Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients.
CKD
ESRD
biomarkers
interstitial fibrosis
prognosis
Journal
Clinical kidney journal
ISSN: 2048-8505
Titre abrégé: Clin Kidney J
Pays: England
ID NLM: 101579321
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
22
08
2019
accepted:
05
11
2019
entrez:
24
2
2021
pubmed:
25
2
2021
medline:
25
2
2021
Statut:
epublish
Résumé
Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the relationship between fragments reflecting active formation (PRO-C3) and degradation (C3M) of COL3 and CKD disease progression and mortality in a prospective cohort of CKD patients. We measured PRO-C3 and C3M in urine (uPRO-C3 and uC3M) and serum (sPRO-C3 and sC3M) of 500 patients from the Renal Impairment in Secondary Care study. Disease progression was defined as a decline in estimated glomerular filtration rate >30% or the start of renal replacement therapy within 12 and 30 months. Levels of uC3M/creatinine decreased, whereas levels of uPRO-C3/creatinine and sPRO-C3 increased with increasing CKD stage. uC3M/creatinine was inversely and independently associated with disease progression by 12 months {odds ratio [OR] 0.39 [95% confidence interval (CI) 0.18-0.83]; P = 0.01 per doubling of uC3M/creatinine} with development of end-stage renal disease [hazard ratio (HR) 0.70 (95% CI 0.50-0.97); P = 0.03 per doubling of uC3M/creatinine]. sPRO-C3 at baseline was independently associated with increased mortality [HR 1.93 (95% CI 1.21-3.1); P = 0.006 per doubling of sPRO-C3] and disease progression by 30 months [OR 2.16 (95% CI 1.21-3.84); P = 0.009 per doubling of sPRO-C3]. Dynamic products of COL3 formation and degradation were independently associated with CKD progression and mortality and may represent an opportunity to link pathological processes with targeted treatments against fibrosis.
Sections du résumé
BACKGROUND
BACKGROUND
Tubulointerstitial fibrosis is a major pathological feature in chronic kidney disease (CKD) and collagen type III (COL3) is a major component of the renal fibrotic scar. We hypothesized that a dysregulated turnover of COL3 is an important determinant of CKD progression. We assessed the relationship between fragments reflecting active formation (PRO-C3) and degradation (C3M) of COL3 and CKD disease progression and mortality in a prospective cohort of CKD patients.
METHODS
METHODS
We measured PRO-C3 and C3M in urine (uPRO-C3 and uC3M) and serum (sPRO-C3 and sC3M) of 500 patients from the Renal Impairment in Secondary Care study. Disease progression was defined as a decline in estimated glomerular filtration rate >30% or the start of renal replacement therapy within 12 and 30 months.
RESULTS
RESULTS
Levels of uC3M/creatinine decreased, whereas levels of uPRO-C3/creatinine and sPRO-C3 increased with increasing CKD stage. uC3M/creatinine was inversely and independently associated with disease progression by 12 months {odds ratio [OR] 0.39 [95% confidence interval (CI) 0.18-0.83]; P = 0.01 per doubling of uC3M/creatinine} with development of end-stage renal disease [hazard ratio (HR) 0.70 (95% CI 0.50-0.97); P = 0.03 per doubling of uC3M/creatinine]. sPRO-C3 at baseline was independently associated with increased mortality [HR 1.93 (95% CI 1.21-3.1); P = 0.006 per doubling of sPRO-C3] and disease progression by 30 months [OR 2.16 (95% CI 1.21-3.84); P = 0.009 per doubling of sPRO-C3].
CONCLUSIONS
CONCLUSIONS
Dynamic products of COL3 formation and degradation were independently associated with CKD progression and mortality and may represent an opportunity to link pathological processes with targeted treatments against fibrosis.
Identifiants
pubmed: 33623684
doi: 10.1093/ckj/sfz174
pii: sfz174
pmc: PMC7886548
doi:
Types de publication
Journal Article
Langues
eng
Pagination
593-601Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.
Références
Liver Int. 2015 Feb;35(2):429-37
pubmed: 25308921
Liver Int. 2018 Feb;38 Suppl 1:2-6
pubmed: 29427496
Expert Opin Ther Targets. 2008 Jun;12(6):667-76
pubmed: 18479214
Am J Kidney Dis. 2012 Jun;59(6):865-73
pubmed: 22497792
Fibrogenesis Tissue Repair. 2014 Mar 28;7(1):4
pubmed: 24678881
Nat Rev Nephrol. 2011 Oct 18;7(12):684-96
pubmed: 22009250
Nephrol Dial Transplant. 2015 Jul;30(7):1112-21
pubmed: 25784725
Am J Epidemiol. 1999 Feb 1;149(3):261-7
pubmed: 9927222
J Am Soc Nephrol. 2015 Aug;26(8):1999-2010
pubmed: 25589610
J Magn Reson Imaging. 2015 Oct;42(4):990-8
pubmed: 25630829
Curr Opin Nephrol Hypertens. 2015 May;24(3):217-23
pubmed: 26066472
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
Lancet. 2018 Mar 24;391(10126):1174-1185
pubmed: 29519502
Aliment Pharmacol Ther. 2018 Jul;48(2):179-189
pubmed: 29851098
Nat Rev Nephrol. 2014 May;10(5):290-6
pubmed: 24642801
Clin Biochem. 2010 Jul;43(10-11):899-904
pubmed: 20380828
BMC Nephrol. 2013 Apr 25;14:95
pubmed: 23617441
Kidney Int. 2006 Jan;69(2):213-7
pubmed: 16408108
Clin Radiol. 2014 Nov;69(11):1117-22
pubmed: 25062924
Am J Transl Res. 2013 Apr 19;5(3):303-15
pubmed: 23634241
Nephrol Dial Transplant. 1997 Sep;12(9):1883-9
pubmed: 9306339
PLoS One. 2017 Apr 21;12(4):e0175898
pubmed: 28430784
Nephrol Dial Transplant. 2016 Mar;31(3):472-9
pubmed: 26311218
Am J Cardiol. 2015 May 1;115(9):1311-7
pubmed: 25769628
Mol Cell Proteomics. 2010 Nov;9(11):2424-37
pubmed: 20616184
Adv Drug Deliv Rev. 2003 Nov 28;55(12):1531-46
pubmed: 14623400
Nat Rev Nephrol. 2010 Nov;6(11):643-56
pubmed: 20838416