Late Antibody-Mediated Rejection in a Large Cross-Sectional Cohort of Kidney Transplant Recipients – Results of the Screening Phase of the BORTEJECT Study
1Nephrology and Dialysis, Medical University Vienna, Vienna, Austria
2Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria
3Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria
44Division of Nephrology and Transplant Immunology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Meeting: 2015 American Transplant Congress
Abstract number: 96
Keywords: Alloantibodies, Biopsy, Gene expression, Rejection
Session Information
Date: Sunday, May 3, 2015
Session Name: Concurrent Session: Kidney Antibody Mediated Rejection II
Session Time: 4:00pm-5:30pm
Presentation Time: 5:12pm-5:24pm
Location: Terrace I-III
Antibody-mediated rejection (ABMR) is well established to be a leading cause of graft failure. Here, we investigated the prevalence of late ABMR in a large cohort of kidney recipients. This RCT (BORTEJECT study; NCT01873157) was designed to systematically investigate the effect of proteasome inhibition on the course of late AMR.
The BORTEJECT study includes a cross-sectional screening of 1,000 kidney allograft recipients [inclusion criteria: functioning graft at ≥180 days; eGFR >20 ml/min/1.73 m2] to identify 44 subjects with late AMR that are eligible for inclusion in a randomized double-blind placebo-controlled trial. All patients were screened for the presence of donor-specific antibodies (DSA) applying Luminex technology. DSA+ recipients were subjected to protocol biopsies being analyzed on the presence of pathological and molecular features consistent with ABMR.
714 transplant recipients underwent ABMR screening (median 6.5 years post-TX). 101 (14%) were DSA-positive (HLA I: n=30, HLA II: n=53, HLA I and II: n=18. 78 DSA+ recipients were subjected to protocol biopsies. 44 of them (6% of the overall cohort) showed microcirculation injury consistent with acute and/or chronic active ABMR, in the presence (n=15) or absence (n=29) of capillary C4d staining (40 of them were enrolled in the intervention trial). Gene expression patterns revealed tight associations between morphology and molecular ABMR scores. While baseline kidney parameters were comparable between ABMR+/- patients, we found significant differences regarding levels of DSA binding [median MFI in ABMR+ vs. ABMR- 4,197 (IQR 2,039-12,170) vs. 1,622 (1,205-3,446), respectively; P<0.001]. ROC curves revealed moderate predictive accuracy of DSA MFI with respect to ABMR diagnosis (AUC: 0.75).
The results of this cross-sectional study suggest a comparably low prevalence of late ABMR (<10%). The more prevalent finding of circulating DSA (14%) may not necessarily associate with ABMR, especially in patients with low antibody levels.
To cite this abstract in AMA style:
Eskandary F, Bond G, Regele H, Kozakowski N, Kikic Z, Wahrmann M, Haslacher H, Oberbauer R, Ramassar V, Halloran P, Böhmig G. Late Antibody-Mediated Rejection in a Large Cross-Sectional Cohort of Kidney Transplant Recipients – Results of the Screening Phase of the BORTEJECT Study [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/late-antibody-mediated-rejection-in-a-large-cross-sectional-cohort-of-kidney-transplant-recipients-results-of-the-screening-phase-of-the-borteject-study/. Accessed April 7, 2020.« Back to 2015 American Transplant Congress