Background/Aims: Whether desensitization treatment is needed before kidney transplant (KT) in patients with high panel reactive antibody (PRA) scores but negative cross-matching (XM) tests remains controversial. This study aimed to investigate the effect of pretransplant rituximab (RTX) treatment on clinical outcomes in these patients. Methods: The study included 52 patients with PRA >50% but negative XM tests before transplantation. A single dose of RTX was administered before KT in 32 patients (RTX group). The 20 patients without RTX treatment were considered as controls (CON group). We compared the development of acute antibody-mediated rejection (AMR), rejection-free survival, allograft function, allograft and patients' survival rates and infection rates between the 2 groups. Results: The rate of acute AMR development was significantly lower in the RTX group than in the CON group (p = 0.009), and rejection-free survival in the RTX group was higher than in the CON group (p = 0.042). The 3-year graft and patient survival rates were higher in the RTX group than in the CON group (p = 0.007 and p = 0.037, respectively). There were no significant differences in infection rates between the groups. Conclusions: Pretransplant use of RTX improved the post-transplant clinical outcomes in patients with high PRAs but negative XM tests.

Keywords:
Antibody, Desensitization, Graft rejection, Kidney transplantation, Panel reactive antibody, Rituximab
1.
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.
2.
Lim WH, Chapman JR, Wong G: Peak panel reactive antibody, cancer, graft, and patient outcomes in kidney transplant recipients. Transplantation 2015;99:1043-1050.
3.
Stehlik J, Islam N, Hurst D, Kfoury AG, Movsesian MA, Fuller A, Delgado JC, Hammond ME, Gilbert EM, Renlund DG, Bader F, Fisher PW, Bull DA, Singhal AK, Eckels DD: Utility of virtual crossmatch in sensitized patients awaiting heart transplantation. J Heart Lung Transplant 2009;28:1129-1134.
4.
Kohei N, Hirai T, Omoto K, Ishida H, Tanabe K: Chronic antibody-mediated rejection is reduced by targeting B-cell immunity during an introductory period. Am J Transplant 2012;12:469-476.
5.
Kim Y, Yang CW, Moon IS, Kim M, Lim J, Park YJ, Han K, Oh EJ: Donor-specific HLA class I and CREG antibodies in complement-dependent cytotoxicity-negative renal transplants. Ann Clin Lab Sci 2010;40:330-335.
6.
Jung S, Oh EJ, Yang CW, Ahn WS, Kim Y, Park YJ, Han K: Comparative evaluation of ELISA and Luminex panel reactive antibody assays for HLA alloantibody screening. Korean J Lab Med 2009;29:473-480.
7.
Opelz G: Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 2005;365:1570-1576.
8.
Chung BH, Kim KW, Kim BM, Piao SG, Lim SW, Choi BS, Park CW, Kim YS, Cho ML, Yang CW: Dysregulation of Th17 cells during the early post-transplant period in patients under calcineurin inhibitor based immunosuppression. PLoS One 2012;7:e42011.
9.
Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M: Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008;8:753-760.
10.
Zhao YG, Shi BY, Qian YY, Bai HW, Xiao L, He XY: Clinical efficacy of rituximab for acute rejection in kidney transplantation: a meta-analysis. Int Urol Nephrol 2014;46:1225-1230.
11.
Macklin PS, Morris PJ, Knight SR: A systematic review of the use of rituximab for desensitization in renal transplantation. Transplantation 2014;98:794-805.
12.
Singh D, Kiberd BA, West KA, Kamal K, Balbontin F, Belitsky P, Lawen J: Importance of peak PRA in predicting the kidney transplant survival in highly sensitized patients. Transplant Proc 2003;35:2395-2397.
13.
Terasaki PI, Ozawa M: Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant 2004;4:438-443.
14.
Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal MM: A randomized, prospective trial of rituximab for acute rejection in pediatric renal transplantation. Am J Transplant 2008;8:2607-2617.
15.
Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC: Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 2008;359:242-251.
16.
Vo AA, Peng A, Toyoda M, Kahwaji J, Cao K, Lai CH, Reinsmoen NL, Villicana R, Jordan SC: Use of intravenous immune globulin and rituximab for desensitization of highly HLA-sensitized patients awaiting kidney transplantation. Transplantation 2010;89:1095-1102.
17.
Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki KG, Iniotaki A, Moutsopoulos HM: Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 2005;52:501-513.
18.
Scemla A, Loupy A, Candon S, Mamzer MF, Martinez F, Zuber J, Sberro R, Legendre C, Thervet E: Incidence of infectious complications in highly sensitized renal transplant recipients treated by rituximab: a case-controlled study. Transplantation 2010;90:1180-1184.
19.
Kahwaji J, Sinha A, Toyoda M, Ge S, Reinsmoen N, Cao K, Lai CH, Villicana R, Peng A, Jordan S, Vo A: Infectious complications in kidney-transplant recipients desensitized with rituximab and intravenous immunoglobulin. Clin J Am Soc Nephrol 2011;6:2894-2900.
20.
Barbosa D, Kahwaji J, Puliyanda D, Mirocha J, Reinsmoen N, Lai CH, Villicana R, Peng A, Jordan SC, Vo A, Toyoda M: Polyomavirus BK viremia in kidney transplant recipients after desensitization with IVIG and rituximab. Transplantation 2014;97:755-761.
21.
Levine MH, Abt PL: Treatment options and strategies for antibody mediated rejection after renal transplantation. Semin Immunol 2012;24:136-142.
22.
Gloor J, Stegall MD: Sensitized renal transplant recipients: current protocols and future directions. Nat Rev Nephrol 2010;6:297-306.
23.
Bayry J, Kaveri SV: Desensitization of HLA-incompatible kidney recipients. N Engl J Med 2011;365:1644; author reply 1644-1645.
24.
Vo AA, Cam V, Toyoda M, Puliyanda DP, Lukovsky M, Bunnapradist S, Peng A, Yang K, Jordan SC: Safety and adverse events profiles of intravenous gammaglobulin products used for immunomodulation: a single-center experience. Clin J Am Soc Nephrol 2006;1:844-852.
25.
Pohl MA, Lan SP, Berl T: Plasmapheresis does not increase the risk for infection in immunosuppressed patients with severe lupus nephritis. The Lupus Nephritis Collaborative Study Group. Ann Intern Med 1991;114:924-929.
26.
Chung BH, Yun JT, Ha SE, Kim JI, Moon IS, Choi BS, Park CW, Kim YS, Yang CW: Combined use of rituximab and plasmapheresis pre-transplant increases post-transplant infections in renal transplant recipients with basiliximab induction therapy. Transpl Infect Dis 2013;15:559-568.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.