TY - JOUR
T1 - Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation
AU - Uffing, Audrey
AU - Hidalgo, Luis G.
AU - McMullan, Ciaran
AU - Perry, Jacqueline
AU - Milford, Edgar L.
AU - Murakami, Naoka
AU - Yeung, Melissa Y.
AU - Guleria, Indira
AU - Wood, Isabelle G.
AU - Akalin, Enver
AU - Azzi, Jamil
AU - Chandraker, Anil K.
AU - Riella, Leonardo V.
N1 - Funding Information:
This work was conducted with the support from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic healthcare centers. This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. Correspondence: Dr Leonardo V. Riella, 221 Longwood Avenue, Boston, MA 02115. (lriella@bwh.harvard.edu). 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), 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.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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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U2 - 10.1097/TXD.0000000000000893
DO - 10.1097/TXD.0000000000000893
M3 - Article
AN - SCOPUS:85082562821
SN - 2373-8731
VL - 5
JO - Transplantation Direct
JF - Transplantation Direct
IS - 5
M1 - e446
ER -