Comparative analysis of therapeutic effects between medium cut-off and high flux dialyzers using metabolomics and proteomics: exploratory, prospective study in ... View Full Text


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Article Info

DATE

2021-08-30

AUTHORS

Hyo Jin Kim, Eun Young Seong, Wonho Lee, Suhkmann Kim, Hee-Sung Ahn, Jeonghun Yeom, Kyunggon Kim, Chae Hwa Kwon, Sang Heon Song

ABSTRACT

In this single-center prospective study of 20 patients receiving maintenance hemodialysis (HD), we compared the therapeutic effects of medium cut-off (MCO) and high flux (HF) dialyzers using metabolomics and proteomics. A consecutive dialyzer membrane was used for 15-week study periods: 1st HF dialyzer, MCO dialyzer, 2nd HF dialyzer, for 5 weeks respectively. 1H-nuclear magnetic resonance was used to identify the metabolites and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was used to identify proteins. To compare the effects of the HF and MCO dialyzers, orthogonal projection to latent structure discriminant analysis (OPLS-DA) was performed. OPLS-DA showed that metabolite characteristics could be significantly classified by 1st HF and MCO dialyzers. The Pre-HD metabolites with variable importance in projection scores ≥ 1.0 in both 1st HF versus MCO and MCO versus 2nd HF were succinate, glutamate, and histidine. The pre-HD levels of succinate and histidine were significantly lower, while those of glutamate were significantly higher in MCO period than in the HF period. OPLS-DA of the proteome also substantially separated 1st HF and MCO periods. Plasma pre-HD levels of fibronectin 1 were significantly higher, and those of complement component 4B and retinol-binding protein 4 were significantly lower in MCO than in the 1st HF period. Interestingly, as per Ingenuity Pathway Analysis, an increase in epithelial cell proliferation and a decrease in endothelial cell apoptosis occurred during the MCO period. Overall, our results suggest that the use of MCO dialyzers results in characteristic metabolomics and proteomics profiles during HD compared with HF dialyzers, which might be related to oxidative stress, insulin resistance, complement-coagulation axis, inflammation, and nutrition. More... »

PAGES

17335

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-021-96974-5

DOI

http://dx.doi.org/10.1038/s41598-021-96974-5

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34462546


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36 schema:description In this single-center prospective study of 20 patients receiving maintenance hemodialysis (HD), we compared the therapeutic effects of medium cut-off (MCO) and high flux (HF) dialyzers using metabolomics and proteomics. A consecutive dialyzer membrane was used for 15-week study periods: 1st HF dialyzer, MCO dialyzer, 2nd HF dialyzer, for 5 weeks respectively. 1H-nuclear magnetic resonance was used to identify the metabolites and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was used to identify proteins. To compare the effects of the HF and MCO dialyzers, orthogonal projection to latent structure discriminant analysis (OPLS-DA) was performed. OPLS-DA showed that metabolite characteristics could be significantly classified by 1st HF and MCO dialyzers. The Pre-HD metabolites with variable importance in projection scores ≥ 1.0 in both 1st HF versus MCO and MCO versus 2nd HF were succinate, glutamate, and histidine. The pre-HD levels of succinate and histidine were significantly lower, while those of glutamate were significantly higher in MCO period than in the HF period. OPLS-DA of the proteome also substantially separated 1st HF and MCO periods. Plasma pre-HD levels of fibronectin 1 were significantly higher, and those of complement component 4B and retinol-binding protein 4 were significantly lower in MCO than in the 1st HF period. Interestingly, as per Ingenuity Pathway Analysis, an increase in epithelial cell proliferation and a decrease in endothelial cell apoptosis occurred during the MCO period. Overall, our results suggest that the use of MCO dialyzers results in characteristic metabolomics and proteomics profiles during HD compared with HF dialyzers, which might be related to oxidative stress, insulin resistance, complement-coagulation axis, inflammation, and nutrition.
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44 HF dialyzers
45 HF period
46 Ingenuity Pathway Analysis
47 MCO
48 MCO dialyzer
49 MCO period
50 OPLS-DA
51 analysis
52 apoptosis
53 axis
54 cell apoptosis
55 cell proliferation
56 characteristics
57 comparative analysis
58 complement component 4B
59 cut
60 decrease
61 dialyzer
62 dialyzer membranes
63 discriminant analysis
64 effect
65 endothelial cell apoptosis
66 epithelial cell proliferation
67 fibronectin 1
68 flux dialyzers
69 glutamate
70 hemodialysis
71 high-flux dialyzers
72 histidine
73 importance
74 increase
75 inflammation
76 insulin resistance
77 latent structures discriminant analysis
78 levels
79 liquid chromatography-tandem mass spectrometry analysis
80 magnetic resonance
81 maintenance hemodialysis
82 mass spectrometry analysis
83 medium cut
84 membrane
85 metabolites
86 metabolites characteristic
87 metabolomics
88 nutrition
89 orthogonal projection
90 oxidative stress
91 pathway analysis
92 patients
93 period
94 pre-HD levels
95 profile
96 projection scores
97 projections
98 proliferation
99 prospective study
100 protein
101 protein 4
102 proteome
103 proteomic profiles
104 proteomics
105 resistance
106 resonance
107 results
108 retinol-binding protein 4
109 scores
110 single-center prospective study
111 spectrometry analysis
112 stress
113 study
114 study period
115 succinate
116 therapeutic effect
117 use
118 variable importance
119 weeks
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