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Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis

BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels...

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Autores principales: Sparding, Nadja, Genovese, Federica, Rasmussen, Daniel Guldager Kring, Karsdal, Morten Asser, Neprasova, Michaela, Maixnerova, Dita, Satrapova, Veronika, Frausova, Doubravka, Hornum, Mads, Bartonova, Lenka, Honsova, Eva, Kollar, Marek, Koprivova, Helena, Hruskova, Zdenka, Tesar, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130028/
https://www.ncbi.nlm.nih.gov/pubmed/33914059
http://dx.doi.org/10.1093/ndt/gfab163
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author Sparding, Nadja
Genovese, Federica
Rasmussen, Daniel Guldager Kring
Karsdal, Morten Asser
Neprasova, Michaela
Maixnerova, Dita
Satrapova, Veronika
Frausova, Doubravka
Hornum, Mads
Bartonova, Lenka
Honsova, Eva
Kollar, Marek
Koprivova, Helena
Hruskova, Zdenka
Tesar, Vladimir
author_facet Sparding, Nadja
Genovese, Federica
Rasmussen, Daniel Guldager Kring
Karsdal, Morten Asser
Neprasova, Michaela
Maixnerova, Dita
Satrapova, Veronika
Frausova, Doubravka
Hornum, Mads
Bartonova, Lenka
Honsova, Eva
Kollar, Marek
Koprivova, Helena
Hruskova, Zdenka
Tesar, Vladimir
author_sort Sparding, Nadja
collection PubMed
description BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. RESULTS: S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort. CONCLUSIONS: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.
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spelling pubmed-91300282022-05-25 Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis Sparding, Nadja Genovese, Federica Rasmussen, Daniel Guldager Kring Karsdal, Morten Asser Neprasova, Michaela Maixnerova, Dita Satrapova, Veronika Frausova, Doubravka Hornum, Mads Bartonova, Lenka Honsova, Eva Kollar, Marek Koprivova, Helena Hruskova, Zdenka Tesar, Vladimir Nephrol Dial Transplant Original Article BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. RESULTS: S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort. CONCLUSIONS: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys. Oxford University Press 2021-04-29 /pmc/articles/PMC9130028/ /pubmed/33914059 http://dx.doi.org/10.1093/ndt/gfab163 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://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
spellingShingle Original Article
Sparding, Nadja
Genovese, Federica
Rasmussen, Daniel Guldager Kring
Karsdal, Morten Asser
Neprasova, Michaela
Maixnerova, Dita
Satrapova, Veronika
Frausova, Doubravka
Hornum, Mads
Bartonova, Lenka
Honsova, Eva
Kollar, Marek
Koprivova, Helena
Hruskova, Zdenka
Tesar, Vladimir
Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
title Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
title_full Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
title_fullStr Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
title_full_unstemmed Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
title_short Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
title_sort endotrophin, a collagen type vi-derived matrikine, reflects the degree of renal fibrosis in patients with iga nephropathy and in patients with anca-associated vasculitis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130028/
https://www.ncbi.nlm.nih.gov/pubmed/33914059
http://dx.doi.org/10.1093/ndt/gfab163
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