Abstract: TH-PO0632
Adiposity Increases Kidney Stone Disease Risk via Renal Fat Depots and Natriuresis
Session Information
- Genetic Diseases of the Kidneys: Complex Kidney Traits
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Complex Kidney Traits
Authors
- Lovegrove, Catherine E., University of Oxford Nuffield Department of Surgical Sciences, Oxford, England, United Kingdom
- Thanaj, Marjola, University of Westminster, London, England, United Kingdom
- Aggarwal, Prashant, University of Oxford Nuffield Department of Surgical Sciences, Oxford, England, United Kingdom
- Basty, Nicolas, University of Westminster, London, England, United Kingdom
- Whitcher, Brandon, University of Westminster, London, England, United Kingdom
- Bell, Jimmy D, University of Westminster, London, England, United Kingdom
- Thomas, Elizabeth Louise, University of Westminster, London, England, United Kingdom
- Howles, Sarah, University of Oxford Nuffield Department of Surgical Sciences, Oxford, England, United Kingdom
Background
Higher body-mass-index (BMI) and waist-hip ratio (WHR) increase kidney stone disease (KSD) risk. We hypothesised that adiposity alters renal fat depots to cause KSD.
Methods
Renal sinus fat volumes (RSF) were measured in 3D-MRI data (UK Biobank). KSD was defined using ICD, OPCS, primary care, and self-report codes. Cox proportional hazards models assessed associations with incident KSD. Least Absolute Shrinkage and Selection Operator (LASSO) regression and stability selection identified determinants of RSF and KSD-relevant risk factors.
We investigated causality using Mendelian randomisation (MR) with genome-wide association studies of KSD (24,167 cases; 876,673 controls-UK Biobank/FinnGen), BMI and WHR (N=806,834 and 697,734, respectively-UK Biobank/GIANT), and urine sodium and creatinine (N=331,667 -UK Biobank).
Results
Of 52,951 participants with 3D-MRI data, 1,601 had prevalent and 95 had incident KSD. Higher RSF associates with KSD (HR=1.31, 95% CI=1.07-1.61, P<0.05, Fig 1), BMI, and WHR (ß=0.37 and 0.17, respectively; P<0.05). LASSO regression with stability selection identifies BMI, WHR, and urine sodium as predictors of RSF suggesting that changes in urine sodium may mediate effects of adiposity on KSD risk.
MR analyses reveal that higher BMI, not WHR, increases urine sodium (ß=6.93, p=8.13x10-27). After adjusting for urine creatinine, higher urine sodium increases KSD risk (OR per 43.24mmol/L higher urine sodium=1.03, 95%CI=1.02-1.05, p=2.00x10-4). Mediation MR indicates that natriuresis causes ~37% of the effect of BMI on KSD risk (Fig 2).
Conclusion
Adiposity influences KSD risk by altering RSF and urine sodium. Targeting adiposity-related changes in sodium excretion may prevent KSD.
Hazard ratios for incident kidney stone disease
Mediation-MR:effects of BMI on urine sodium & KSD
Funding
- Commercial Support – This research was conducted using the UK Biobank Resource (Application Numbers 44584 and 83942).