Sex-Specific Associations Between Hyperuricemia and Kidney Stone Disease in a Large Taiwanese Cohort

<b>Background:</b> Kidney stone disease (KSD) is a growing global health issue, while hyperuricemia has been linked to various health conditions. This study aimed to explore the association between hyperuricemia and KSD. <b>Methods:</b> This study analyzed the data of 118,963 generally healthy participants aged 30-70 years from the Taiwan Biobank. KSD was defined based on self-reported diagnoses, and hyperuricemia was defined as a serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women. Key variables including age, sex, body mass index, lifestyle factors, presence of hypertension, diabetes, and chronic kidney disease were recorded. Statistical analysis was conducted using descriptive statistics and logistic regression to evaluate the association between hyperuricemia and KSD. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were reported, with statistical significance set at p < 0.05. An additional causal mediation analysis was performed to assess the mediating role of gout. <b>Results:</b> Among the 118,963 participants, 23,094 (19.4%) had hyperuricemia. Those with hyperuricemia were older, had a higher body mass index, and were more likely to smoke, consume alcohol, and have elevated blood pressure. They also had higher rates of comorbidities such as hypertension, diabetes, metabolic syndrome, chronic kidney disease, and gout, along with worse laboratory profiles. Multivariable analysis revealed that hyperuricemia was significantly associated with an increased risk of KSD (OR: 1.155, 95% CI: 1.089-1.224, p < 0.001). When stratified into four exposure groups, the prevalence of KSD was 5.4% in participants without hyperuricemia or gout, 8.5% in those with hyperuricemia alone, 17.0% in those with gout alone, and 15.7% in those with both conditions; the adjusted ORs were 1.178, 1.522, and 1.505, respectively, compared with the reference group. The risk was more pronounced in females, particularly those in higher uric acid quartiles, whereas in males, the association was weaker and became nonsignificant after full adjustments. Mediation analysis further indicated that gout explained approximately 24% of the association between hyperuricemia and KSD, while the direct effect of hyperuricemia on KSD remained significant. <b>Conclusion:</b> Hyperuricemia was an independent risk factor for KSD in this large Taiwanese cohort study, with a stronger association observed in females. Gout partially mediates this relationship, suggesting overlapping yet distinct pathways linking hyperuricemia to kidney stone formation. These findings underscore the importance of sex-specific management strategies for KSD. Routine monitoring of serum uric acid levels is recommended to mitigate KSD risk, especially among high-risk individuals. Future research should focus on elucidating the long-term impact of hyperuricemia on KSD and tailoring prevention strategies to regional and population-specific needs.