PMID- 33914059 OWN - NLM STAT- MEDLINE DCOM- 20220526 LR - 20230916 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 37 IP - 6 DP - 2022 May 25 TI - 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. PG - 1099-1108 LID - 10.1093/ndt/gfab163 [doi] AB - 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. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. FAU - Sparding, Nadja AU - Sparding N AUID- ORCID: 0000-0002-6979-0632 AD - Nordic Bioscience, Herlev, Denmark. AD - Faculty of Health and Medical Science, Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Genovese, Federica AU - Genovese F AD - Nordic Bioscience, Herlev, Denmark. FAU - Rasmussen, Daniel Guldager Kring AU - Rasmussen DGK AUID- ORCID: 0000-0003-1642-7482 AD - Nordic Bioscience, Herlev, Denmark. FAU - Karsdal, Morten Asser AU - Karsdal MA AD - Nordic Bioscience, Herlev, Denmark. FAU - Neprasova, Michaela AU - Neprasova M AD - Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. FAU - Maixnerova, Dita AU - Maixnerova D AD - Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. FAU - Satrapova, Veronika AU - Satrapova V AD - Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. FAU - Frausova, Doubravka AU - Frausova D AD - Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. FAU - Hornum, Mads AU - Hornum M AUID- ORCID: 0000-0002-0123-4007 AD - Department of Nephrology, Rigshospitalet, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Bartonova, Lenka AU - Bartonova L AD - Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. FAU - Honsova, Eva AU - Honsova E AD - Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. FAU - Kollar, Marek AU - Kollar M AD - Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. FAU - Koprivova, Helena AU - Koprivova H AD - Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. FAU - Hruskova, Zdenka AU - Hruskova Z AD - Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. FAU - Tesar, Vladimir AU - Tesar V AD - Department of Nephrology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Collagen Type VI) RN - 0 (Peptide Fragments) RN - 0 (endotrophin) SB - IM MH - *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications/pathology MH - Atrophy/complications/pathology MH - Collagen Type VI MH - Fibrosis MH - *Glomerulonephritis, IGA/pathology MH - Humans MH - Kidney/pathology MH - Peptide Fragments MH - *Renal Insufficiency, Chronic/complications PMC - PMC9130028 OTO - NOTNLM OT - ANCA-associated vasculitis OT - IgA nephropathy OT - biomarkers OT - chronic kidney disease OT - interstitial fibrosis EDAT- 2021/04/30 06:00 MHDA- 2022/05/27 06:00 PMCR- 2021/04/29 CRDT- 2021/04/29 12:26 PHST- 2020/12/22 00:00 [received] PHST- 2021/04/30 06:00 [pubmed] PHST- 2022/05/27 06:00 [medline] PHST- 2021/04/29 12:26 [entrez] PHST- 2021/04/29 00:00 [pmc-release] AID - 6259092 [pii] AID - gfab163 [pii] AID - 10.1093/ndt/gfab163 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2022 May 25;37(6):1099-1108. doi: 10.1093/ndt/gfab163.