Phenotype-specific dynamics of serum albumin and their impact on sepsis mortality

Aims: To assess the prognostic value of serial serum albumin measurements in septic patients, with a focus on different clinical phenotypes. Methods: We conducted a prospective observational study involving 254 patients with sepsis admitted to an Intermediate Care Unit in Italy (September 2022–June 2024). Patients were classified into four sepsis phenotypes (α, β, γ, δ), and serum albumin levels were measured daily over five days. The primary outcome was 30-day mortality. Logistic regression, Cox models, and AUROC analysis were used to evaluate associations between albumin dynamics, phenotypes, and outcomes. Results: The δ phenotype showed the lowest mean albumin levels (2.2 g/dL) and the highest mortality (45.4%), while phenotype α had the highest albumin and lowest mortality (3.6%). Each 1 g/dL increase in albumin was associated with a 63% mortality risk reduction (HR 0.37; 95% CI: 0.24–0.56). Albumin’s predictive performance was strongest in the δ phenotype (AUROC up to 0.95). Conclusion: Serial albumin monitoring may provide prognostic insights in sepsis, especially in phenotypes associated with endothelial dysfunction. These results are hypothesis-generating and may support more personalized treatment strategies.