Sex-Specific Mediators of Serum Uric Acid Reduction Following Laparoscopic Sleeve Gastrectomy: A Retrospective Longitudinal Study

Hyperuricemia is highly prevalent among individuals with obesity and is associated with insulin resistance, chronic kidney disease, and cardiovascular risk. Although laparoscopic sleeve gastrectomy (LSG) reduces serum uric acid (SUA), the underlying mechanisms remain unclear. Emerging evidence suggests that sex differences influence metabolic regulation, including insulin secretion and renal urate handling. This study investigates one-year changes in SUA following LSG and explores sex-specific determinants. This retrospective cohort study included 268 patients (96 males, 172 females) undergoing LSG between 2014 and 2025. Clinical and laboratory parameters were collected at baseline and 12 months, with changes defined as baseline minus postoperative values. Sex-stratified univariate screening (P < 0.10) and backward multivariate regression identified independent predictors of SUA reduction. In females, bootstrap mediation analysis (5,000 resamples) assessed whether C-peptide and estimated glomerular filtration rate (eGFR) mediated the relationship between weight loss and SUA reduction. Baseline SUA was higher in males than females (479.8 vs. 406.9 µmol/L, P < 0.001). At 12 months, females exhibited greater absolute and relative SUA reductions (both P < 0.001). Baseline SUA and percent total weight loss (%TWL) were independent predictors in both sexes. In females, ΔeGFR remained significant (P = 0.007), while ΔC-peptide showed a trend (P = 0.063). Mediation analysis demonstrated that %TWL indirectly reduced SUA via ΔC-peptide (β = 0.251, 95% CI: 0.009–0.562), accounting for 9.2% of the total effect. SUA reduction following LSG exhibits sex-specific patterns. In females, the association between weight loss and SUA reduction was partially mediated by reductions in C-peptide, while changes in eGFR were independently associated with SUA reduction. Trial registration: ClinicalTrials.gov NCT04548232. LSG significantly reduces SUA, with greater reductions in females than in males. Baseline SUA and %TWL are independent predictors of SUA reduction in both sexes. In females, SUA improvement is partly mediated by reduced C-peptide and independently associated with renal function (ΔeGFR).