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Abstract: TH-PO886

Alteration of Tryptophan-Kynurenine Metabolites in the Serum and Kidney in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Matsushita, Shoko, Fujita Health University, Toyoake, Japan
  • Takahashi, Kazuo, Fujita Health University, Toyoake, Japan
  • Umeda, Ryosuke, Fujita Health University, Toyoake, Japan
  • Tsuboi, Naotake, Fujita Health University, Toyoake, Japan
  • Nakajima, Kazuki, Fujita Health University, Toyoake, Japan
  • Yoshimura, Aya, Fujita Health University, Toyoake, Japan
  • Kumamoto, Kanako, Fujita Health University, Toyoake, Japan
  • Kugita, Masanori, Fujita Health University, Toyoake, Japan
  • Fujigaki, Hidetsugu, Fujita Health University, Toyoake, Japan
  • Mouri, Akihiro, Fujita Health University, Toyoake, Japan
  • Yamamoto, Yasuko, Fujita Health University, Toyoake, Japan
  • Nabeshima, Toshitaka, Fujita Health University, Toyoake, Japan
  • Setou, Mitsutoshi, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Nagao, Shizuko, Fujita Health University, Toyoake, Japan
  • Saito, Kuniaki, Fujita Health University, Toyoake, Japan
  • Yuzawa, Yukio, Fujita Health University, Toyoake, Japan
Background

It has recently been suggested that several metabolic pathways associated with diabetes interact to influence systemic metabolism, humoral response, and chronic inflammation, contributing to complications of diabetes. Tryptophan-kynurenine (TRP-KYN) metabolites play a vital role in several physiological and pathological conditions including diabetes. However, the contribution of TRP-KYN metabolites to the pathogenesis of diabetic nephropathy has not been established. Metabolomic data analysis was used to detect pathways of systemic interaction associated with the pathogenesis of diabetic nephropathy. We identified that TRP-KYN metabolism was one such pathway that contributed to the progression of diabetic nephropathy.

Methods

To identify TRP-KYN metabolites associated with diabetic nephropathy, we analyzed serum, urine, and tissue levels of TRP-KYN metabolites in an animal model of diabetic nephropathy using uni-nephrectomized spontaneously diabetic Torii fatty rats on 0.3% salt supplementation. Distributions of TRP-KYN metabolites in the kidney were analyzed using matrix-assisted laser desorption/ionization imaging mass spectrometry. Finally, we identified serum TRP-KYN metabolites in patients with diabetic nephropathy proved by renal biopsy.

Results

Profiling of TRP-KYN metabolites in an animal model of diabetic nephropathy revealed activation of the KYN pathway and accumulation of metabolites in kidney tissues. Changes in levels of TRP-KYN metabolites were also observed in patients with diabetic nephropathy. Additionally, the concentration of some metabolites was related to the severity of proteinuria, percentage of glomerular sclerosis, and grade of interstitial cellular infiltration.

Conclusion

Changes in the profile of TRP-KYN metabolites were observed both in animal models and humans with diabetic nephropathy. The concentrations of TRP-KYN metabolites may be associated with the progression of diabetic nephropathy.

Funding

  • Government Support - Non-U.S.