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Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation

BACKGROUND. Many kidney transplant centers in the United States report both HLA class I and II antibodies detected by sensitive solid-phase assays (SPAs) to United Network for Organ Sharing as unacceptable antigens, significantly reducing the compatible donor organ pool and prolonging waiting time f...

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Autores principales: Uffing, Audrey, Hidalgo, Luis G., McMullan, Ciaran, Perry, Jacqueline, Milford, Edgar L., Murakami, Naoka, Yeung, Melissa Y., Guleria, Indira, Wood, Isabelle G., Akalin, Enver, Azzi, Jamil, Chandraker, Anil K., Riella, Leonardo V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511444/
https://www.ncbi.nlm.nih.gov/pubmed/31165081
http://dx.doi.org/10.1097/TXD.0000000000000893
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author Uffing, Audrey
Hidalgo, Luis G.
McMullan, Ciaran
Perry, Jacqueline
Milford, Edgar L.
Murakami, Naoka
Yeung, Melissa Y.
Guleria, Indira
Wood, Isabelle G.
Akalin, Enver
Azzi, Jamil
Chandraker, Anil K.
Riella, Leonardo V.
author_facet Uffing, Audrey
Hidalgo, Luis G.
McMullan, Ciaran
Perry, Jacqueline
Milford, Edgar L.
Murakami, Naoka
Yeung, Melissa Y.
Guleria, Indira
Wood, Isabelle G.
Akalin, Enver
Azzi, Jamil
Chandraker, Anil K.
Riella, Leonardo V.
author_sort Uffing, Audrey
collection PubMed
description BACKGROUND. Many kidney transplant centers in the United States report both HLA class I and II antibodies detected by sensitive solid-phase assays (SPAs) to United Network for Organ Sharing as unacceptable antigens, significantly reducing the compatible donor organ pool and prolonging waiting time for highly sensitized patients. However, the clinical relevance of all detected donor-specific antibodies (DSAs) by SPA is not unequivocal, because fluorescence intensity does not always accurately reflect antibody pathogenicity. Our center does not exclude patients from transplantation based on DSA class II. METHODS. We performed a retrospective analysis in 179 deceased-donor kidney transplant recipients with solely DSA class II before transplant and patients without DSA and compared graft survival, rejection, and clinical outcomes. Patient survival was also compared with matched controls on the waiting list. RESULTS. Patients transplanted with DSA class II showed a clear survival benefit compared with matched patients who remained on dialysis or were waitlisted on dialysis/transplanted at 5 years (100%, 34%, and 73%, respectively). After a mean follow-up of 5.5 years, there was no significant difference in death-censored graft survival between transplanted patients without DSA and those with preformed DSA class II (adjusted HR 1.10; 95% confidence interval, 0.41–2.97), although the incidence of rejection was higher in recipients with DSA class II (adjusted HR 5.84; 95% confidence interval, 2.58–13.23; P < 0.001). Serum creatinine levels at 1, 3, and 5 years posttransplant did not differ between groups. No predictors of rejection were found, although patients who received basiliximab induction therapy had higher incidence of rejection (100%) compared with those who received antithymocyte globulin (52%). CONCLUSIONS. We conclude that for highly sensitized patients, deceased-donor kidney transplantation with DSA class II yields a survival benefit over prolonged waiting time on dialysis. Instead of listing DSA class II as unacceptable antigens, an individual approach with further immunologic risk assessment is recommended.
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spelling pubmed-65114442019-06-04 Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation Uffing, Audrey Hidalgo, Luis G. McMullan, Ciaran Perry, Jacqueline Milford, Edgar L. Murakami, Naoka Yeung, Melissa Y. Guleria, Indira Wood, Isabelle G. Akalin, Enver Azzi, Jamil Chandraker, Anil K. Riella, Leonardo V. Transplant Direct Kidney Transplantation BACKGROUND. Many kidney transplant centers in the United States report both HLA class I and II antibodies detected by sensitive solid-phase assays (SPAs) to United Network for Organ Sharing as unacceptable antigens, significantly reducing the compatible donor organ pool and prolonging waiting time for highly sensitized patients. However, the clinical relevance of all detected donor-specific antibodies (DSAs) by SPA is not unequivocal, because fluorescence intensity does not always accurately reflect antibody pathogenicity. Our center does not exclude patients from transplantation based on DSA class II. METHODS. We performed a retrospective analysis in 179 deceased-donor kidney transplant recipients with solely DSA class II before transplant and patients without DSA and compared graft survival, rejection, and clinical outcomes. Patient survival was also compared with matched controls on the waiting list. RESULTS. Patients transplanted with DSA class II showed a clear survival benefit compared with matched patients who remained on dialysis or were waitlisted on dialysis/transplanted at 5 years (100%, 34%, and 73%, respectively). After a mean follow-up of 5.5 years, there was no significant difference in death-censored graft survival between transplanted patients without DSA and those with preformed DSA class II (adjusted HR 1.10; 95% confidence interval, 0.41–2.97), although the incidence of rejection was higher in recipients with DSA class II (adjusted HR 5.84; 95% confidence interval, 2.58–13.23; P < 0.001). Serum creatinine levels at 1, 3, and 5 years posttransplant did not differ between groups. No predictors of rejection were found, although patients who received basiliximab induction therapy had higher incidence of rejection (100%) compared with those who received antithymocyte globulin (52%). CONCLUSIONS. We conclude that for highly sensitized patients, deceased-donor kidney transplantation with DSA class II yields a survival benefit over prolonged waiting time on dialysis. Instead of listing DSA class II as unacceptable antigens, an individual approach with further immunologic risk assessment is recommended. Wolters Kluwer Health 2019-04-15 /pmc/articles/PMC6511444/ /pubmed/31165081 http://dx.doi.org/10.1097/TXD.0000000000000893 Text en Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. 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) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , 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.
spellingShingle Kidney Transplantation
Uffing, Audrey
Hidalgo, Luis G.
McMullan, Ciaran
Perry, Jacqueline
Milford, Edgar L.
Murakami, Naoka
Yeung, Melissa Y.
Guleria, Indira
Wood, Isabelle G.
Akalin, Enver
Azzi, Jamil
Chandraker, Anil K.
Riella, Leonardo V.
Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
title Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
title_full Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
title_fullStr Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
title_full_unstemmed Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
title_short Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
title_sort preformed donor-specific antibodies against hla class ii and graft outcomes in deceased-donor kidney transplantation
topic Kidney Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511444/
https://www.ncbi.nlm.nih.gov/pubmed/31165081
http://dx.doi.org/10.1097/TXD.0000000000000893
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