Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

Detection of Complement-binding Donor-specific Antibodies, Not IgG-antibody Strength Nor C4d Status, at Antibody-mediated Rejection Diagnosis Is an Independent Predictor of Kidney Graft Failure

Malheiro, Jorge, MD1,2; Santos, Sofia, MD1; Tafulo, Sandra, MSc3; Dias, Leonídio, MD1; Martins, La Salete, MD, PhD1,2; Fonseca, Isabel, MSc, PhD1,2; Almeida, Manuela, MD1,2; Pedroso, Sofia, MD1; Beirão, Idalina, MD, PhD1,2; Castro-Henriques, António, MD1,2; Cabrita, António, MD1

doi: 10.1097/TP.0000000000002265
Original Clinical Science—General

Background Antibody-mediated rejection (AMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available.

Methods We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with AMR C4d status, both indirect signs of complement activation, improve risk stratification at time of AMR. Hence, among 467 patients in whom 1 or more graft biopsies were performed between 2008 and 2015, we included 56 with AMR according to Banff '15 criteria. Using concurrent sera, we prospectively identified DSA by single-antigen beads (IgG and C1q) assays.

Results Antibody-mediated rejection C4d (+) (n = 28) was associated with preformed DSA (P = 0.007), whereas DSA C1q (+) (n = 25) cases had stronger IgG-DSA (P < 0.001). At AMR, graft function was similar between DSA C1q groups, but in the first year after, it improved in DSA C1q (−), whereas a steady decline was observed in DSA C1q (+) cases, remaining significantly lower from 1 year until 4 years after AMR. DSA C1q (+) was significantly associated with reduced graft survival (P = 0.021), whereas AMR C4d (+) was not (P = 0.550). Importantly, a similar negative impact of DSA C1q (+) on graft survival was observed within AMR C4d (+) (P = 0.040) and (−) (P = 0.036), cases. In multivariable analysis, DSA C1q (+) (hazard ratio, 3.939, P = 0.005) and de novo DSA (hazard ratio, 4.409, P = 0.033) were independent predictors of graft failure, but stronger IgG-DSA was not. Similar results were obtained considering C1q-DSA and IgG-DSA strength as continuous variables.

Conclusions C1q-DSA assessment at AMR can be a valuable tool in detecting patients with higher risk of graft failure.

This single center retrospective cross-sectional cohort study suggests that detection of C1q binding donor-specific antibodies (DSA) and de novo DSA at the time of antibody-mediated rejection are associated with reduced graft survival.

1 Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.

2 Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.

3 Centro do Sangue e Transplantação do Porto, Porto, Portugal.

Received 6 March 2018. Revision received 4 April 2018.

Accepted 28 April 2018.

This study was funded through a grant received from the Sociedade Portuguesa de Transplantação in 2014, used for reagents acquisition.

The authors declare no conflicts of interest.

Results presented in this paper have not been published previously in whole or part.

J.M. participated in the concept/design, data analysis/interpretation, drafting article, statistics, and data collection. S.S. participated in the data collection, data analysis/interpretation, and critical revision of the article. S.T. participated in the concept/design, data analysis/interpretation, data collection, and critical revision of the article. L.D. participated in the critical revision of article, approval of article, and data collection. L.S.M. participated in the critical revision of the article, approval of article, and data collection. I.F. participated in the concept/design, data analysis/interpretation, statistics, critical revision of article, and approval of the article. M.A. participated in the critical revision of article and data collection. S.P. participated in the critical revision of article and data collection. I.B. participated in the approval of the article. A.C.-H. participated in the critical revision of article, approval of article, data collection. A.C. participated in the approval of article.

Correspondence: Jorge Malheiro, Nephrology and Kidney Transplantation Department, Hospital de Santo António, Centro Hospitalar do Porto, Largo Prof, Abel Salazar 4099-001 Porto, Portugal. (jjorgemalheiro@gmail.com).

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.transplantjournal.com).

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.