Dataset Information

Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients.

ABSTRACT:

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

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

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

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.

SUBMITTER: Genovese F

PROVIDER: S-EPMC7886548 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients.

Genovese Federica F Rasmussen Daniel Guldager Kring DGK Karsdal Morten A MA Jesky Mark M Ferro Charles C Fenton Anthony A Cockwell Paul P

Clinical kidney journal 20200114 2

<h4>Background</h4>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.<h4>Methods</h ...[more]

PMID: 33623684

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Dataset Information

Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients.

Background

Methods

Results

Conclusions

Publications

Imbalanced turnover of collagen type III is associated with disease progression and mortality in high-risk chronic kidney disease patients.

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