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Original Article Complications Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus
Inha Jung1orcid , Seungyoon Nam2,3, Da Young Lee1, So Young Park1, Ji Hee Yu1, Ji A Seo1, Dae Ho Lee3,4orcid , Nan Hee Kim1orcid

DOI: https://doi.org/10.4093/dmj.2023.0377 [Epub ahead of print]
Published online: July 1, 2024
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1Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
2Department of Genome Medicine and Science, AI Convergence Center for Medical Science, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
3Department of Health Sciences and Technology, Gachon Advanced Institute for Health Sciences and Technology, Gachon University, Incheon, Korea
4Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
Corresponding author:  Dae Ho Lee,
Email: drhormone@naver.com
Nan Hee Kim,
Email: nhkendo@gmail.com
Received: 23 October 2023   • Accepted: 6 May 2024

Background
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
Methods
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
Results
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
Conclusion
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

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Jung I, Nam S, Lee DY, Park SY, Yu JH, Seo JA, Lee DH, Kim NH. Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus. Diabetes Metab J. 2024 Jul 1. doi: 10.4093/dmj.2023.0377. Epub ahead of print.
Received: Oct 23, 2023; Accepted: May 06, 2024
DOI: https://doi.org/10.4093/dmj.2023.0377.

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