal transplantation. Transfusion 2009;49:1248–1254.
9. Walsh RC, Brailey P, Girnita A, Alloway RR, Shields AR, Wall GE, et al. Early and late acute antibody-mediated rejection differ immunologically and in response to proteasome inhibition. Transplantation 2011;91:1218–1226.
10. Kim M, Martin ST, Townsend KR, Gabardi S. Antibodymediated rejection in kidney transplantation: a review of pathophysiology, diagnosis, and treatment options. Pharmacotherapy 2014;34:733–744.
11. Roberts DM, Jiang SH, Chadban SJ. The treatment of acute antibody-mediated rejection in kidney transplant recipients: a systematic review. Transplantation 2012;94:775–783.
12. Bonomini V, Vangelista A, Frasca GM, Di Felice A, Liviano D'Arcangelo G. Effects of plasmapheresis in renal transplant rejection. A controlled study. Trans Am Soc Artif Intern Organs 1985;31:698–703.
13. Allen NH, Dyer P, Geoghegan T, Harris K, Lee HA, Slapak M. Plasma exchange in acute renal allograft rejection. A controlled trial. Transplantation 1983;35:425–428.
14. Kirubakaran MG, Disney AP, Norman J, Pugsley DJ, Mathew TH. A controlled trial of plasmapheresis in the treatment of renal allograft rejection. Transplantation 1981;32:164–165.
15. Blake P, Sutton D, Cardella CJ. Plasma exchange in acute renal transplant rejection. Prog Clin Biol Res 1990;337:249–252.
16. Sberro-Soussan R, Zuber J, Suberbielle-Boissel C, Candon S, Martinez F, Snanoudj R, et al. Bortezomib as the sole post-renal transplantation desensitization agent does not decrease donor-specific anti-HLA antibodies. Am J Transplant 2010;10:681–686.
17. Philogene MC, Sikorski P, Montgomery RA, Leffell MS, Zachary AA. Differential effect of bortezomib on HLA class I and class II antibody. Transplantation 2014;98:660–665.