Kidney Week

Abstract: SA-PO614

Systematic Metabolomics Study in the Serum and Urine of a Mouse Model of Alport Syndrome

Session Information

• Genetic Kidney Diseases: Models, Mechanisms, and Therapies
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Choi, Hong Sang, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)

Hong Sang Choi, MD, PhD

• Suh, Sang Heon, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)

Sang Heon Suh, MD, PhD

• Kim, Chang Seong, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)

Chang Seong Kim, MD, PhD

• Bae, Eun Hui, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)

Eun Hui Bae, MD, PhD

• Ma, Seong Kwon, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)

Seong Kwon Ma, MD, PhD

• Kim, Soo Wan, Chonnam National University Medical School, Gwangju, Gwangju, Korea (the Republic of)

Soo Wan Kim, MD, PhD

Background

Alport syndrome (AS) is a hereditary nephropathy characterized by progressive kidney disease and hearing loss, which is caused by mutations in the genes encoding the alpha 3, 4, or 5 chain comprising the type IV collagen that forms glomerular basement membrane. There is a limited understanding of the metabolites related to progressive kidney disease in AS.

Methods

Metabolomics study was performed for monitoring of biomarker and altered metabolism related with disease progression in serum and urine from male Col4a3 knockout mice and age-matched wild-type mice at 4 and 7 weeks. Profiling analysis for metabolites, including organic acids, amino acids, fatty acids, kynurenine pathway metabolites, and nucleosides in the serum and urine was performed using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry combined with star symbol patterns and partial least squares discriminant analysis (PLS-DA).

Results

A total of 29 and 44 metabolites from the serum and urine of Col4a3^-/- mice were distinguished from those of wild-type mice, respectively, based on P-value (< 0.05) and variable importance in projection scores (> 1.0) of PLS-DA. In the serum of 4 weeks AS mice, metabolites of the glycolysis, gluconeogenesis, pyruvate metabolism and TCA cycle were increased, whereas those involved in alanine, aspartate and glutamate metabolism, arginine and proline metabolism, arginine biosynthesis and D-glutamine and D-glutamate metabolism were altered in serum of 7 weeks AS mice.

Conclusion

Altered metabolic pathway and metabolites are associated with progressive kidney disease in AS.