Soluble triggering receptor expressed on myeloid cells-1 as a predictive biomarker in sepsis: insights into cut-offs, mortality risk, and treatment guidance-secondary analysis of the Next GeneSiS-Trial.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is one of the more recently described biomarkers for sepsis and currently of great interest, as an inhibitor called nangibotide (Inotrem, Paris, France) for TREM-1 has made it into a phase 3 study for the treatment of sepsis. TREM-1, as a pattern recognition receptor (PRRs), plays a crucial role in the immune defense of the host. Several studies revealed promising results for soluble TREM-1 (sTREM-1) as a biomarker for outcome prediction. However, its usefulness in different subgroups of sepsis and the cut-off threshold at which patients are exposed to a higher risk of mortality have not yet been sufficiently investigated. METHODS: This study is a secondary analysis of data and sTREM-1 measurements from plasma samples obtained in the prospective, observational, non-interventional, multicentric Next GeneSiS-Trial (DRKS00011911). We aimed to characterize the role of sTREM-1 in septic and septic shock patients in a large cohort with regard to different pre-existing factors, infectious aspects and outcome parameters. Furthermore, we investigated the influence of sTREM-1 cut-offs previously described from Francois et al. on different outcome parameters. Therefore, data from 500 patients were analyzed. RESULTS: Median sTREM-1 values were statistically significant higher in patients with septic shock than in septic patients (406 (IQR;270–650) pg/mL vs. 293 (IQR;189–489) pg/mL; p < 0.001). Non-survivors, patients with the need of renal replacement therapy, mechanical ventilation or a positive Sepsis-Induced-Coagulopathy (SIC) score presented with statistically significant higher sTREM-1 values (p < 0.001). sTREM-1 levels were significantly higher in patients in the highest quartile for fluid balance and Sequential Organ Failure Assessment score, and significantly lower in those in the highest quartile for Horowitz Index and platelet count (PSSC). sTREM-1 levels showed slight but statistically significant differences based on the site of infection or blood culture results on day one; however, these differences were no longer detectable by day three. The best cut-off of sTREM-1 values to differentiate between survival and non-survival on day 28 was 408 (CI;297–505) pg/ml in our study. CONCLUSION: Elevated sTREM-1 concentrations particularly occur in patients with a high degree of organ damage, who are at high risk for adverse outcomes. In addition, the primary site of infection may be of relevance for the sTREM-1 increase. These characteristics support its suitability as a biomarker across different causes of sepsis and highlights its potential as a therapeutic target. A cut-off value exceeding 400 pg/mL has shown robust diagnostic performance across multiple studies. Our results support this observation, indicating that this threshold may be useful for future clinical and research applications.