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Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial

The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. Th...

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Autores principales: Yepes-Calderón, Manuela, Sotomayor, Camilo G., Rasmussen, Daniel Guldager Kring, Hijmans, Ryanne S., te Velde-Keyzer, Charlotte A., van Londen, Marco, van Dijk, Marja, Diepstra, Arjan, Berger, Stefan P., Karsdal, Morten Asser, Bemelman, Frederike J., de Fijter, Johan W., Kers, Jesper, Florquin, Sandrine, Genovese, Federica, Bakker, Stephan J. L., Sanders, Jan-Stephan, Van Den Born, Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600059/
https://www.ncbi.nlm.nih.gov/pubmed/33036366
http://dx.doi.org/10.3390/jcm9103216
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author Yepes-Calderón, Manuela
Sotomayor, Camilo G.
Rasmussen, Daniel Guldager Kring
Hijmans, Ryanne S.
te Velde-Keyzer, Charlotte A.
van Londen, Marco
van Dijk, Marja
Diepstra, Arjan
Berger, Stefan P.
Karsdal, Morten Asser
Bemelman, Frederike J.
de Fijter, Johan W.
Kers, Jesper
Florquin, Sandrine
Genovese, Federica
Bakker, Stephan J. L.
Sanders, Jan-Stephan
Van Den Born, Jacob
author_facet Yepes-Calderón, Manuela
Sotomayor, Camilo G.
Rasmussen, Daniel Guldager Kring
Hijmans, Ryanne S.
te Velde-Keyzer, Charlotte A.
van Londen, Marco
van Dijk, Marja
Diepstra, Arjan
Berger, Stefan P.
Karsdal, Morten Asser
Bemelman, Frederike J.
de Fijter, Johan W.
Kers, Jesper
Florquin, Sandrine
Genovese, Federica
Bakker, Stephan J. L.
Sanders, Jan-Stephan
Van Den Born, Jacob
author_sort Yepes-Calderón, Manuela
collection PubMed
description The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. β = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. β = 0.24 and 0.23, respectively) (p < 0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required.
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spelling pubmed-76000592020-11-01 Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial Yepes-Calderón, Manuela Sotomayor, Camilo G. Rasmussen, Daniel Guldager Kring Hijmans, Ryanne S. te Velde-Keyzer, Charlotte A. van Londen, Marco van Dijk, Marja Diepstra, Arjan Berger, Stefan P. Karsdal, Morten Asser Bemelman, Frederike J. de Fijter, Johan W. Kers, Jesper Florquin, Sandrine Genovese, Federica Bakker, Stephan J. L. Sanders, Jan-Stephan Van Den Born, Jacob J Clin Med Article The PRO-C6 assay, a reflection of collagen type VI synthesis, has been proposed as a non-invasive early biomarker of kidney fibrosis. We aimed to investigate cross-sectional and longitudinal associations between plasma and urine PRO-C6 and proven histological changes after kidney transplantation. The current study is a post-hoc analysis of 94 participants of the MECANO trial, a 24-month prospective, multicenter, open-label, randomized, controlled trial aimed at comparing everolimus-based vs. cyclosporine-based immunosuppression. PRO-C6 was measured in plasma and urine samples collected 6 and 24 months post-transplantation. Fibrosis was evaluated in biopsies collected at the same time points by Banff interstitial fibrosis/tubular atrophy (IF/TA) scoring and collagen staining (Picro Sirius Red; PSR); inflammation was evaluated by the tubulo-interstitial inflammation score (ti-score). Linear regression analyses were performed. Six-month plasma PRO-C6 was cross-sectionally associated with IF/TA score (Std. β = 0.34), and prospectively with 24-month IF/TA score and ti-score (Std. β = 0.24 and 0.23, respectively) (p < 0.05 for all). No significant associations were found between urine PRO-C6 and any of the biopsy findings. Fibrotic changes and urine PRO-C6 behaved differentially over time according to immunosuppressive therapy. These results are a first step towards non-invasive fibrosis detection after kidney transplantation by means of collagen VI synthesis measurement, and further research is required. MDPI 2020-10-07 /pmc/articles/PMC7600059/ /pubmed/33036366 http://dx.doi.org/10.3390/jcm9103216 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yepes-Calderón, Manuela
Sotomayor, Camilo G.
Rasmussen, Daniel Guldager Kring
Hijmans, Ryanne S.
te Velde-Keyzer, Charlotte A.
van Londen, Marco
van Dijk, Marja
Diepstra, Arjan
Berger, Stefan P.
Karsdal, Morten Asser
Bemelman, Frederike J.
de Fijter, Johan W.
Kers, Jesper
Florquin, Sandrine
Genovese, Federica
Bakker, Stephan J. L.
Sanders, Jan-Stephan
Van Den Born, Jacob
Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
title Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
title_full Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
title_fullStr Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
title_full_unstemmed Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
title_short Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
title_sort biopsy-controlled non-invasive quantification of collagen type vi in kidney transplant recipients: a post-hoc analysis of the mecano trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600059/
https://www.ncbi.nlm.nih.gov/pubmed/33036366
http://dx.doi.org/10.3390/jcm9103216
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