Molecular medicine (Cambridge, Mass.) · 2026
Urinary collagen type I degradation products as common fibrosis biomarkers in chronic diseases.
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Mina Ioanna K, Hussain Yaqza, Siwy Justyna, Catanese Lorenzo, Rupprecht Harald, Beige Joachim, Staessen Jan A, Metzger Jochen, Persson Frederik, Rossing Peter, Delles Christian, Schanstra Joost P, Bannaga Ayman, Vlahou Antonia, Mischak Harald, Arasaradnam Ramesh P, Latosinska Agnieszka
Аннотация
BACKGROUND: Fibrosis, characterised by excessive accumulation of collagen type I (COL1), is a common feature of chronic diseases, including liver diseases (LDs), chronic kidney disease (CKD) and heart failure (HF). COL1 degradation products can be detected in urine by proteomics/ peptidomics analyses and may serve as non-invasive biomarkers of fibrosis. We aimed to identify a common molecular signature of fibrosis across these diseases that may ultimately guide interventions to slow disease progression and prevent organ damage.
METHODS: Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n = 127), CKD (n = 263) or HF (n = 187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n = 110), CKD (n = 93), HF (n = 32) and controls (n = 643).
RESULTS: We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p < 0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p < 0.0001), 0.951 (95% CI 0.931-0.971, p < 0.0001) and 0.950 (95% CI 0.903-0.997, p < 0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p = 0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p = 0.045).
CONCLUSION: A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.
METHODS: Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n = 127), CKD (n = 263) or HF (n = 187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n = 110), CKD (n = 93), HF (n = 32) and controls (n = 643).
RESULTS: We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p < 0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p < 0.0001), 0.951 (95% CI 0.931-0.971, p < 0.0001) and 0.950 (95% CI 0.903-0.997, p < 0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p = 0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p = 0.045).
CONCLUSION: A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.