TRAIL and RIPK3 Do Not Predict Mortality and Acute Kidney Injury in Critically Ill Patients at Admission to the Intensive Care Unit-A Single-Center Cohort Study.

TNF-related apoptosis-inducing ligand (TRAIL), a protein involved in apoptosis, and receptor-interacting serine/threonine protein kinase-3 (RIPK3), implicated in necroptosis, are known to change during organ damage and have been studied as prognostic markers in sepsis; however, cell death mechanisms also play a role in other critical illnesses. This study aimed to assess the utility of TRAIL and RIPK3 in predicting mortality and acute kidney injury (AKI) among unselected intensive care unit (ICU) patients. We performed a single-center prospective cohort study including 142 consecutive ICU admissions, collecting blood samples for TRAIL and RIPK3 measurement within 24 h of admission. The primary endpoints were in-hospital mortality and incident AKI during the ICU stay, with additional analysis of mortality over a two-year follow-up. Neither TRAIL nor RIPK3 levels at admission were significantly associated with in-hospital mortality, long-term mortality, or AKI incidence. However, higher RIPK3 levels correlated with shorter time to AKI occurrence. These results suggest that despite earlier evidence supporting their prognostic value in sepsis, TRAIL and RIPK3 did not reliably predict outcomes in a heterogeneous ICU population, underscoring the complexity of critical illness and the need for multiparametric biomarker strategies to improve risk stratification.