Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
The diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of “Increased Expression Of Thoroughly Validated Gene Transcripts/Classifiers Strongly Associated With AMR” as a diagnostic criteria.
Method
We used qRT-PCR for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27); biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts (AMRsusp, n = 49) and biopsies that would never meet criteria for AMR (No-AMR, n = 221).
Results
A 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score amongst the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low) (n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio for graft loss in the AMRsusp group (HR 1.109, p = 0.004 and HR 1.138, p = 0.012), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination respectively for graft loss when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort.
Conclusions
This study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of graft loss in biopsies that are suspicious for AMR but don’t meet full criteria.
The diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of “Increased Expression Of Thoroughly Validated Gene Transcripts/Classifiers Strongly Associated With AMR” as a diagnostic criteria.
Method
We used qRT-PCR for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27); biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts (AMRsusp, n = 49) and biopsies that would never meet criteria for AMR (No-AMR, n = 221).
Results
A 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score amongst the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low) (n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio for graft loss in the AMRsusp group (HR 1.109, p = 0.004 and HR 1.138, p = 0.012), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination respectively for graft loss when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort.
Conclusions
This study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of graft loss in biopsies that are suspicious for AMR but don’t meet full criteria.
Date Issued
2022-08
Date Acceptance
2021-06-17
Citation
Nephrology Dialysis Transplantation, 2022, 37 (8), pp.1576-1584
ISSN
0931-0509
Publisher
Oxford University Press
Start Page
1576
End Page
1584
Journal / Book Title
Nephrology Dialysis Transplantation
Volume
37
Issue
8
Copyright Statement
© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
License URL
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
https://academic.oup.com/ndt/article/37/8/1576/6329647
Grant Number
RDA28
Subjects
Science & Technology
Life Sciences & Biomedicine
Transplantation
Urology & Nephrology
acute rejection
chronic renal failure
gene expression
graft failure
kidney biopsy
DONOR-SPECIFIC ANTIBODIES
GENE-EXPRESSION
PROSPECTS
acute rejection
chronic renal failure
gene expression
graft failure
kidney biopsy
Antibodies
Biopsy
Graft Rejection
Graft Survival
Humans
Kidney Transplantation
Retrospective Studies
Humans
Antibodies
Biopsy
Kidney Transplantation
Retrospective Studies
Graft Rejection
Graft Survival
Urology & Nephrology
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2021-07-28