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World J Nephrol. Jul 6, 2015; 4(3): 354-362
Published online Jul 6, 2015. doi: 10.5527/wjn.v4.i3.354
Modern approaches to incompatible kidney transplantation
Patarapha Wongsaroj, Joseph Kahwaji, Ashley Vo, Stanley C Jordan
Patarapha Wongsaroj, Joseph Kahwaji, Ashley Vo, Stanley C Jordan, Cedars-Sinai Medical Center, Comprehensive Transplant Center, Los Angeles, CA 90048, United States
Author contributions: Wongsaroj P and Kahwaji J contributed equally to design, data acquisition, drafting, and final approval; Vo A and Jordan SC contributed to drafting, critical revisions and final approval.
Conflict-of-interest statement: The authors do not have any competing interests in relation to the submitted work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Joseph Kahwaji, MD, MPH, Cedars-Sinai Medical Center, Comprehensive Transplant Center, 8900 Beverly Blvd, Los Angeles, CA 90048, Unites States. kahwajij@cshs.org
Telephone: +1-310-4232641 Fax: +1-310-4234678
Received: October 20, 2014
Peer-review started: October 21, 2014
First decision: November 27, 2014
Revised: March 11, 2015
Accepted: April 1, 2015
Article in press: April 7, 2015
Published online: July 6, 2015
Processing time: 258 Days and 18.8 Hours
Abstract

The presence of human-leukocyte antigen (HLA)-antibodies and blood group incompatibility remain a large barrier to kidney transplantation leading to increased morbidity and mortality on the transplant waiting list. Over the last decade a number of new approaches were developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the backbone of HLA desensitization therapy and has been shown in a prospective, randomized, placebo controlled trial to improve transplantation rates. Excellent outcomes with the addition of rituximab (anti-B cell) to IVIG based desensitization have been achieved. There is limited experience with bortezomib (anti-plasma cell) and eculizumab (complement inhibition) for desensitization. However, these agents may be good adjuncts for patients who are broadly sensitized with strong, complement-fixing HLA antibodies. Excellent short and long-term outcomes have been achieved in ABO incompatible transplantation with the combination of antibody removal, B cell depletion, and pre-transplant immunosuppression. Kidney paired donation has emerged as a reasonable alternative for programs who cannot provide desensitization or in conjunction with desensitization. Future therapies directed toward cytokines that alter B cell proliferation are under investigation.

Keywords: Desensitization; Antibodies; Intravenous immunoglobulin; Rituximab; ABO incompatible; Eculizumab; Bortezomib

Core tip: Intravenous immunoglobulin (IVIG) remains the backbone of human-leukocyte antigen (HLA) desensitization therapy and excellent outcomes with the addition of rituximab (anti-B cell) have been achieved. Bortezomib (anti-plasma cell) and eculizumab (complement inhibition) may be good adjuncts for patients who are broadly sensitized with strong, complement-fixing HLA antibodies. Excellent outcomes have been achieved in ABO incompatible transplantation with the combination of antibody removal, B cell depletion, and pre-transplant immunosuppression. Kidney paired donation has emerged as a reasonable alternative for programs who cannot provide desensitization or in conjunction with desensitization.