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Review
. 2021 May 11;21(7):21.
doi: 10.1007/s11892-021-01390-8.

Harnessing Metabolomics to Describe the Pathophysiology Underlying Progression in Diabetic Kidney Disease

Sho Hasegawa  1   2 , Reiko Inagi  3
Affiliations
Review

Harnessing Metabolomics to Describe the Pathophysiology Underlying Progression in Diabetic Kidney Disease

Sho Hasegawa et al. Curr Diab Rep. .

Abstract

Purpose of review: Diabetic kidney disease (DKD), a leading cause of end-stage kidney disease, is the result of metabolic network alterations in the kidney. Therefore, metabolomics is an effective tool for understanding its pathophysiology, finding key biomarkers, and developing a new treatment strategy. In this review, we summarize the application of metabolomics to DKD research.

Recent findings: Alterations in renal energy metabolism including the accumulation of tricarboxylic acid cycle and glucose metabolites are observed in the early stage of DKD, and they finally lead to mitochondrial dysfunction in advanced DKD. Mitochondrial fission-fusion imbalance and dysregulated organelle crosstalk might contribute to this process. Moreover, metabolomics has identified several uremic toxins including phenyl sulfate and tryptophan derivatives as promising biomarkers that mediate DKD progression. Recent advances in metabolomics have clarified the role of dysregulated energy metabolism and uremic toxins in DKD pathophysiology. Integration of multi-omics data will provide additional information for identifying critical drivers of DKD.

Keywords: Biomarker; Diabetic kidney disease; Metabolomics; Mitochondria; Organelle crosstalk; Uremic toxin.

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Figures

Fig. 1.
Fig. 1.
Dysregulated energy metabolism and mitochondrial dysfunction in diabetic kidney disease (DKD). In the early stage of DKD, TCA cycle and glucose metabolites are accumulated in renal tissues. The metabolic burden induces the imbalance of mitochondrial fission-fusion and dysregulated crosstalk between ER and mitochondria through MAMs, which finally leads to mitochondrial dysfunction in the late stage of DKD. TCA cycle, tricarboxylic acid cycle; ETC, the electron transport chain; ER, endoplasmic reticulum; MAM, mitochondria-associated membrane
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