Accelerated biological aging and ultrasonography-detected nephrolithiasis burden: a two-center cross-sectional study

Background Chronological age does not fully reflect differences in physiological aging. Phenotypic Age (PhenoAge), derived from routine clinical biomarkers, integrates inflammatory, metabolic, hematologic, hepatic, and renal information. Previous studies have related accelerated biological aging to kidney-stone status, but its associations with distinct contemporaneous ultrasound-defined stone phenotypes and their consistency between health-examination centers remain uncertain. Objective To examine the association of PhenoAge acceleration (PhenoAgeAccel) with ultrasonography-detected nephrolithiasis and stone-burden phenotypes in two Chinese tertiary-hospital health-examination populations. Methods This two-center cross-sectional study included 2,689 adults undergoing routine health examinations from February to August 2026 in Shandong and Jiangsu. PhenoAge was reconstructed with the validated nine-biomarker algorithm. PhenoAgeAccel was defined as the center-specific residual from the regression of PhenoAge on chronological age and was standardized within center. Modified Poisson regression estimated prevalence ratios (PRs), multinomial logistic regression evaluated stone laterality and multiplicity, and restricted cubic splines assessed the dose–response shape. Center-specific, subgroup, and sensitivity analyses were used to assess the consistency of the findings. Results Nephrolithiasis was detected in 190 participants (7.07%); prevalence did not differ between Shandong (6.85%) and Jiangsu (7.29%; P = 0.705). Each 1-SD higher PhenoAgeAccel was associated with higher nephrolithiasis prevalence after full adjustment (PR, 1.29; 95% CI, 1.10–1.51; P = 0.002). The PR for the highest versus the lowest quartile was 1.89 (95% CI, 1.22–2.93; P = 0.005; P for trend = 0.005). The spline association was significant (P = 0.009) without evidence of non-linearity (P = 0.784). Relative to participants without stones, PhenoAgeAccel was associated with the multiple-stone category (OR, 1.39; 95% CI, 1.08–1.81; P = 0.012). Results for bilateral stones (36 cases; P = 0.223) were imprecise, and an association with maximum diameter was not statistically detected (P = 0.432). Center-specific PRs were 1.33 in Shandong (P = 0.021) and 1.26 in Jiangsu (P = 0.032), with no center interaction (P = 0.374). Conclusions Higher PhenoAgeAccel was associated with prevalent ultrasonography-detected nephrolithiasis and with both single- and multiple-stone categories versus no stones in two Chinese tertiary-hospital health-examination centers. Findings for bilaterality and maximum diameter were inconclusive. The cross-sectional data neither establish a causal contribution of biological aging to stone formation nor demonstrate a role for PhenoAgeAccel in clinical prediction or screening.