Identification of Metabolite Markers Associated with Kidney Function

Peng, Hongquan; Liu, Xun; Aoieong, Chiwa; Tou, Tou; Tsai, Tsungyang; Ngai, Kamleong; Cheang, Hao I; Li, Zhi; Liu, Peijia; Zhu, Haibin

doi:10.1155/2022/6190333

Cited by 14 publications

(9 citation statements)

References 28 publications

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“…In this study, we found that in pyrimidine metabolism and histidine metabolism (Figures 4B,C), orotidine-5P, pseudouridine, 3-Ureidopropionate, urea, 1-Methyl-L-histidine, Hydantoin-5-propionate, N-Formimino-Lglutamate and imidazole lactate rise as mGFR decreases. Consistent with previously reported results, pseudouridine is extremely correlated with mGFR and might be an ideal biomarker for CKD (Peng et al, 2022). Urea is an endogenous marker in CKD (Weiner et al, 2015).…”

Section: Discussionsupporting

confidence: 91%

Metabolic profiling identifies the significance of caffeine metabolism in CKD

Guo

Peng²,

Peijia³

et al. 2023

Front. Bioeng. Biotechnol.

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Background: With the development of chronic kidney disease (CKD), there are various changes in metabolites. However, the effect of these metabolites on the etiology, progression and prognosis of CKD remains unclear.Objective: We aimed to identify significant metabolic pathways in CKD progression by screening metabolites through metabolic profiling, thus identifying potential targets for CKD treatment.Methods: Clinical data were collected from 145 CKD participants. GFR (mGFR) was measured by the iohexol method and participants were divided into four groups according to their mGFR. Untargeted metabolomics analysis was performed via UPLC-MS/MSUPLC–MSMS/MS assays. Metabolomic data were analyzed by MetaboAnalyst 5.0, one-way ANOVA, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) to identify differential metabolites for further analysis. The open database sources of MBRole2.0, including KEGG and HMDB, were used to identify significant metabolic pathways in CKD progression.Results: Four metabolic pathways were classified as important in CKD progression, among which the most significant was caffeine metabolism. A total of 12 differential metabolites were enriched in caffeine metabolism, four of which decreased with the deterioration of the CKD stage, and two of which increased with the deterioration of the CKD stage. Of the four decreased metabolites, the most important was caffeine.Conclusion: Caffeine metabolism appears to be the most important pathway in the progression of CKD as identified by metabolic profiling. Caffeine is the most important metabolite that decreases with the deterioration of the CKD stage.

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Section: Discussionsupporting

confidence: 91%

Metabolic profiling identifies the significance of caffeine metabolism in CKD

Guo

Peng²,

Peijia³

et al. 2023

Front. Bioeng. Biotechnol.

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“…28 N6-carbamoylthreonyladenosine was associated with increased all HF risk in the fully adjusted model. It was previously associated with eGFR, 29 which could explain the slight increase in HR in our model 2. But such increase was not observed in HFpEF subtype analysis, suggesting N6-carbamoylthreonyladenosine might have a different effect on patients with HFpEF than other HF types.…”

Section: Metabolic Signatures Of Hf Hfpef and Hfrefsupporting

confidence: 50%

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults

Liu,

Nguyen,

Wong

et al. 2024

Circ: Heart Failure

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BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults. METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication. RESULTS: Sixty metabolites (hazard ratios range, 0.79–1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19–1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017–0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors ( P <0.05). CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

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“…Consistent with our finding, it has been reported that N6-carbamoylthreonyladenosine was significantly associated with systolic blood pressure ( 41 ). It has been identified as a biomarker for chronic kidney disease progression in children ( 50 , 51 ) and highly correlated with glomerular filtration rate ( 52 ). Hypertension can often lead to end organ damage including renal dysfunction and chronic kidney disease ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling reveals key metabolites associated with hypertension progression

Al Ashmar,

Anwardeen,

Anlar

et al. 2024

Front. Cardiovasc. Med.

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IntroductionPre-hypertension is a prevalent condition among the adult population worldwide. It is characterized by asymptomatic elevations in blood pressure beyond normal levels but not yet reaching the threshold for hypertension. If left uncontrolled, pre-hypertension can progress to hypertension, thereby increasing the risk of serious complications such as heart disease, stroke, kidney damage, and others.ObjectiveThe precise mechanisms driving the progression of hypertension remain unknown. Thus, identifying the metabolic changes associated with this condition can provide valuable insights into potential markers or pathways implicated in the development of hypertension.MethodsIn this study, we utilized untargeted metabolomics profiling, which examines over 1,000 metabolites to identify novel metabolites contributing to the progression from pre-hypertension to hypertension. Data were collected from 323 participants through Qatar Biobank.ResultsBy comparing metabolic profiles between pre-hypertensive, hypertensive and normotensive individuals, six metabolites including stearidonate, hexadecadienoate, N6-carbamoylthreonyladenosine, 9 and 13-S-hydroxyoctadecadienoic acid (HODE), 2,3-dihydroxy-5-methylthio- 4-pentenoate (DMTPA), and linolenate were found to be associated with increased risk of hypertension, in both discovery and validation cohorts. Moreover, these metabolites showed a significant diagnostic performance with area under curve >0.7.ConclusionThese findings suggest possible biomarkers that can predict the risk of progression from pre-hypertension to hypertension. This will aid in early detection, diagnosis, and management of this disease as well as its associated complications.

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Identification of Metabolite Markers Associated with Kidney Function

Cited by 14 publications

References 28 publications

Metabolic profiling identifies the significance of caffeine metabolism in CKD

Metabolic profiling identifies the significance of caffeine metabolism in CKD

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults

Metabolomic profiling reveals key metabolites associated with hypertension progression

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