Work

Serum uric acid and incident sepsis risk: sex-specific nonlinear associations modified by kidney function in the UK Biobank

Year: 2026

Type: article

Abstract: Background Serum uric acid (SUA), the end product of purine metabolism, has opposing biological effects: it acts as an antioxidant at physiological concentrations but contributes to inflammation and endothelial dysfunction at elevated concentrations. Whether these effects translate into a concentration-dependent association with incident sepsis remains uncertain. Methods We included 466,753 UK Biobank participants. Sex-specific associations were examined using restricted cubic splines, two-piecewise Cox regression models, and multivariable Cox models. A three-way interaction among sex, SUA, and eGFR was tested to assess whether baseline eGFR modified the SUA-sepsis association differently by sex. Results During a mean follow-up of 13.5 years, 17,249 incident sepsis cases occurred. In males, SUA showed a U-shaped association with incident sepsis, with an inflection point at 5.69 mg/dL. Below this point, each 1-mg/dL increase in SUA was associated with lower sepsis risk (HR, 0.85; 95% CI, 0.81–0.89); above this point, higher SUA was associated with increased risk (HR, 1.05; 95% CI, 1.02–1.08). Males in the lowest and highest SUA sextiles had a higher risk than those in the reference sextile (Q1: HR, 1.26; 95% CI, 1.18–1.36; Q6: HR, 1.15; 95% CI, 1.08–1.24). In females, the association was modified by baseline eGFR: a U-shaped pattern was observed among those with eGFR < 90 mL/min/1.73 m², whereas among those with eGFR ≥ 90 mL/min/1.73 m², risk was elevated mainly at higher SUA concentrations. Conclusions Baseline SUA is associated with incident sepsis in a nonlinear, sex-specific, and kidney function-dependent manner. In males, both low and high SUA concentrations confer increased risk. In females, baseline eGFR modifies the association, with a U-shaped pattern among those with reduced kidney function and increased risk confined to higher SUA concentrations among those with preserved kidney function.

Source: Scientific Reports

DOI: 10.1038/s41598-026-72122-9

Authors: Zongjun Hu, Yaping Su, Xia Huang

Institutions: Chongqing University, Chongqing Cancer Hospital

Language: English

Topic: Gout, Hyperuricemia, Uric Acid

Subfield: Nephrology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690