To delineate the role of the urinary metabolome in the genesis of urinary stone disease (USD).
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.
Urinary metabolomes were distinct based on radiographic stone-activity and the two 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.
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.
Urology. 2022 Jun 15 [Epub ahead of print]
Jose Agudelo, Donald Fedrigon, Anna Faris, Lamont Wilkins, Manoj Monga, Aaron W Miller
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA., Department of Urology, Emory University, Atlanta GA, USA., Department of Urology, University of Michigan, Ann Arbor, MI, USA., Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA., Department of Urology, University of California San Diego, San Diego, CA., Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: .