Background. The clinical impact of weakly reactive pretransplant donor-specific antibody (DSA) in kidney transplantation is controversial. While some evidence suggests that weakly reactive DSA can lead to rejection, it is unclear which patients are at risk for rejection and whether posttransplant changes in weakly reactive DSA are clinically meaningful. Methods. We retrospectively studied 80 kidney transplant recipients with weakly reactive pretransplant DSA between 2007 and 2014. We performed a multivariate Cox regression analysis to identify immunologic factors most associated with risk of biopsy-proven rejection. Results. Biopsy-proven rejection occurred in 13 of 80 (16%) patients. The presence of both class I and II DSA before transplant (hazards ratio 17.4, P < 0.01) and any posttransplant increase in DSA reactivity above a mean fluorescence intensity of 3000 (hazards ratio 7.8, P < 0.01) were each significantly associated with an increased risk of rejection, which primarily occurred within the first 18 months. Conclusions. Pretransplant DSA class and DSA kinetics after transplantation are useful prognostic indicators in patients with weak DSA reactivity. These results identify a small, high-risk patient group that warrants aggressive posttransplant DSA monitoring and may benefit from alternative donor selection.
|State||Published - Aug 1 2019|
Bibliographical noteFunding Information:
Received 31 May 2019. Accepted 19 June 2019. 1Department of Surgery, University of Pennsylvania, Philadelphia, PA. 2Department of Surgery, Transplant Center, University of Kentucky College of Medicine, Lexington, KY. 3Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA. 4Department of Pathology, University of Pennsylvania, Philadelphia, PA. A.H.M. and M.G. contributed equally to this work. A.H.M., M.G., D.S., M.K., and P.M.P. designed the research project. A.H.M., M.A.L., K.L., J.T.C., and M.H.L. acquired the data. A.H.M. and M.G. performed the data analysis. A.H.M., M.G., and P.M.P. wrote the manuscript. All authors contributed to the revision and approval of the manuscript. M.K. serves on the Advisory Scientific Board of Omixon Inc. M.H.L. receives study drug from Pfizer, Inc. The institution has received research funding from Veloxis Pharmaceuticals Inc.
A.H.M. was supported in part by the University of Pennsylvania Agnew Summer Scholars Research Program. Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantationdirectjournal.com) Correspondence: Paige M. Porrett, MD, PhD, Department of Surgery, University of Pennsylvania, 3400 Spruce Street, 2 Dulles Courtyard, Philadelphia, PA 19104. (email@example.com). 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.
© 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
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