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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.

Author(s): Fedrigon, Donald; Alshara, Luay; Monga, Manoj | Abstract: INTRODUCTION:Two automated irrigation systems have been released for use during endoscopic procedures such as ureteroscopy: the Cogentix RocaFlow® (CRF) and Thermedx FluidSmart® (TFS). Accurate pressure control using automated systems may help providers maintain irrigation pressures within a safe range while also providing clear visualization. Our objective was to directly compare these systems based on their pressure accuracy, pressure-flow relationships, and fluid heating capabilities in order to help providers better utilize the temperature and pressure settings of each system. MATERIALS AND METHODS:An in vitro ureteroscopy model was used for testing, consisting of a short semirigid ureteroscope (6/7, 5F, 31cm Wolf 425612) connected to a continuous digital pressure transducer (Meriam m1550). Each system pressure output and flow-rate, via 100mL beaker filling time, was measured using multiple trials at pressure settings between 30 and 300mmHg. Output fluid temperature was monitored using a digital thermometer (Omega DP25-TH). RESULTS:The pressure output of both systems exceeded the desired setting across the entire tested range, a difference of 15.7±2.4mmHg for the TFS compared to 5.2±1.5mmHg for the CRF (p l 0.0001). Related to this finding, the TFS also had slightly higher flow rates across all trials (7±2mL/min). Temperature testing revealed a similar maximum temperature of 34.0⁰C with both systems, however, the TFS peaked after only 8 minutes and started to plateau as early as 4-5 minutes into the test, while the CRF took over 18 minutes to reach a similar peak. CONCLUSIONS:Our in vitro ureteroscopy testing found that the CRF system had better pressure accuracy than the TFS system but with noticeably slower fluid heating capabilities. Each system provided steady irrigation at safe pressures within their expected operating parameters with small differences in performance that should not limit their ability to provide steady irrigation at safe pressures.