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. 2020 Jul 16;10(7):291.
doi: 10.3390/metabo10070291.

Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients

Fatin Athirah Pauzi  1 , Sharmela Sahathevan  2 , Ban-Hock Khor  3 , Sreelakshmi Sankara Narayanan  4 , Nor Fadhlina Zakaria  5 , Faridah Abas  6 , Tilakavati Karupaiah  4 , Zulfitri Azuan Mat Daud  1
Affiliations

Exploring Metabolic Signature of Protein Energy Wasting in Hemodialysis Patients

Fatin Athirah Pauzi et al. Metabolites. .

Abstract

End-stage renal disease patients undergoing maintenance hemodialysis (HD) are vulnerable to the protein energy wasting (PEW) syndrome. Identification and diagnosis of PEW relies on clinical processes of judgment dependent on fulfilling multiple criteria drawn from serum biochemistry, weight status, predictive muscle mass, dietary energy and protein intakes. Therefore, we sought to explore the biomarkers' signature with plasma metabolites of PEW by using 1H-nuclear magnetic resonance for an untargeted metabolomics approach in the HD population, to understand metabolic alteration of PEW. In this case-controlled study, a total of 53 patients undergoing chronic HD were identified having PEW based on established diagnostic criteria and were age- and sex-matched with non-PEW (n = 53) HD patients. Fasting predialysis plasma samples were analyzed. Partial least square discriminant analysis demonstrated a significant separation between groups for specific metabolic pattern alterations. Further quantitative analysis showed that the level of 3-hydroxybutyrate, acetate, arabinose, maltose, ribose, sucrose and tartrate were significantly increased whilst creatinine was significantly decreased (all p < 0.05) in PEW subjects. Pathway analysis indicated that PEW-related metabolites reflected perturbations in fatty acid mechanism and induction of glyoxylate and dicarboxylate pathway attributed to gluconeogenesis. These results provide preliminary data in understanding metabolic alteration of PEW and corresponding abnormal metabolites that could potentially serve as biomarkers of PEW.

Keywords: 1H-NMR; hemodialysis; metabolic pathways; metabolomics; plasma metabolites; protein energy wasting.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Characterization of the plasma metabolic changes in PEW and non-PEW hemodialysis (HD) patients. Partial least square-discriminant analysis (PLS-DA) score plot indicating metabolomics profile between the two groups (green = PEW; blue = NPEW) with each score representing one subject. The eclipse represents the 95th percentile of confidence interval, while any score outside of the eclipse is considered an outlier. Nine outlier scores were excluded from the analysis. Metabolomics profile of the two groups was clearly discriminated as indicated by a clear separation trend.
Figure 2
Figure 2
Corresponding loading plot of PLS-DA with a confluence of variable importance in the projection (VIP) results (highlighted as red). The loading plot reveals the important regions in the spectra (metabolites) are responsible for the group clustering shown by the score plot. These regions matched those identified by the VIP plot (VIP > 1) and lead to the separation of the groups.
Figure 3
Figure 3
Proposed metabolic pathways of the PEW condition. The figure shows the correlation network of significantly altered metabolites detected in plasma of PEW group patients. The disordered metabolic pathways are fatty acid β-oxidation and gluconeogenesis. The changes of metabolites in PEW subjects are shown in orange (significantly increased) and blue (significantly decreased) as compared to NPEW groups. * Tartrate significance is diminished after adjustment for covariates.
See this image and copyright information in PMC

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