Urinary Collagen Peptides Predict Mortality.

Organ fibrosis caused by the presence of excessive extracellular matrix (ECM) is related to mortality. Urinary peptide signatures were reported to be predictive of death in SARS-CoV-2 and chronic kidney disease. Such signatures were composed for 68% of collagen fragments. In this study, we examined whether urinary collagen peptides, potentially representing organ fibrosis, could predict mortality in patients with critical and non-critical conditions. Urinary proteomic data from 1012 patients with follow-up information from the CRIT-COV-U study were investigated for the association of collagen peptides with short-term mortality. Independent datasets from 9193 patients were used for validation, including 1719 patients sampled at intensive care unit (ICU) admission and 7474 patients with other diseases (outside the ICU). A total of 607 collagen peptides were significantly associated with mortality. A classifier based on 210 collagen peptides (COL210) predicting mortality was developed and validated in patients in the ICU (ICUHR: 2.64; 95% CI:1.71-4.10; p<0.001) and outside the ICU (Non-ICUHR: 2.16 95% CI: 1.47-3.17; p<0.001), showing strong associations to mortality regardless underlying conditions. This study demonstrates a link between the presence of ECM fragments in urine, specifically collagens, and increased mortality risk. Such a non-invasive collagen-based predictor of mortality may serve as a basis for proteomics-guided targeted intervention.