Abstract
Objective
To delineate the role of the urinary metabolome in the genesis of urinary stone disease
(USD).
Methods
Untargeted metabolomics was utilized in comparative analyses of calcium-based stones
(CBS) and spot urine samples from patients with a history of USD with or without urinary
stone activity based on radiologic imaging. Stone and urine metabolomes were stratified
by composition and radiographic stone-activity, respectively. Additionally, we quantified
highly abundant metabolites that were present in either calcium oxalate (CaOx) or
calcium phosphate (CaPhos) stones and also significantly enriched in the urine of
active stone formers (SF) compared to non-active SF. These data were used to delineate
either a direct involvement of urinary metabolites in lithogenesis or the passive
uptake of biomolecules within the stone matrix.
Results
Urinary metabolomes were distinct based on radiographic stone-activity and the 2 types
of CBS. Stratification by radiologic stone activity was driven by the enrichment of
14 metabolites in the urine of active SF that were also highly abundant in both CaOx
and CaPhos stones, indicative of a potential involvement of these metabolites in lithogenesis.
Using the combination of these 14 metabolites in total, we generated a model that
correctly classified patients as either active vs non-active SF in a prospectively
recruited cohort with 73% success.
Conclusion
Collectively, our data suggest specific urinary metabolites directly contribute to
the formation of urinary stones and that active SF may excrete higher levels of lithogenic
metabolites than non-active patients. Future studies are needed to confirm these findings
and establish the causative mechanisms associated with these metabolites.
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Article info
Publication history
Published online: June 15, 2022
Accepted:
June 5,
2022
Received:
November 23,
2021
Footnotes
Financial Disclosure: The authors declare no competing interests.
Funding Support: This study was funded with seed funds from Lerner Research Institute and grants from the Research Program Committee at The Cleveland Clinic Foundation and the Urology Care Foundation Research Scholar Award.
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