Association of serum uric acid, gout with incident sepsis: a large population-based prospective cohort study from UK Biobank

BACKGROUND: Sepsis remains a major cause of morbidity and mortality, yet current strategies for identifying susceptible individuals provide limited discriminatory performance. Although serum uric acid (SUA) and gout have been implicated in inflammatory and immune dysregulation, the associations of clinical urate phenotypes with incident sepsis risk and prognosis remain incompletely understood. METHODS: A prospective cohort analysis was conducted using UK Biobank data including 466,611 participants, in which clinical urate phenotypes (normal uric acid, asymptomatic HUA, and gout) were evaluated as primary exposures, with SUA quartiles and separate HUA and gout status analyses used as alternative exposure definitions, using multivariable Cox proportional hazards models, restricted cubic spline analyses, subgroup analyses, and sensitivity analyses including Fine-Gray competing-risk models. RESULTS: During a median follow-up of 14.53 years, 16,210 incident sepsis cases were identified. Compared with the normal uric acid group, asymptomatic HUA and gout were associated with higher sepsis risk after full adjustment, with HRs of 1.31 (95% CI 1.26-1.36; P < 0.001) and 1.35 (95% CI 1.25-1.46; P < 0.001), respectively. Sepsis risk increased progressively across SUA quartiles, with HRs of 1.06 (95% CI 1.01-1.12), 1.12 (95% CI 1.07-1.19), and 1.27 (95% CI 1.20-1.34) for Q2, Q3, and Q4 relative to Q1, respectively. Restricted cubic spline analysis shown a nonlinear association between SUA and sepsis risk (P < 0.001; P for nonlinearity < 0.001), with risk increasing above approximately 384.8 μmol/L. For 28-day all-cause mortality among sepsis patients, asymptomatic HUA remained associated with a higher risk in the fully adjusted model (HR 1.17, 95% CI 1.07-1.29, P < 0.01), whereas the association for baseline gout was not significant after adjustment. CONCLUSION: Higher SUA levels, HUA, and gout were associated with a higher incidence of sepsis in this observational cohort. Among patients who developed sepsis, asymptomatic HUA was associated with modestly higher short-term mortality, whereas this risk was not observed in the gout group.