Erythropoietin as a critical prognostic indicator in ICU patients with sepsis: a prospective observational study

Erythropoietin (EPO), a glycoprotein hormone primarily produced in the kidneys, plays pleiotropic roles in hematopoietic and non-hematopoietic system. However, the clinical relevance of circulating EPO in sepsis progression and outcomes remains contentious and requires further elucidation.

Participants were categorized into three groups on the basis of EPO tertiles. The primary outcome was 28-day mortality. Multivariate Cox proportional regression analysis and restricted cubic spline regression were employed to evaluate the association between EPO levels and 28-day mortality in sepsis patients. Subgroup analyses were also conducted. Causal mediation analysis was conducted to explore the potential mediating role of EPO in the relationship between lactate and 28-day mortality.

A total of 267 patients (65.17% male) were included in the study. The 28-day and hospital mortality rates were 23.22 and 31.20%, respectively. Multivariate Cox regression revealed significantly higher 28-day and hospital mortality in the highest EPO tertile compared to the lowest (HR 2.93, 95% CI 1.20-7.22; HR 2.47, 95% CI 1.05-5.81, respectively). Restricted cubic spline analysis demonstrated a progressively increasing mortality risk with elevated EPO levels. Subgroup analyses confirmed the consistency and stability of the effect size and direction across different subgroups. Moreover, causal intermediary analysis revealed that the association between lactate and 28-day mortality was partially mediated by EPO, with a mediation ratio of 12.59%.

Elevated EPO levels in patients with sepsis are correlated with unfavorable prognoses and may function as a prognostic biomarker for adverse outcomes.