DOI: 10.3390/metabo16100711 ISSN: 2218-1989

Linking Stone Mineral Composition to 24-Hour Urinary Metabolic Profiles: An Episode-Based Cohort Study

Shiwei Sun, Jiang Liu, Yi Qiao, Dong Wang, Lin Ma, Hongjun Li, He Xiao

Background/Objectives: Stone composition reflects the urinary environment in which calculi form, whereas 24 h urine testing identifies modifiable lithogenic abnormalities. This study examined component-specific urinary metabolic profiles and evaluated whether routine clinical and urinary variables could distinguish common stone minerals. Methods: This retrospective study included 256 patients undergoing 297 stone surgeries, consolidated into 256 treatment episodes. Fourier-transform infrared spectroscopy identified stone minerals, which were linked to preoperative 24 h urine profiles. Calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), carbonate apatite, and anhydrous uric acid were evaluated using multivariable logistic regression. Mutually exclusive calcium oxalate–calcium phosphate phenotypes, nested cross-validated prediction models, and unsupervised clustering were also examined. Results: COM, COD, carbonate apatite, and anhydrous uric acid were present in 78.5%, 73.0%, 39.5%, and 9.8% of episodes, respectively. Higher urine pH was associated with carbonate apatite (odds ratio [OR] per standard deviation, 1.78; 95% confidence interval [CI], 1.33–2.38), whereas lower pH was associated with anhydrous uric acid (OR, 0.26; 95% CI, 0.11–0.58). Higher urinary citrate was associated with COM, but phenotype analysis showed that hypocitraturia increased from 45.3% in calcium oxalate-only episodes to 60.7% in mixed calcium oxalate–calcium phosphate episodes and 89.5% in calcium phosphate episodes without calcium oxalate. Lower urine volume was associated with COD. Cross-validated areas under the curve ranged from 0.654 to 0.712, and metabolic clusters showed substantial mineral overlap. Conclusions: Urine pH provided the clearest component-specific signal, whereas citrate associations depended on accompanying minerals. Routine 24 h urine testing complemented but did not replace direct stone analysis.