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Abstract: SA-PO650

Metabolomics Reveals Serum mTOR Signaling Activation in IgA Nephropathy Patients

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Kim, Hyung Woo, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
  • Park, Tae-Joon, Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea (the Republic of)
  • Kong, Jinhwa, Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea (the Republic of)
  • Nam, Boyoung, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
  • Han, Seung Hyeok, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
  • Yoo, Tae-Hyun, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
  • Kang, Shin-Wook, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
  • Kim, Bong-Jo, Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea (the Republic of)
  • Lee, Heun-Sik, Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju, Korea (the Republic of)
  • Park, Jung Tak, Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Korea (the Republic of)
Background

Circulating metabolites are known to play key roles in the pathophysiology of several diseases. In Immunoglobulin A nephropathy (IgAN), the role of systemic milieu as a risk factor for progression has been reported. However, the serum metabolic profile of IgAN and its role in disease progression is not well known.

Methods

Twenty-five patients with IgAN and five controls without IgAN were included in this study. The capillary electrophoresis and time-of-flight mass spectrometry-based metabolomics quantification was applied for the serum metabolic profile. The concentration of each metabolite was log-transformed and scaled. To determine metabolomic differences between IgAN and controls, a principle components analysis (PCA), hierarchical cluster analysis (HCA), and univariate Welch’s t-test was performed. Metabolite pathway analysis was performed to find significant disease-pathway associations. Pathway sets were obtained from the Kyoto Encyclopedia of Genes and Genomes and the Ingenuity Pathway Analysis (IPA) database.

Results

The mean age of the patients with IgAN was 39.4 years, and 44% were female. The mean eGFR was 89.7 ± 27.6 ml/min per 1.73 m2 and the median urine protein-to-creatinine ratio was 1.5 [0.9 to 2.8] g/g. The mean age of controls was 55.6 years, and 80% were female. The mean eGFR was 84.7 ± 11.4 ml/min per 1.73 m2. A total 56 serum metabolites were assessed. PCA and HCA revealed significant metabolic pathway differences between IgAN and controls. Welch’s t-test showed that 16 metabolites (3 and 13 metabolites in the anion and cation, respectively) concentrations were significantly higher in IgAN patients after multiple test correction. Pathway enrichment analysis showed that four pathways were associated with these 16 metabolites: Valine, leucine and isoleucine degradation, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, and alanine, aspartate and glutamate metabolism. In addition, IPA database revealed mTOR signaling pathway to be related with the 4 metabolites among 16 metabolites.

Conclusion

In this metabolomics analysis, 16 metabolites were noticed as those that significantly identify IgAN. The mTOR signaling pathway activation through these metabolites may play a role in IgAN pathophysiology.

Funding

  • Government Support – Non-U.S.