Clinical Significance of Elevated Xanthine Dehydrogenase Levels and Hyperuricemia in Patients with Sepsis

Abstract

Patient outcomes for severe sepsis and septic shock remain poor. Excessive oxidative stress accelerates organ dysfunction in severe acute illnesses. Uric acid (UA) is the most abundant antioxidant. We hypothesized that UA and related molecules, which play a critical role in antioxidant activity, might be markers of oxidative stress in sepsis. The study aimed to clarify the clinical significance of UA and the relationship between UA, molecules related to UA, and outcomes by measuring blood UA, xanthine dehydrogenase (XDH), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels over time. Blood UA levels in septic patients were correlated with the SOFA score (ρ = 0.36, p < 0.0001) and blood XDH levels (ρ = 0.27, p < 0.0001). Blood XDH levels were correlated with the SOFA score (ρ = 0.59, p < 0.0001) and blood 8-OHdG levels (ρ = −0.32, p < 0.0001). Blood XDH levels were persistently high in fatal cases. Blood XDH level (OR 8.84, 95% CI: 1.42–91.2, p = 0.018) was an independent factor of poor outcomes. The cutoff of blood XDH level was 1.38 ng/mL (sensitivity 92.8%, specificity 61.9%), and those 1.38 ng/mL or higher were associated with a significantly reduced survival rate (blood XDH level > 1.38 ng/mL: 23.7%, blood XDH level < 1.38 ng/mL: 96.3%, respectively, p = 0.0007). Elevated UA levels due to elevated blood XDH levels in sepsis cases may reduce oxidative stress. Countermeasures against increased oxidative stress in sepsis may provide new therapeutic strategies.