Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy

Akiyoshi Hirayama, Eitaro Nakashima, Masahiro Sugimoto, Shin Ichi Akiyama, Waichi Sato, Shoichi Maruyama, Seiichi Matsuo, Masaru Tomita, Yukio Yuzawa, Tomoyoshi Soga

Research output: Contribution to journalArticle

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Abstract

Capillary electrophoresis coupled with time-offlight mass spectrometry was used to explore new serum biomarkers with high sensitivity and specificity for diabetic nephropathy (DN) diagnosis, through comprehensive analysis of serum metabolites with 78 diabetic patients. Multivariate analyses were used for identification of marker candidates and development of discriminative models. Of the 289 profiled metabolites, orthogonal partial leastsquares discriminant analysis identified 19 metabolites that could distinguish between DN with macroalbuminuria and diabetic patients without albuminuria. These identified metabolites included creatinine, aspartic acid, γ-butyrobetaine, citrulline, symmetric dimethylarginine (SDMA), kynurenine, azelaic acid, and galactaric acid. Significant correlations between all these metabolites and urinary albumin-to-creatinine ratios (p<0.009, Spearman's rank test) were observed. When five metabolites (including γ-butyrobetaine, SDMA, azelaic acid and two unknowns) were selected from 19 metabolites and applied for multiple logistic regressionmodel, AUC value for diagnosing DN was 0.927 using the whole dataset, and 0.880 in a cross-validation test. In addition, when four known metabolites (aspartic acid, SDMA, azelaic acid and galactaric acid) were applied, the resulting AUC was still high at 0.844 with the whole dataset and 0.792 with cross-validation. Combination of serum metabolomics with multivariate analyses enabled accurate discrimination of DN patients. The results suggest that capillary electrophoresis-mass spectrometry based metabolome analysis could be used for DN diagnosis.

Original languageEnglish
Pages (from-to)3101-3109
Number of pages9
JournalAnalytical and Bioanalytical Chemistry
Volume404
Issue number10
DOIs
Publication statusPublished - 01-12-2012
Externally publishedYes

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Diabetic Nephropathies
Biomarkers
Metabolites
Serum
Capillary Electrophoresis
Aspartic Acid
Area Under Curve
Mass Spectrometry
Creatinine
Capillary electrophoresis
Multivariate Analysis
Kynurenine
Citrulline
Albuminuria
Metabolomics
Metabolome
Mass spectrometry
Discriminant Analysis
Albumins
Discriminant analysis

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry

Cite this

Hirayama, A., Nakashima, E., Sugimoto, M., Akiyama, S. I., Sato, W., Maruyama, S., ... Soga, T. (2012). Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. Analytical and Bioanalytical Chemistry, 404(10), 3101-3109. https://doi.org/10.1007/s00216-012-6412-x
Hirayama, Akiyoshi ; Nakashima, Eitaro ; Sugimoto, Masahiro ; Akiyama, Shin Ichi ; Sato, Waichi ; Maruyama, Shoichi ; Matsuo, Seiichi ; Tomita, Masaru ; Yuzawa, Yukio ; Soga, Tomoyoshi. / Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. In: Analytical and Bioanalytical Chemistry. 2012 ; Vol. 404, No. 10. pp. 3101-3109.
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Hirayama, A, Nakashima, E, Sugimoto, M, Akiyama, SI, Sato, W, Maruyama, S, Matsuo, S, Tomita, M, Yuzawa, Y & Soga, T 2012, 'Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy', Analytical and Bioanalytical Chemistry, vol. 404, no. 10, pp. 3101-3109. https://doi.org/10.1007/s00216-012-6412-x

Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy. / Hirayama, Akiyoshi; Nakashima, Eitaro; Sugimoto, Masahiro; Akiyama, Shin Ichi; Sato, Waichi; Maruyama, Shoichi; Matsuo, Seiichi; Tomita, Masaru; Yuzawa, Yukio; Soga, Tomoyoshi.

In: Analytical and Bioanalytical Chemistry, Vol. 404, No. 10, 01.12.2012, p. 3101-3109.

Research output: Contribution to journalArticle

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T1 - Metabolic profiling reveals new serum biomarkers for differentiating diabetic nephropathy

AU - Hirayama, Akiyoshi

AU - Nakashima, Eitaro

AU - Sugimoto, Masahiro

AU - Akiyama, Shin Ichi

AU - Sato, Waichi

AU - Maruyama, Shoichi

AU - Matsuo, Seiichi

AU - Tomita, Masaru

AU - Yuzawa, Yukio

AU - Soga, Tomoyoshi

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