Nontargeted Urine Metabolomics with Electrospray Ionization-Mass Spectrometry Reveals the Major Metabolic Characterization between Adult Males and Females Involved in Calcium Oxalate Urolithiasis

Abstract

The incidence of calcium oxalate (CaOx) urolithiasis between men and women is considerably different. However, the full-scale metabolic changes between genders with CaOx urolithiasis have not been reported. The metabolic profiles in 112 urine samples obtained from 61 males and 51 females diagnosed with CaOx stones were characterized using electrospray ionization-mass spectrometry (ESI-MS). Univariate, multivariate, and bioinformatic analyses were employed to reveal the differential metabolites and perturbed metabolic pathways between genders. In total, 30 dysregulated metabolites were identified as differential metabolites between males and females with CaOx urolithiasis. The primary metabolic pathways were caffeine metabolism, metabolic pathways, and biosynthesis of amino acids. Furthermore, 10 potential metabolites which were mostly contributed to separating the males and female were selected using feature weight calculation. These compounds included creatinine, 3-methylhistidine, n-acetylneuraminic acid, decanoyl-l-carnitine, cortisone, nicotine, 1-methyluric acid, androsterone sulfate, citramalic acid, and 1,7-dimethylxanthine. Finally, a subset of the differential metabolites was identified by receiver operating characteristic (ROC) curve analysis, including creatinine, 3-methylhistidine, n-acetylneuraminic acid, decanoyl-l-carnitine, and 1-methyluric acid (area under the curve = 0.924, 0.844, 0.846, 0.814, 0.814). These metabolites had higher risks in the CaOx stone formation of males than females. The study showed that there were a group of differential metabolites between the males and females with CaOx stones. A subset of these compounds was more closely and positively related to renal stone formation in males than females. Moreover, these metabolites may be the cause of the differences in the incidence of CaOx urolithiasis between genders.

Keywords:

• Calcium oxalate
• electrospray ionization – mass spectrometry (ESI-MS)
• gender
• orthogonal/partial least squares discriminant analysis (OPLS-DA)
• urolithiasis

Acknowledgments

We thank the altruistic support of the patients.

Disclosure statement

The authors have no conflicts of interest.

Data availability statement

All data are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (grant number 82070725), the Science and Technology Project of Tianjin (grant number 21JCYBJC01300), Tianjin Health Research Project (grant number TJWJ2022ZD004), and the Fund of The Second Hospital of Tianjin Medical University (grant number 2023ZDSYS03 and 2022ydey04).