Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

Park, Sehoon; Lee, Jueun; Yang, Seung Hee; Lee, Hajeong; Kim, Joo Young; Park, Min-Kyoung; Kim, Kyu Hong; Moon, Jiwon; Cho, Semin; Lee, Soojin; Kim, Yaerim; Lee, Jung Pyo; Jeong, Chang Wook; Kwak, Cheol; Joo, Kwon Wook; Lim, Chun Soo; Hwang, Gwi Seo; Kim, Yon Su

doi:10.1111/jcmm.16520

Cited by 17 publications

(20 citation statements)

References 28 publications

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“…However, since it can be assumed to be a derivative of phenylalanine, this suggests the involvement of phenylalanine's metabolism, which is implicated in CKD biochemistry [29]. Park et al propose urinary glycine levels as a potential biomarker for discriminating IgAN patients from patients with MN or other types of glomerulonephritis, however, in our study glycine did not represent any statistical significance in classification [12].…”

Section: Univariate Analysis-biomarker Evaluation On Igan and Mn Disc...contrasting

confidence: 71%

“…Recently two studies target the two most common glomerulonephritis subtypes, providing potential classification models and biomarkers. The studies by Park, Sehoon, et al [12] and Taherkhani, Amir, et al [13] provide the first, comprehensive metabolomic studies of IgAN and primary MN, respectively, providing first insights into the underlying causes of each condition.…”

Section: Introductionmentioning

confidence: 99%

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NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes

et al. 2022

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Chronic Kidney Disease (CKD) is considered as a major public health problem as it can lead to end-stage kidney failure, which requires replacement therapy. A prompt and accurate diagnosis, along with the appropriate treatment, can delay CKD’s progression, significantly. Herein, we sought to determine whether CKD etiology can be reflected in urine metabolomics during its early stage. This is achieved through the analysis of the urine metabolic fingerprint from 108 CKD patients by means of Nuclear Magnetic Resonance (NMR) spectroscopy metabolomic analysis. We report the first NMR—metabolomics data regarding the three most common etiologies of CKD: Chronic Glomerulonephritis (IgA and Membranous Nephropathy), Diabetic Nephropathy (DN) and Hypertensive Nephrosclerosis (HN). Analysis aided a moderate glomerulonephritis clustering, providing characterization of the metabolic fluctuations between the CKD subtypes and control disease. The urine metabolome of IgA Nephropathy reveals a specific metabolism, reflecting its different etiology or origin and is useful for determining the origin of the disease. In contrast, urine metabolomes from DN and HN patients did not reveal any indicative metabolic pattern, which is consistent with their fused clinical phenotype. These findings may contribute to improving diagnostics and prognostic approaches for CKD, as well as improving our understanding of its pathology.

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Section: Univariate Analysis-biomarker Evaluation On Igan and Mn Disc...contrasting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes

et al. 2022

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“…Among them, tryptophan, kynurenine, and ornithine were increased. Metabolic disturbances of amino acids were also observed in another IgAN metabolomics study, in which alanine, glycine, and isoleucine levers were signi cantly up-regulated [20]. Besides, tryptophan was an essential amino acid for an organism's energy metabolism and was a precursor material for 5-hydroxytryptamine and kynurenine [36].…”

Section: Amino Acid Metabolism Of Dams In Igan Plasmamentioning

confidence: 95%

“…In another study, NMR-based metabolomics was applied for the urinary metabolic pro le and could provide a differential diagnosis of primary focal segmental glomerulosclerosis (FSGS) and other glomerulopathies [19]. In IgAN, metabolomic pro ling has found that glycine levels increased without reduced eGFR compared to healthy, membranous nephropathy (MN), minimal change disease (MCD), or lupus nephritis (LN) [20]. However, integrative multi-omics analysis was less applied in IgAN.…”

Section: Introductionmentioning

confidence: 99%

Integrated Proteomics and Metabolomics to Study IgA Nephropathy on Early Stage and Identification of Biomarkers

Zhang

Liang

et al. 2022

Preprint

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Background IgA nephropathy (IgAN) is the most common primary chronic glomerulopathy globally. For IgAN diagnosis, kidney biopsy is still the standard method, which is invasive. And there are no effective plasma biomarkers for the disease at the early stage. The research aimed to find potential biomarkers for diagnosing IgAN. Methods Plasma samples of 33 early-stage IgAN patients who were not taking hormonal drugs and 20 healthy controls were collected for proteomic and metabolomic analysis. The least absolute shrinkage and selection operator (LASSO) was used to construct a binary logistic regression model by combining proteomic and metabolomic data. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, and specificity test were performed to assess the model's performance. Results Proteomic analysis of IgAN plasma revealed that the complement and the immune system were activated. And the metabolomic result showed that energy and amino acid metabolism were disordered in IgAN patients. Through machine learning, PRKAR2A, IL6ST, SOS1, and palmitoleic acid have been identified as potential biomarkers. Based on the AUC value for the training and test sets, the classification performance was 0.994 and 0.977, respectively. The AUC of the external validation of the four biomarkers was 0.91. Conclusion In this study, we applied proteomics and metabolomics techniques to analyze the plasma of IgAN patients and find biomarkers. PRKAR2A, IL6ST, SOS1, and palmitoleic acid were combined to serve as potential biomarkers for early diagnosis of IgAN.

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“…In a study by Zhu et al (24) on mice with acute paraquat poisoning, isoleucine and leucine were found to be significantly negatively correlated with blood creatinine levels (both P<0.05), suggesting a correlation between BCAA metabolism and renal function. Among the metabolic pathways of glycine, serine, and threonine, it has been shown that other amino acids such as glycine have a close relationship with renal pathology, not only by regulating the excretion of oxalic and citric acids in the urine and inhibiting the deposition of calcium oxalate crystals in the kidney (25), but also by protecting against inflammatory damage in the kidney (26). This provides a basis for exploring hypertensive kidney injury in ferroptosis model.…”

Section: High Expressionmentioning

confidence: 99%

Mechanism of ferroptosis in hypertensive nephropathy

Chen¹,

Wang²,

Yang³

et al. 2022

Transl Androl Urol

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Background: In recent years, it has been demonstrated that ferroptosis can be involved in a variety of kidney injury processes, but the role played by ferroptosis in hypertensive kidney injury is still unclear. The aim was to explore the mechanism of ferroptosis playing a role in hypertensive kidney disease and related signalling pathways.Methods: GSE37455 microarray data was downloaded from the Gene Expression Omnibus (GEO) database and preprocessed. Batch correction and differential analysis were performed on the normal population and the hypertensive nephropathy samples using the "sva" and "limma" packages in R software.Ferroptosis-related genes were obtained from the FerrDb database and normalized and processed using UniProt. Ferroptosis-related differentially expressed genes were obtained using Venny 2.1. and imported into the Search Tool for the Retrieval of Interacting Genes (STRING) to obtain protein-protein interactions (PPIs). The data were imported into Cytoscape 3.7.2 for processing to identify the core differential genes of ferroptosis based on nodes. Gene set enrichment analysis (GSEA) was performed on the core differential genes of ferroptosis to infer the pathway of ferroptosis action in hypertensive nephropathy. Results:The R software processing yielded 37 differential genes, including 13 upregulated genes and 24 downregulated genes. 202 ferroptosis-related genes were obtained by screening, and 3 ferroptosis-related differentially expressed genes were obtained after taking the intersection. The ferroptosis-related core differentially expressed gene albumin (ALB) was obtained by PPI network analysis and Cytoscape processing.GSEA analysis revealed that ferroptosis may act in hypertensive nephropathy through pathways such as drug metabolism-cytochrome P450, branched-chain amino acid (BCAA) metabolism, retinol metabolism, and biological processes (BPs) such as organic and amino acid metabolism and humoral immunity.Conclusions: Ferroptosis may act in the development of hypertensive nephropathy through pathways such as BCAA metabolism and retinol metabolism and BPs such as organic and amino acid metabolism and humoral immunity.

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Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 28 publications

NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes

NMR-Based Metabolomics in Differential Diagnosis of Chronic Kidney Disease (CKD) Subtypes

Integrated Proteomics and Metabolomics to Study IgA Nephropathy on Early Stage and Identification of Biomarkers

Mechanism of ferroptosis in hypertensive nephropathy

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