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      Successful Simultaneous Liver-Kidney Transplantation in the Presence of Multiple High-Titered Class I and II Antidonor HLA Antibodies

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          Abstract

          The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents. The kidney transplant was delayed by 6 hours after the liver transplant to allow more time to the liver allograft to “absorb” donor-specific antibodies (DSA). Interestingly, the liver allograft did not prevent immediate antibody-mediated injury to the kidney allograft in this highly sensitized recipient. Anti-HLA single antigen bead analysis of liver and kidney allograft biopsy eluates revealed deposition of both class I and II DSA in both liver and kidney transplants during the first 2 weeks after transplant. Afterward, both liver and kidney allograft functions improved and remained normal after a year with progressive reduction in serum DSA values.

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          The new liver allocation system: moving toward evidence-based transplantation policy.

          Robert Lake, J Turcotte, Lewis Teperman … (2002)
          In 1999, the Institute of Medicine suggested that instituting a continuous disease severity score that de-emphasizes waiting time could improve the allocation of cadaveric livers for transplantation. This report describes the development and initial implementation of this new plan. The goal was to develop a continuous disease severity scale that uses objective, readily available variables to predict mortality risk in patients with end-stage liver disease and reduce the emphasis on waiting time. Mechanisms were also developed for inclusion of good transplant candidates who do not have high risk of death but for whom transplantation may be urgent. The Model for End-Stage Liver Disease (MELD) and Pediatric End-Stage Liver Disease (PELD) scores were selected as the basis for the new allocation policy because of their high degree of accuracy for predicting death in patients having a variety of liver disease etiologies and across a broad spectrum of liver disease severity. Except for the most urgent patients, all patients will be ranked continuously under the new policy by their MELD/PELD score. Waiting time is used only to prioritize patients with identical MELD/PELD scores. Patients who are not well served by the MELD/PELD scores can be prioritized through a regionalized peer review system. This new liver allocation plan is based on more objective, verifiable measures of disease severity with minimal emphasis on waiting time. Application of such risk models provides an evidenced-based approach on which to base further refinements and improve the model.
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            Prospective iterative trial of proteasome inhibitor-based desensitization.

            E S Woodle, A R Shields, N Ejaz … (2015)
            A prospective iterative trial of proteasome inhibitor (PI)-based therapy for reducing HLA antibody (Ab) levels was conducted in five phases differing in bortezomib dosing density and plasmapheresis timing. Phases included 1 or 2 bortezomib cycles (1.3 mg/m(2) × 6-8 doses), one rituximab dose and plasmapheresis. HLA Abs were measured by solid phase and flow cytometry (FCM) assays. Immunodominant Ab (iAb) was defined as highest HLA Ab level. Forty-four patients received 52 desensitization courses (7 patients enrolled in multiple phases): Phase 1 (n = 20), Phase 2 (n = 12), Phase 3 (n = 10), Phase 4 (n = 5), Phase 5 (n = 5). iAb reductions were observed in 38 of 44 (86%) patients and persisted up to 10 months. In Phase 1, a 51.5% iAb reduction was observed at 28 days with bortezomib alone. iAb reductions increased with higher bortezomib dosing densities and included class I, II, and public antigens (HLA DRβ3, HLA DRβ4 and HLA DRβ5). FCM median channel shifts decreased in 11/11 (100%) patients by a mean of 103 ± 54 mean channel shifts (log scale). Nineteen out of 44 patients (43.2%) were transplanted with low acute rejection rates (18.8%) and de novo DSA formation (12.5%). In conclusion, PI-based desensitization consistently and durably reduces HLA Ab levels providing an alternative to intravenous immune globulin-based desensitization.
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              Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database.

              Tse-Ling Fong, J Cicciarelli, Ken Cho … (2006)
              There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. Renal half-life of KALT allografts was shorter than CLKT group (6.6+/-0.9 vs. 11.7+/-1.3 years, P < 0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P < 0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P < 0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P < 0.001). Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transplant Direct
                Journal ID (iso-abbrev): Transplant Direct
                Journal ID (publisher-id): TXD
                Title: Transplantation Direct
                Publisher: Lippincott Williams & Wilkins
                ISSN (Electronic): 2373-8731
                Publication date Collection: December 2016
                Publication date (Electronic): 23 November 2016
                Volume: 2
                Issue: 12
                Electronic Location Identifier: e121
                Affiliations
                Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH.
                Author notes
                Correspondence: Flavio Paterno, MD, Division of Transplant Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0519, MSB 2006A, Cincinnati, OH 45267-0558. ( flavio.paterno@ 123456uc.edu ).
                Article
                Publisher ID: TXD50111 Accession ID: 00008
                DOI: 10.1097/TXD.0000000000000633
                PMC ID: 5142368
                PubMed ID: 27990486
                SO-VID: fffd30d7-4683-4128-a7c7-c0d017e8293b
                Copyright © Copyright © 2016 The Authors. Transplantation Direct. Published by Wolters Kluwer Health, Inc.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                Date received : 23 August 2016
                Date revision requested : 26 September 2016
                Date accepted : 28 September 2016
                Page count
                Pages: 0
                Categories
                Subject: Case Study Reports
                Custom metadata
                OPEN-ACCESS TRUE

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