Association between accelerated biological aging and kidney stones and role of insulin resistance: a cross-sectional NHANES study

Background: Advanced biological aging is associated with an increased risk of adverse health effects. However, the association between biological aging acceleration (BAA) and kidney stone (KS) disease remains unclear. This study aimed to examine the association between BAA and KS and to assess whether insulin resistance (IR) mediates this association. Methods: A total of 10,227 non-pregnant adults (mean age 47.96 years, 50.03% male) from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 cycles were included in this cross-sectional study. Biological age was measured using the Klemera-Doubal method biological age (KDM-BA) and phenotypic age (PhenoAge) algorithms, and BAA was quantified by residual analysis and compared with chronological age. IR was assessed using five surrogates: the triglyceride-glucose (TyG) index, TyG-waist circumference (TyG-WC), TyG-waist-to-height ratio (TyG-WHtR), TyG-body mass index (TyG-BMI), and the metabolic score for insulin resistance (METS-IR). The relationships between BAA, IR surrogates, and KS were investigated using multivariable logistic regression models. To find out if IR mediates the association between BAA and KS, a mediation study was conducted. Results: After adjusting for all covariates, adults in the highest KDM-BA acceleration tertile had a 21% [odds ratio (OR): 1.21, 95% confidence interval (CI): 1.02-1.44] increased risk of KS compared with those in the lowest tertile. The multivariable-adjusted OR for KS comparing participants in the extreme PhenoAge acceleration tertiles was 1.77 (95% CI: 1.47-2.13). Mediation analyses indicated that the five IR surrogates statistically mediated part of the association between PhenoAge acceleration and KS, with the mediated proportions ranging from 1.67% to 29.34% (all P