Application of urinary peptide-biomarkers in trauma patients as a predictive tool for prognostic assessment, treatment and intervention timing.

Treatment of severely injured patients represents a major challenge, in part due to the unpredictable risk of major adverse events, including death. Preemptive personalized treatment aimed at preventing these events is a crucial objective of patient management; however, the currently available scoring systems provide only moderate guidance. Biomarkers from proteomics/peptidomics studies hold promise for improving the current situation, ultimately enabling precision medicine based on individual molecular profiles. To test the hypothesis that peptide biomarkers could predict patient outcomes in severely injured patients, we initiated a pilot study involving consecutive urine sampling (on days 0, 2, 5, 10, and 14) and subsequent peptidome analysis using capillary electrophoresis coupled to mass spectrometry (CE-MS) of 14 severely injured patients and two additional intensive care unit patients. The urine peptidomes of these patients were compared to those of age- and sex-matched controls. Moreover, previously established urinary peptide-based classifiers, CKD273, AKI204, and Cov50, were applied to the obtained peptidome data, and the association of the classifier's scores with a combined endpoint (death and/or kidney failure and/or respiratory insufficiency) was investigated. CE-MS peptidome analysis identified 191 significantly altered peptides in severely injured patients. A consistent increase in the abundance of peptides from A1AT, AHSG, and HBA1 was observed, while peptides derived from PIGR and UROM were consistently decreased. Most of the significant peptides (adjusted p < 0.05) were from COL1A1, and most were reduced in abundance. Two of the previously defined and validated peptidomic classifiers, CKD273 and AKI204, showed significant associations with the combined endpoint, which was not observed for the routine scores generally applied in the clinics. This prospective pilot study confirmed the hypothesis that urinary peptides provide information on patient outcomes and may guide personalized interventions in severely injured patients based on individual molecular changes. The results obtained allow the planning of a well-powered prospective trial investigating the value of urinary peptides in this context in more detail.