Genetically predicted urinary sodium excretion and urolithiasis risk: a two-sample mendelian randomization study

Area of Science:

• Nephrology
• Genetics
• Epidemiology

Background:

• Observational studies suggest high sodium intake correlates with kidney stone formation.
• Previous research faced limitations due to confounding factors like diet and fluid intake.
• The direct causal role of urinary sodium in urolithiasis remained uncertain.

Purpose of the Study:

• To investigate the causal association between urinary sodium excretion and the risk of developing kidney stones.
• To leverage genetic data for a robust assessment, minimizing confounding factors.
• To provide genetic evidence supporting or refuting a direct link between urinary sodium and urolithiasis.

Main Methods:

• A two-sample Mendelian randomization analysis was employed.
• Genetic instruments for urinary sodium were derived from large-scale genome-wide association studies (UK Biobank, EBI).
• Urolithiasis data was sourced from the FinnGen R12 dataset, with inverse variance weighted method as primary analysis and sensitivity analyses performed.

Main Results:

• Genetically predicted higher urinary sodium excretion showed a significant association with increased urolithiasis risk (OR = 2.49).
• Results were replicated in an independent dataset, reinforcing the association (OR = 2.66).
• Sensitivity analyses indicated no significant horizontal pleiotropy or heterogeneity, supporting the primary findings.

Conclusions:

• The study provides genetic evidence suggesting higher urinary sodium excretion is a risk factor for kidney stones.
• These findings support current public health recommendations for sodium restriction in kidney stone prevention.
• The results highlight the potential direct role of urinary sodium in the pathogenesis of urolithiasis.