A metabolomics-based approach for predicting stages of chronic kidney disease

Kobayashi, Toshihiro; T, Yoshida; Fujisawa, Tatsuya; Matsumura, Yukihiko; Ozawa, Toshihiko; Yanai, Hiroyuki; Iwasawa, Atsuo; Kamachi, Toshiaki; Fujiwara, Kazutoshi; Kohno, Masahiro; Tanaka, Noriaki

doi:10.1016/j.bbrc.2014.02.021

Cited by 36 publications

(18 citation statements)

References 17 publications

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“…The work by Rhee et al confirmed that serum levels of kynurenic acid and kynurenine, tryptophan catabolites of the kynurenine pathway, increase with CKD development and severity, as previously had been proposed in a small case-control study including 80 Caucasian individuals [66]. Alterations in the kynurenine pathway have also been associated with decreased eGFR and advanced CKD in several studies conducted in 69 Asian patients [67], Caucasians (two studies, 49 and 80 patients, respectively) [30,66] and 1104 African Americans [68].…”

Section: Metabolomicssupporting

confidence: 52%

Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease

Cañadas-Garre

Anderson

McGoldrick

et al. 2019

Journal of Proteomics

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Section: Metabolomicssupporting

confidence: 52%

Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease

Cañadas-Garre

Anderson

McGoldrick

et al. 2019

Journal of Proteomics

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“…It has been reported that anti-oxidant taurine can ameliorate oxidative stress and inflammation in CKD [48], [51]. Elevated plasma indoxyl sulfate and hippuric acid have been regarded as biomarkers for predicting the stages of CKD [52]. Additionally, other uremia solutes p-cresol and p-cresol sulfate are significantly altered in plasma and urine of CKD patients [5], [53].…”

Section: Discussionmentioning

confidence: 99%

Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease

et al. 2017

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Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques. Compared with healthy controls, patients with CKD showed activation of NF-κB and up-regulation of pro-inflammatory and pro-oxidant mRNA and protein expression as well as down-regulation of Nrf2-associated anti-oxidant gene mRNA and protein expression, accompanied by activated canonical Wnt/β-catenin signaling. 124 plasma and 128 urine metabolites were identified and 40 metabolites were significantly altered in both plasma and urine. Plasma concentration and urine excretion of 25 metabolites were distinctly different between CKD and controls. They were related to amino acid, methylamine, purine and lipid metabolisms. Logistic regression identified four plasma and five urine metabolites. Parts of them were good correlated with eGFR or serum creatinine. 5-Methoxytryptophan and homocystine and citrulline were good correlated with both eGFR and creatinine. Clinical factors were incorporated to establish predictive models. The enhanced metabolite model showed 5-methoxytryptophan, homocystine and citrulline have satisfactory accuracy, sensitivity and specificity for predictive CKD. The dysregulation of CKD was related to amino acid, methylamine, purine and lipid metabolisms. 5-methoxytryptophan, homocystine and citrulline could be considered as additional GFR-associated biomarker candidates and for indicating advanced renal injury. CKD caused dysregulation of the plasma and urine metabolome, activation of inflammatory/oxidative pathway and Wnt/β-catenin signaling and suppression of antioxidant pathway.

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“…Metabolomics has been used to discover the biomarkers, mechanisms, and pathological stages of CKD [8,9] equations from biomarkers were used to predict CKD stages with 81.3 % accuracy [10]. Hankemeier et al applied GC-MS and liquid chromatography-mass spectrometry (LC-MS) to detect potential early indicators of pathological changes, found significant biomarkers, and suggested tryptophan metabolism for further biological studies [11].…”

Section: Introductionmentioning

confidence: 99%

The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods

et al. 2016

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Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-β1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."

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A metabolomics-based approach for predicting stages of chronic kidney disease

Cited by 36 publications

References 17 publications

Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease

Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease

Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt/β-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease

The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods

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