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

Author:

Sparding Nadja12ORCID,Genovese Federica1,Rasmussen Daniel Guldager Kring1ORCID,Karsdal Morten Asser1,Neprasova Michaela3,Maixnerova Dita3,Satrapova Veronika3,Frausova Doubravka3,Hornum Mads45ORCID,Bartonova Lenka6,Honsova Eva6,Kollar Marek6,Koprivova Helena7,Hruskova Zdenka3,Tesar Vladimir3

Affiliation:

1. Nordic Bioscience, Herlev, Denmark

2. Faculty of Health and Medical Science, Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

3. Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

4. Department of Nephrology, Rigshospitalet, Copenhagen, Denmark

5. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

6. Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

7. Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic

Abstract

Abstract 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.

Funder

Danish Research Foundation

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

Reference41 articles.

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1. Introduction;Biochemistry of Collagens, Laminins and Elastin;2024

2. The signals of the extracellular matrix;Biochemistry of Collagens, Laminins and Elastin;2024

3. Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials;European Journal of Heart Failure;2023-12-28

4. Endotrophin, a Key Marker and Driver for Fibroinflammatory Disease;Endocrine Reviews;2023-12-13

5. Evaluating Progression Risk in Patients With Immunoglobulin A Nephropathy;Kidney International Reports;2023-12

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