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Updated: Aug 5, 2025

Identification and Quantification of Deranged Metabolites in Critically Ill Patients Using NMR-Based Metabolomics
Published on: November 29, 2024
Untargeted plasma 1H NMR-based metabolomic profiling in different stages of chronic kidney disease
Renato Itamar Duarte Fonseca1, Leociley Rocha Alencar Menezes2, Arquimedes Paixão Santana-Filho2
1Department of Basic Pathology, Universidade Federal do Paraná, Curitiba 80050-540, Brazil.
Insights
Nuclear Magnetic Resonance Spectroscopy (NMR) identified distinct metabolic profiles in chronic kidney disease (CKD) patients. These changes, including specific metabolites, can help track disease progression and inform treatment strategies.
Area of Science:
- Biochemistry
- Metabolomics
- Nephrology
Background:
- Chronic kidney disease (CKD) is a global health concern.
- Current diagnostic methods like eGFR and albuminuria offer limited insight into CKD progression mechanisms.
- Understanding CKD's metabolic underpinnings is crucial for improved management.
Purpose of the Study:
- To identify specific changes in plasma metabolomic profiles associated with advancing stages of chronic kidney disease (CKD).
- To explore the potential of Nuclear Magnetic Resonance (NMR) spectroscopy for metabolic assessment in CKD patients.
Main Methods:
- Analyzed 77 plasma samples from CKD patients and controls using 1D and 2D NMR spectroscopy.
- Employed Principal Component Analysis (PCA) for data clustering and identification of discriminating metabolites.
- Utilized MetaboAnalyst 4.0 for pathway analysis on CKD stage 5 (G5) plasma samples.
Main Results:
- Significant differences in metabolomic profiles were observed between CKD patients and controls.
- PCA successfully clustered patients into control, early-to-mid stage CKD (G1-G4), and late-stage CKD (G5) groups.
- Specific metabolites like lactate, glucose, acetate, and creatinine differentiated CKD stages, while TMAO generation was highlighted in G5.
Conclusions:
- NMR-based metabolomic profiling can effectively distinguish between different stages of CKD.
- Metabolic pathway analysis revealed key pathways, including glycolysis and gluconeogenesis, involved in CKD.
- The findings support the feasibility of using NMR for monitoring CKD progression and treatment response.
Abstract:
Chronic kidney disease (CKD) is a serious public health issue affecting thousands of people worldwide. CKD diagnosis is usually made by Estimated Glomerular Filtration Rate (eGFR) and albuminuria, which limit the knowledge of the mechanisms behind CKD progression. The aim of the present study was to identify changes in the metabolomic profile that occur as CKD advances. In this sense, 77 plasma samples from patients with CDK were evaluated by 1D and 2D Nuclear Magnetic Resonance Spectroscopy (NMR). The NMR data showed significant changes in the metabolomic profile of CKD patients and the control group. Principal component analysis (PCA) clustered CKD and control patients into three distinct groups, control, stage 1 (G1)-stage 4 (G4) and stage 5 (G5). Lactate, glucose, acetate and creatinine were responsible for discriminating the control group from all the others CKD stages. Valine, alanine, glucose, creatinine, glutamate and lactate were responsible for the clustering of G1-G4 stages. G5 was discriminated by calcium ethylenediamine tetraacetic acid, magnesium ethylenediamine tetraacetic acid, creatinine, betaine/choline/trimethylamine N-oxide (TMAO), lactate and acetate. CKD G5 plasma pool which was submitted in MetaboAnalyst 4.0 platform (MetPA) analysis and showed 13 metabolic pathways involved in CKD physiopathology. Metabolic changes associated with glycolysis and gluconeogenesis allowed discriminating between CKD and control patients. The determination of involved molecules in TMAO generation in G5 suggests an important role in this uremic toxin linked to CKD and cardiovascular diseases. The aforementioned results propose the feasibility of metabolic assessment of CKD by NMR during treatment and disease progression.
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