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Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease.

ABSTRACT: Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD). Reduced nitric oxide (NO) bioavailability has been associated with increased CVD in CKD patients. Children tend to have more exposure to acrylamide, one of the most common toxins in food. We aimed to determine whether urinary levels of acrylamide metabolites N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) are associated with CV risk markers in children with CKD. Data on 112 children and adolescents ages three to 18 years old with CKD stage G1-G4 are reported. We observed that 24 h ambulatory blood pressure monitoring (ABPM) abnormalities were greater, and left ventricular (LV) mass and ambulatory arterial stiffness index (AASI) were higher in children with CKD stage G2-G4 versus G1. Patients with CKD stage G2-G4 had a lower urinary acrylamide level, but a higher AAMA-to-GAMA ratio than those with CKD stage G1. Urinary acrylamide level was negatively associated with high systolic blood pressure (SBP) and diastolic BP (DBP) load on 24 h ABPM. Lower urinary levels of acrylamide, AAMA, and GAMA were correlated with LV mass. Additionally, GAMA are superior to AAMA related to NO-related parameters, namely citrulline and symmetric dimethylarginine (SDMA). This study suggests that determinations of urinary acrylamide level and its metabolites in the early stages of pediatric CKD may identify patients at risk of CVD. Further studies should clarify mechanisms underlying acrylamide exposure to define the treatment for protection against CVD.

SUBMITTER: Hsu CN

PROVIDER: S-EPMC7461542 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease.

Hsu Chien-Ning CN Hou Chih-Yao CY Lu Pei-Chen PC Chang-Chien Guo-Ping GP Lin Sufan S Tain You-Lin YL

International journal of molecular sciences 20200814 16

Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD). Reduced nitric oxide (NO) bioavailability has been associated with increased CVD in CKD patients. Children tend to have more exposure to acrylamide, one of the most common toxins in food. We aimed to determine whether urinary levels of acrylamide metabolites N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) are associated with CV risk markers in childre ...[more]

PMID: 32824071

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Project description:Rationale & objectiveChronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.Study designObservational study.Participants702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.PredictorsPlasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).OutcomesNeurocognitive tests of intelligence, academic achievement, and executive functions.Analytical approachLinear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.ResultsAt baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73 m2. In fully adjusted analyses, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log2FGF-23 was associated with abnormal test scores for attention regulation (P < 0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (β = 2.3 [1.0, 3.6]), Variability (β=1.4 [0.4, -2.4]), and Hit Reaction Time (β = 1.3 [0.2, 2.4]). Children in the highest FGF-23 tertile group had 7% and 9% greater cognitive risk for Hit Reaction Time and Errors of Omission compared with those in the lowest tertile, respectively. In fully adjusted analyses, higher FGF-23 tertile was associated with increased cognitive risk (P < 0.05) for Errors of Omission (β = 0.4 [0.1, 0.7]) and Hit Reaction Time (β = 0.4 [0.1, 0.7]).LimitationsThe study does not assess the cumulative effects of FGF-23 excess on cognitive function over time. Within-population stratified analyses were not performed due to limited sample size.ConclusionsIn children with CKD, higher plasma FGF-23 level is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of glomerular filtration rate.

Dataset Information

Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease.

Publications

Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease.

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