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Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization
Li Jiang, Jie Jian, Xulin Sai, Xiai Wu
Received May 5, 2024  Accepted September 7, 2024  Published online January 24, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0233    [Epub ahead of print]
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  • 160 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Diabetic kidney disease (DKD) is recognized as a significant complication of diabetes mellitus and categorized into glomerular DKDs and tubular DKDs, each governed by distinct pathological mechanisms and biomarkers.
Methods
Through the identification of common features observed in glomerular and tubular lesions in DKD, numerous differentially expressed gene were identified by the machine learning, single-cell transcriptome and mendelian randomization.
Results
The diagnostic markers versican (VCAN) was identified, offering supplementary options for clinical diagnosis. VCAN significantly highly expressed in glomerular parietal epithelial cell and proximal convoluted tubular cell. It was mainly involved in the up-regulation of immune genes and infiltration of immune cells like mast cell. Mendelian randomization analysis confirmed that serum VCAN protein levels were a risky factor for DKD, while there was no reverse association. It exhibited the good diagnostic potential for estimated glomerular filtration rate and proteinuria in DKD.
Conclusion
VCAN showed the prospects into DKD pathology and clinical indicator.
Complications
Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease
Ji Hye Huh, Minyoung Lee, So Young Park, Jae Hyeon Kim, Byung-Wan Lee
Diabetes Metab J. 2018;42(3):215-223.   Published online May 2, 2018
DOI: https://doi.org/10.4093/dmj.2017.0091
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  • 59 Download
  • 10 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   
Background

The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).

Methods

We classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.

Results

Subjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).

Conclusion

GA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

Citations

Citations to this article as recorded by  
  • Glucagon-Like Peptide 1 Receptor Agonist Improves Renal Tubular Damage in Mice with Diabetic Kidney Disease
    Ran Li, Dunmin She, Zhengqin Ye, Ping Fang, Guannan Zong, Yong Zhao, Kerong Hu, Liya Zhang, Sha Lei, Keqin Zhang, Ying Xue
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 1331.     CrossRef
  • Use of glycated albumin for the identification of diabetes in subjects from northeast China
    Guo-Yan Li, Hao-Yu Li, Qiang Li
    World Journal of Diabetes.2021; 12(2): 149.     CrossRef
  • Diabetic Kidney Disease, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease: A New Triumvirate?
    Carolina M. Perdomo, Nuria Garcia-Fernandez, Javier Escalada
    Journal of Clinical Medicine.2021; 10(9): 2040.     CrossRef
  • Empagliflozin reduces high glucose-induced oxidative stress and miR-21-dependent TRAF3IP2 induction and RECK suppression, and inhibits human renal proximal tubular epithelial cell migration and epithelial-to-mesenchymal transition
    Nitin A. Das, Andrea J. Carpenter, Anthony Belenchia, Annayya R. Aroor, Makoto Noda, Ulrich Siebenlist, Bysani Chandrasekar, Vincent G. DeMarco
    Cellular Signalling.2020; 68: 109506.     CrossRef
  • Glycated Plasma Proteins as More Sensitive Markers for Glycemic Control in Type 1 Diabetes
    Lina Zhang, Qibin Zhang
    PROTEOMICS – Clinical Applications.2020;[Epub]     CrossRef
  • Glycated albumin and its variability: Clinical significance, research progress and overall review
    Dongjun Dai, Yifei Mo, Jian Zhou
    Obesity Medicine.2020; 19: 100256.     CrossRef
  • Hepatic fibrosis is associated with total proteinuria in Korean patients with type 2 diabetes
    Eugene Han, Yongin Cho, Kyung-won Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-wan Lee
    Medicine.2020; 99(33): e21038.     CrossRef
  • Increasing waist circumference is associated with decreased levels of glycated albumin
    Yiting Xu, Xiaojing Ma, Yun Shen, Yufei Wang, Jian Zhou, Yuqian Bao
    Clinica Chimica Acta.2019; 495: 118.     CrossRef
  • Glucometabolic characteristics and higher vascular complication risk in Korean patients with type 2 diabetes with non-albumin proteinuria
    Yongin Cho, Yong-ho Lee, Eun Seok Kang, Bong-soo Cha, Byung-wan Lee
    Journal of Diabetes and its Complications.2019; 33(8): 585.     CrossRef
  • Association of urinary acidification function with the progression of diabetic kidney disease in patients with type 2 diabetes
    Huanhuan Zhu, Xi Liu, Chengning Zhang, Qing Li, Xiaofei An, Simeng Liu, Lin Wu, Bo Zhang, Yanggang Yuan, Changying Xing
    Journal of Diabetes and its Complications.2019; 33(11): 107419.     CrossRef

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