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
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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. / 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.
In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Vol. 37, No. 6, 2022, p. 1099-1108.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - 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
AU - Sparding, Nadja
AU - Genovese, Federica
AU - Rasmussen, Daniel Guldager Kring
AU - Karsdal, Morten Asser
AU - Neprasova, Michaela
AU - Maixnerova, Dita
AU - Satrapova, Veronika
AU - Frausova, Doubravka
AU - Hornum, Mads
AU - Bartonova, Lenka
AU - Honsova, Eva
AU - Kollar, Marek
AU - Koprivova, Helena
AU - Hruskova, Zdenka
AU - Tesar, Vladimir
N1 - Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.
PY - 2022
Y1 - 2022
N2 - 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.
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.
KW - ANCA-associated vasculitis
KW - biomarkers
KW - chronic kidney disease
KW - IgA nephropathy
KW - interstitial fibrosis
UR - http://www.scopus.com/inward/record.url?scp=85131017522&partnerID=8YFLogxK
U2 - 10.1093/ndt/gfab163
DO - 10.1093/ndt/gfab163
M3 - Journal article
C2 - 33914059
AN - SCOPUS:85131017522
VL - 37
SP - 1099
EP - 1108
JO - Nephrology, Dialysis, Transplantation
JF - Nephrology, Dialysis, Transplantation
SN - 0931-0509
IS - 6
ER -
ID: 314075983