Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging

Yamaguchi, Yûko; Zampino, Marta; Moaddel, Ruin; Chen, Teresa K.; Tian, Qu; Ferrucci, Luigi; Semba, Richard D.

doi:10.1007/s11306-020-01762-3

Cited by 34 publications

(24 citation statements)

References 64 publications

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“…Blood was collected from participants at the National Institute on Aging Clinical Research Unit, Medstar Harbor Hospital in Baltimore, MD, following a standardized protocol, as described previously [ 40 ]. Participants were not allowed to smoke, exercise, or take medications before the blood samples were collected.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal associations between blood lysophosphatidylcholines and skeletal muscle mitochondrial function

et al. 2022

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Lysophosphatidylcholines (LPCs) are phospholipids critical in the synthesis of cardiolipin, an essential component of mitochondrial membranes. Lower plasma LPCs have been cross-sectionally associated with lower skeletal muscle mitochondrial function, but whether lower LPCs and their decline over time are longitudinally associated with an accelerated decline of mitochondria function is unknown. We analyzed data from 184 participants in the Baltimore Longitudinal Study of Aging (mean age: 74.5 years, 57% women, 25% black) who had repeated measures of plasma LPCs (16:0, 16:1, 17:0, 18:0, 18:1, 18:2, 20:3, 20:4, 24:0, and 28:1) by liquid chromatography-tandem mass spectrometry and repeated measures of skeletal muscle oxidative capacity (kPCr) assessed by 31P magnetic resonance spectroscopy over an average of 2.4 years. Rates of change in kPCr and each LPC were first estimated using simple linear regression. In multivariable linear regression models adjusted for baseline demographics and PCr % depletion, lower baseline LPC 16:1 and faster rates of decline in LPC 16:1 and 18:1 were significantly associated with a faster rate of decline in kPCr (B = − 0.169, 95% CI: − 0.328, − 0.010, p = 0.038; B = 0.209, 95% CI: 0.065, 0.352, p = 0.005; B = 0.156, 95% CI: 0.011, 0.301, p = 0.035, respectively). Rates of change in other LPCs were not significantly associated with change in kPCr (all p > 0.05). Lower baseline concentrations and faster decline in selected plasma lysophosphatidylcholines over time are associated with faster decline in skeletal muscle mitochondrial function. Strategies to prevent the decline of plasma LPCs at an early stage may slow down mitochondrial function decline and impairment during aging.

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Section: Methodsmentioning

confidence: 99%

Longitudinal associations between blood lysophosphatidylcholines and skeletal muscle mitochondrial function

et al. 2022

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“…Plasma levels of acetylcarnitine, butyrylcarnitine and carnitine have been associated with higher odds of chronic kidney disease [ 24 ]. In our work, the intracellular content in acetylcarnitine ( Figure S6A )—an ester involved in energy storage—decreased during short-term hypoxia (i.e., 0.5 or 5 h hypoxia).…”

Section: Resultsmentioning

confidence: 99%

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography–Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells

Bernardo-Bermejo

Sánchez-López

Tan

et al. 2021

IJMS

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Oxygen deficiency in cells, tissues, and organs can not only prevent the proper development of biological functions but it can also lead to several diseases and disorders. In this sense, the kidney deserves special attention since hypoxia can be considered an important factor in the pathophysiology of both acute kidney injury and chronic kidney disease. To provide better knowledge to unveil the molecular mechanisms involved, new studies are necessary. In this sense, this work aims to study, for the first time, an in vitro model of hypoxia-induced metabolic alterations in human proximal tubular HK-2 cells because renal proximal tubules are particularly susceptible to hypoxia. Different groups of cells, cultivated under control and hypoxia conditions at 0.5, 5, 24, and 48 h, were investigated using untargeted metabolomic approaches based on reversed-phase liquid chromatography–mass spectrometry. Both intracellular and extracellular fluids were studied to obtain a large metabolite coverage. On the other hand, multivariate and univariate analyses were carried out to find the differences among the cell groups and to select the most relevant variables. The molecular features identified as affected metabolites were mainly amino acids and Amadori compounds. Insights about their biological relevance are also provided.

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“…A cross-sectional study recruiting 928 men (mean age: 18.5 ± 1.2) showed that DHEAS was inversely related to creatinine clearance in lean participants ( 16 ). The targeted metabolomics evaluating 450 plasma metabolites also proved that DHEAS was also inversely associated with eGFR in 616 adults ( 42 ). However, in patients with T2DM, low DHEAS concentrations were proved to be a risk predictor of urinary albumin excretion among men and women ( 43 , 44 ).…”

Section: Discussionmentioning

confidence: 98%

Low Serum Dehydroepiandrosterone Is Associated With Diabetic Kidney Disease in Men With Type 2 Diabetes Mellitus

Zhang

Xiao

et al. 2022

Front. Endocrinol.

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BackgroundThe associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with diabetic kidney disease (DKD) remained unclear. Thus, this cross-sectional study aimed to explore the associations of DHEA and DHEAS with the risk of DKD in patients with T2DM.MethodsThe information of 1251 patients with T2DM were included in this study. Serum DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry assays. Multivariate logistic regression analyses were used to assess the associations of DHEA and DHEAS with DKD as well as high urine albumin to creatinine ratio (ACR).ResultsIn men with T2DM, the risk of DKD decreased with an increasing DHEA concentration after adjustment for traditional risk factors; the fully adjusted OR (95% CI) for tertile3 vs tertile1 was 0.37 (0.19-0.70; P = 0.010 for trend). Similarly, when taking high ACR as the outcome, low DHEA levels were still significantly associated with increased odds of high ACR (OR, 0.37; 95% CI, 0.19–0.72 for tertile3 vs tertile1; P = 0.012 for trend). The restricted cubic spline showed that the risk of DKD gradually decreased with the increment of serum DHEA levels (P-overall = 0.007; P-nonlinear = 0.161). DHEAS was not independently associated with the risk of DKD in men. In contrast, no significant relationships were found between DHEA and DHEAS and the risk of DKD in women (all P > 0.05).ConclusionsIn men with T2DM, low serum DHEA levels were independently related to the risk of DKD after adjustment for traditional risk factors. Our finding highlights the potential role of DHEA in the development of DKD in men with T2DM.

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Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging

Cited by 34 publications

References 64 publications

Longitudinal associations between blood lysophosphatidylcholines and skeletal muscle mitochondrial function

Longitudinal associations between blood lysophosphatidylcholines and skeletal muscle mitochondrial function

Exploratory Metabolomic Analysis Based on Reversed-Phase Liquid Chromatography–Mass Spectrometry to Study an In Vitro Model of Hypoxia-Induced Metabolic Alterations in HK-2 Cells

Low Serum Dehydroepiandrosterone Is Associated With Diabetic Kidney Disease in Men With Type 2 Diabetes Mellitus

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