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. 2020 Mar 2:2020:3049098.
doi: 10.1155/2020/3049098. eCollection 2020.

Identification of Potential Serum Metabolic Biomarkers of Diabetic Kidney Disease: A Widely Targeted Metabolomics Study

Affiliations

Identification of Potential Serum Metabolic Biomarkers of Diabetic Kidney Disease: A Widely Targeted Metabolomics Study

Hang Zhang et al. J Diabetes Res. .

Abstract

Background and Objectives. Diabetic kidney disease is a leading cause of chronic kidney disease and end-stage renal disease across the world. Early identification of DKD is vitally important for the effective prevention and control of it. However, the available indicators are doubtful in the early diagnosis of DKD. This study is aimed at determining novel sensitive and specific biomarkers to distinguish DKD from their counterparts effectively based on the widely targeted metabolomics approach. Materials and Method. This case-control study involved 44 T2DM patients. Among them, 24 participants with DKD were defined as the cases and another 20 without DKD were defined as the controls. The ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry system was applied for the assessment of the serum metabolic profiles. Comprehensive analysis of metabolomics characteristics was conducted to detect the candidate metabolic biomarkers and assess their capability and feasibility.

Result: A total of 11 differential metabolites, including Hexadecanoic Acid (C16:0), Linolelaidic Acid (C18:2N6T), Linoleic Acid (C18:2N6C), Trans-4-Hydroxy-L-Proline, 6-Aminocaproic Acid, L-Dihydroorotic Acid, 6-Methylmercaptopurine, Piperidine, Azoxystrobin Acid, Lysopc 20:4, and Cuminaldehyde, were determined as the potential biomarkers for the DKD early identification, based on the multivariable generalized linear regression model and receiver operating characteristic analysis.

Conclusion: Serum metabolites might act as sensitive and specific biomarkers for DKD early detection. Further longitudinal studies are needed to confirm our findings.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1
Typical TIC chromatograms obtained from the same serum sample of a DKD patient with (a) positive and (b) negative mode.
Figure 2
Figure 2
(a) Score plot of the PCA model. (b) Score plot of the OP-LSDA model (R2Xcum = 70%, R2Ycum = 83%, Qcum2 = 56%) showed the separation of the DKD group and non-DKD group. (c) 1000-times permutation test of the model showed that the model had high stability.
Figure 3
Figure 3
(a) Heatmap showed the differences of metabolics between the DKD group and non-DKD group. (b) The pathway analysis showed that Linoleic Acid metabolism, aminoacyl-tRNA biosynthesis, and arginine and proline metabolism are associated with DKD.
Figure 4
Figure 4
Capability and feasibility of single metabolite and combination (Linolelaidic Acid (C18:2N6T), L-Dihydroorotic Acid, and Azoxystrobin Acid) of three screened metabolites models.

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