Collagen type III formation but not degradation is associated with risk of kidney disease progression and mortality after acute kidney injury

Sparding, Nadja; Genovese, Federica; Karsdal, Morten Asser; Selby, Nicholas M

Abstract

Background

Acute kidney injury (AKI), a rapid decrease in kidney function, is associated with increased risk of adverse outcomes including development and progression of CKD. Kidney fibrosis is one of the pathological processes central to this AKI to CKD transition. Here we investigate the association of biomarkers of collagen type III turnover with adverse outcome following AKI.

Methods

We measured three biomarkers reflecting collagen type III formation (PRO-C3) and degradation (C3M and C3C) in plasma samples collected 1 year after an episode of AKI in 800 patients (392 patients with AKI and 408 non-AKI controls) from the prospective AKI Risk in Derby (ARID) study. Patients were followed until 3 years after the episode of AKI and the following outcomes were assessed: kidney disease progression, mortality, heart failure, CV events, and hospital readmission.

Results

PRO-C3 levels were elevated in the AKI group compared to the controls (P<0.001), whereas C3M and C3C levels were not different between groups. In multivariate models including common risk factors, PRO-C3 was prognostic for kidney disease progression and mortality in the AKI group and for heart failure in the control group. C3M and C3C were not prognostic for any of the investigated outcomes.

Conclusions

Circulating PRO-C3, a biomarker of fibroblast activity, was prognostic for kidney disease progression and mortality when measured one year after an episode of AKI. Biomarkers of fibroblast activity may help patient stratification after an episode of AKI by identifying patients at higher risk of kidney disease progression.

Citation

Sparding, N., Genovese, F., Karsdal, M. A., & Selby, N. M. (2025). Collagen type III formation but not degradation is associated with risk of kidney disease progression and mortality after acute kidney injury. Clinical Kidney Journal, 18(2), Article sfae413. https://doi.org/10.1093/ckj/sfae413

• Journal Article Type: Article
• Acceptance Date: Dec 5, 2024
• Online Publication Date: Dec 18, 2024
• Publication Date: 2025-02
• Deposit Date: Dec 22, 2024
• Publicly Available Date: Feb 17, 2025
• Journal: Clinical Kidney Journal
• Print ISSN: 2048-8505
• Electronic ISSN: 2048-8513
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Issue: 2
• Article Number: sfae413
• DOI: https://doi.org/10.1093/ckj/sfae413
• Keywords: acute kidney injury, biomarkers, collagen type III, fibroblasts, PRO-C3
• Public URL: https://nottingham-repository.worktribe.com/output/43213119
• Publisher URL: https://academic.oup.com/ckj/article/18/2/sfae413/7928125