Serum high-density lipoprotein partially mediates the inverted L-shaped association between estimated glucose disposal rate and risk of kidney stones: A cross-sectional study from National Health and Nutrition Examination Survey.

ObjectiveKidney stones, affecting approximately 10% of adults worldwide, pose substantial clinical and economic burdens. Although insulin resistance is implicated in lithogenesis, the association between estimated glucose disposal rate, a surrogate marker of insulin sensitivity, and kidney stone risk, as well as the mediating role of lipid markers, remains unexplored.MethodsThis cross-sectional study analyzed data from 11,282 participants in the National Health and Nutrition Examination Survey (2007-2018). Estimated glucose disposal rate was calculated using waist circumference, hypertension status, and glycosylated hemoglobin. History of kidney stones was self-reported. Weighted logistic regression, restricted cubic spline models, and mediation analysis were used to assess associations, adjusting for sociodemographic, metabolic, and renal covariates.ResultsIn our study, the mean age of participants was 47.71 years, and the prevalence of kidney stones was 9.8%. In the fully adjusted multifactorial logistic regression model, participants in the highest quartile of estimated glucose disposal rate (Q4) were 44% less likely to develop stones than those in Q1 (odds ratio: 0.56, 95% confidence interval: 0.37-0.83; p = 0.005). Restricted cubic spline analysis identified a nonlinear, inverted L-shaped relationship between estimated glucose disposal rate and kidney stone risk, with an inflection point at an estimated glucose disposal rate of 8.72. Below this threshold, each 1-unit increase in estimated glucose disposal rate was associated with an 8% reduction in stone risk (odds ratio: 0.92, 95% confidence interval: 0.88-0.95; p < 0.001), whereas above 8.72, the risk was reduced by 31% for each 1-unit increase (odds ratio: 0.69, 95% confidence interval: 0.60-0.79; p < 0.001). Mediation analysis suggested that high-density lipoprotein mediated 5.72% of the total effect (p = 0.001), independent of body mass index, diabetes, and other confounders.ConclusionsEstimated glucose disposal rate and kidney stone risk demonstrated an inverted L-shaped association, with a threshold at 8.72. In addition, high-density lipoprotein partially mediated the association between estimated glucose disposal rate and kidney stones. These findings highlight the interaction between metabolic health and kidney stones and may guide personalized prevention strategies.