Abstract: FR-PO1091
Dysregulation of the Plasma Metabolome Profile in Kidney Stone Formers
Session Information
- Health Maintenance, Nutrition, and Metabolism
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1500 Health Maintenance, Nutrition, and Metabolism
Authors
- Zhou, Le-Ting, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Wang, Liang, Wuxi People's Hospital, Wuxi, Jiangsu, China
- Rule, Andrew D., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Koo, Kevin, Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Larson, Nicholas B., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
Kidney stones are a widely prevalent disorder associated with a range of metabolomic disorders, some of which may be unknown. Thus, this study examined the relationship between kidney stones and the blood metabolome, especially lipids, in a large existing cohort.
Methods
Univariate and multivariable analysis strategies were employed to examine the relationship of NMR-measured plasma metabolites (n=150) with kidney stones among persons in the UK Biobank (n=186,362). The genetic components of traits of interest were evaluated through genome-wide association studies (GWAS), followed by secondary genetic association analyses.
Results
Significant univariate associations with kidney stones were observed for 68 of the 150 metabolites. After adjustments for body mass index (BMI) or waist-hip ratio (WHR), high-density lipoprotein (HDL) lipids remained downregulated, whereas very low-density lipoprotein (VLDL) lipids remained upregulated in stone formers. Mendelian randomization analysis revealed a genetic propensity to obesity associated with kidney stones, higher levels of triglycerides (a surrogate for VLDL lipids), higher atherogenic index of plasma (AIP), and lower HDL cholesterol (a surrogate for HDL lipids). Linkage disequilibrium score regression demonstrated a moderate genetic correlation between kidney stones and lipid metabolites. Adjustments for BMI or WHR attenuated these correlations, particularly for HDL. A shared risk locus near FGFR4 on chromosome 5 was identified after BMI adjustment between kidney stones and AIP that lost genome-wide significance after further adjustment for WHR.
Conclusion
Kidney stones are associated with lipid disorders, particularly low HDL and high VLDL. However, much of these associations are due to central obesity, which leads to both kidney stones and lipid disorders.
Workflow of the Study
Funding
- NIDDK Support