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.
ANCA-associated vasculitis
IgA nephropathy
biomarkers
chronic kidney disease
interstitial fibrosis
Journal
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
ISSN: 1460-2385
Titre abrégé: Nephrol Dial Transplant
Pays: England
ID NLM: 8706402
Informations de publication
Date de publication:
25 05 2022
25 05 2022
Historique:
received:
22
12
2020
pubmed:
30
4
2021
medline:
27
5
2022
entrez:
29
4
2021
Statut:
ppublish
Résumé
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). 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33914059
pii: 6259092
doi: 10.1093/ndt/gfab163
pmc: PMC9130028
doi:
Substances chimiques
Collagen Type VI
0
Peptide Fragments
0
endotrophin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1099-1108Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.
Références
J Cell Sci. 2015 Oct 1;128(19):3525-31
pubmed: 26377767
Mol Cell Proteomics. 2009 Oct;8(10):2296-307
pubmed: 19564150
Pediatr Nephrol. 2018 May;33(5):763-777
pubmed: 28624979
Lancet. 1968 Aug 17;2(7564):363-6
pubmed: 4173786
Am J Transplant. 2017 Jan;17(1):28-41
pubmed: 27862883
Nephrol Dial Transplant. 2004 Jun;19(6):1403-11
pubmed: 15069175
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
Kidney Int. 1994 Jun;45(6):1648-56
pubmed: 7933812
Nat Commun. 2014 Mar 19;5:3485
pubmed: 24647224
Adv Chronic Kidney Dis. 2010 Nov;17(6):469-79
pubmed: 21044769
Clin Kidney J. 2015 Jun;8(3):343-50
pubmed: 26034600
Clin J Am Soc Nephrol. 2017 Dec 7;12(12):1922-1929
pubmed: 28903970
Br J Clin Pharmacol. 2013 Oct;76(4):504-15
pubmed: 23802624
Chest. 2017 Jan;151(1):47-59
pubmed: 27575358
Int J Nephrol Renovasc Dis. 2018 Apr 12;11:137-148
pubmed: 29695925
J Am Soc Nephrol. 2010 Oct;21(10):1628-36
pubmed: 20616173
J Biol Chem. 2019 Sep 13;294(37):13769-13780
pubmed: 31346034
Fibrogenesis Tissue Repair. 2014 Mar 28;7(1):4
pubmed: 24678881
JCI Insight. 2016 Jan 21;1(1):e84916
pubmed: 27699213
Histochem J. 1996 May;28(5):385-90
pubmed: 8818685
Diabetes Care. 2018 Jul;41(7):1493-1500
pubmed: 29643059
J Nephrol. 2015 Feb;28(1):39-49
pubmed: 24756969
Crit Rev Oncol Hematol. 2004 Mar;49(3):199-202
pubmed: 15036260
Kidney Int. 2006 Nov;70(10):1694-705
pubmed: 16969387
Nephrol Dial Transplant. 2002 Apr;17(4):587-96
pubmed: 11917050
J Am Soc Nephrol. 2018 Nov;29(11):2722-2733
pubmed: 30279273
Sci Rep. 2017 Dec 11;7(1):17328
pubmed: 29229941
Hum Pathol. 1970 Dec;1(4):631-41
pubmed: 5521736
Semin Nephrol. 2004 May;24(3):179-96
pubmed: 15156525
Am J Physiol Gastrointest Liver Physiol. 2015 May 15;308(10):G807-30
pubmed: 25767261
PLoS One. 2017 Apr 12;12(4):e0175200
pubmed: 28403201
Nephrol Dial Transplant. 2014 Sep;29(9):1728-32
pubmed: 24578468
Nephrol Dial Transplant. 1998 Feb;13(2):305-12
pubmed: 9509439
Pediatr Nephrol. 2015 Feb;30(2):189-92
pubmed: 25318618
Kidney Int. 2017 May;91(5):1014-1021
pubmed: 28341274
Clin J Am Soc Nephrol. 2017 Oct 6;12(10):1680-1691
pubmed: 28842398
Biochem Biophys Res Commun. 2002 Jan 18;290(2):743-8
pubmed: 11785962
J Clin Invest. 2012 Nov;122(11):4243-56
pubmed: 23041627
PLoS One. 2015 Dec 07;10(12):e0144525
pubmed: 26641456
Clin J Am Soc Nephrol. 2014 Mar;9(3):617-25
pubmed: 24071652
Expert Opin Investig Drugs. 2018 May;27(5):491-496
pubmed: 29718732