Background: The incidence of sepsis is high among patients in the intensive care units (ICU) and acute kidney injury (AKI) is a common complication of sepsis that contributes to increased mortality. Thymosin beta-4 (Tβ4) is an actin-sequestering protein that can prevent inflammation and fibrosis in several tissues. However, its functions in septic AKI remain unknown.
Methods: 98 consecutive hospitalized patients with confirmed sepsis were enrolled. Demographics, comorbidities, laboratory findings, and outcomes were collected and analyzed. Serum Tβ4 levels at ICU admission were measured and analyzed for evaluating the probability of AKI using the logistic regression. In addition, the effects of exogenous Tβ4 on kidney injury was also conducted in mice where a sepsis model was induced by lipopolysaccharide (LPS) intraperitoneal injection.
Results: Of the 98 patients with sepsis, 47 (48%) developed AKI. Patients with hypertension, diabetes, higher body mass index (BMI) and Sequential Organ Failure Assessment (SOFA) score were more likely to develop AKI. Among patients with AKI, hemoglobin, and Tβ4 were significantly decreased. Multivariate analysis showed decreased Tβ4, high SOFA, and high BMI to be independent risk factors for AKI in patients with sepsis. The overall mortality rate of the 98 septic patients was 20.4%, and the mortality rate of those with AKI was 29.8%. Kaplan-Meier analysis demonstrated that patients with AKI had a significantly higher risk of death. In particular, increasing AKI severity was associated with an increased risk of death. Furthermore, exogenous Tβ4 could reduce renal apoptosis and attenuated renal dysfunction, as well as reducing systemic inflammatory response through the prevention of the activation of NF-κB pathway in the sepsis model.
Conclusions: The combination of Tβ4, SOFA, and BMI could allow for timely detection of septic AKI. Exogenous Tβ4 could prevent kidney injury in sepsis.