Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients
Introduction: Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation. Methods: W...
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2020-09-01
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doaj-60a828c3c7b447bb946165403b13ff0c2020-11-25T03:16:37ZengElsevierKidney International Reports2468-02492020-09-015914481458Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant RecipientsInge Mertens0Hanny Willems1Elisabet Van Loon2Karin Schildermans3Kurt Boonen4Geert Baggerman5Dirk Valkenborg6Wilfried Gwinner7Dany Anglicheau8Marie Essig9Pierre Marquet10Maarten Naesens11Health Unit, Centre for Proteomics, VITO, Mol, Belgium; Centre for Proteomics, University of Antwerp, Antwerp, BelgiumHealth Unit, Centre for Proteomics, VITO, Mol, Belgium; Centre for Proteomics, University of Antwerp, Antwerp, BelgiumDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, BelgiumHealth Unit, Centre for Proteomics, VITO, Mol, Belgium; Centre for Proteomics, University of Antwerp, Antwerp, BelgiumHealth Unit, Centre for Proteomics, VITO, Mol, Belgium; Centre for Proteomics, University of Antwerp, Antwerp, BelgiumHealth Unit, Centre for Proteomics, VITO, Mol, Belgium; Centre for Proteomics, University of Antwerp, Antwerp, BelgiumDepartment of Mathematics and Statistics, Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Diepenbeek, BelgiumDepartment of Nephrology, Hannover Medical School, Hannover, GermanyDepartment of Nephrology and Kidney Transplantation, Adult Nephrology-Renal Transplant Service, Necker-Enfants Malades Hospital, Paris, FranceDepartment of Nephrology, CHU Limoges, Limoges, FranceDepartment of Nephrology, CHU Limoges, Limoges, France; Department of Nephrology, Laboratory of Medical Pharmacology, University of Limoges, Limoges, FranceDepartment of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium; Correspondence: Maarten Naesens, Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.Introduction: Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation. Methods: We performed a multicenter case-control study to identify a urinary biomarker for ABMR (training cohort, n = 249) and an independent, prospective multicenter cohort study for validation (n = 391). We used concomitant biopsies to classify the samples according to the Banff classification. After untargeted protein identification and quantification, we used a support vector machine to train the model in the training cohort. The primary endpoint was the diagnostic accuracy of the urinary biomarker for ABMR in the validation cohort. Results: We identified a set of 10 urinary proteins that accurately discriminated patients with (n = 60) and without (n = 189) ABMR in the training cohort with an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.96–1.00). The diagnostic accuracy was maintained in the validation cohort (AUC, 0.88; 95% CI, 0.8–0.93) for discriminating the presence (n = 43) from the absence (n = 348) of ABMR. The negative predictive value of the 10-protein marker set for exclusion of ABMR was 0.99, and the positive predictive value was 0.33. The diagnostic accuracy was independent of the reason for performing the biopsy, time after transplantation, and better than the accuracy of gross proteinuria (AUC, 0.76). Conclusions: We identified and validated a urinary protein biomarker set that can be used to exclude ABMR.http://www.sciencedirect.com/science/article/pii/S2468024920313413antibody-mediated rejectionnoninvasive biomarkerrenal transplantationurinary proteomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inge Mertens Hanny Willems Elisabet Van Loon Karin Schildermans Kurt Boonen Geert Baggerman Dirk Valkenborg Wilfried Gwinner Dany Anglicheau Marie Essig Pierre Marquet Maarten Naesens |
spellingShingle |
Inge Mertens Hanny Willems Elisabet Van Loon Karin Schildermans Kurt Boonen Geert Baggerman Dirk Valkenborg Wilfried Gwinner Dany Anglicheau Marie Essig Pierre Marquet Maarten Naesens Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients Kidney International Reports antibody-mediated rejection noninvasive biomarker renal transplantation urinary proteomics |
author_facet |
Inge Mertens Hanny Willems Elisabet Van Loon Karin Schildermans Kurt Boonen Geert Baggerman Dirk Valkenborg Wilfried Gwinner Dany Anglicheau Marie Essig Pierre Marquet Maarten Naesens |
author_sort |
Inge Mertens |
title |
Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients |
title_short |
Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients |
title_full |
Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients |
title_fullStr |
Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients |
title_full_unstemmed |
Urinary Protein Biomarker Panel for the Diagnosis of Antibody-Mediated Rejection in Kidney Transplant Recipients |
title_sort |
urinary protein biomarker panel for the diagnosis of antibody-mediated rejection in kidney transplant recipients |
publisher |
Elsevier |
series |
Kidney International Reports |
issn |
2468-0249 |
publishDate |
2020-09-01 |
description |
Introduction: Antibody-mediated rejection (ABMR) impacts kidney allograft outcome. The diagnosis is made based on findings from invasive kidney transplant biopsy specimens. The aim of this study was to identify a noninvasive urinary protein biomarker for ABMR after kidney transplantation. Methods: We performed a multicenter case-control study to identify a urinary biomarker for ABMR (training cohort, n = 249) and an independent, prospective multicenter cohort study for validation (n = 391). We used concomitant biopsies to classify the samples according to the Banff classification. After untargeted protein identification and quantification, we used a support vector machine to train the model in the training cohort. The primary endpoint was the diagnostic accuracy of the urinary biomarker for ABMR in the validation cohort. Results: We identified a set of 10 urinary proteins that accurately discriminated patients with (n = 60) and without (n = 189) ABMR in the training cohort with an area under the curve (AUC) of 0.98 (95% confidence interval [CI], 0.96–1.00). The diagnostic accuracy was maintained in the validation cohort (AUC, 0.88; 95% CI, 0.8–0.93) for discriminating the presence (n = 43) from the absence (n = 348) of ABMR. The negative predictive value of the 10-protein marker set for exclusion of ABMR was 0.99, and the positive predictive value was 0.33. The diagnostic accuracy was independent of the reason for performing the biopsy, time after transplantation, and better than the accuracy of gross proteinuria (AUC, 0.76). Conclusions: We identified and validated a urinary protein biomarker set that can be used to exclude ABMR. |
topic |
antibody-mediated rejection noninvasive biomarker renal transplantation urinary proteomics |
url |
http://www.sciencedirect.com/science/article/pii/S2468024920313413 |
work_keys_str_mv |
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