| 1. |
- Wu, Ping-Hsun, et al.
(författare)
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Exploring the Benefit of 2-Methylbutyric Acid in Patients Undergoing Hemodialysis Using a Cardiovascular Proteomics Approach
- 2019
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Short-chain fatty acids (SCFAs) can reduce pro-inflammatory parameters and oxidative stress, providing potential cardiovascular (CV) benefits. Although some evidence links SCFAs with host metabolic health via several biological mechanisms, the role of SCFA on CV disease in patients with kidney disease remains unclear. Herein, we investigate the association between a SCFA, 2-methylbutyric acid, and target CV proteomics to explore the potential pathophysiology of SCFA-related CV benefit in patients with kidney disease. Circulating 2-methylbutyric acid was quantified by high-performance liquid chromatography and 181 CV proteins by a proximity extension assay in 163 patients undergoing hemodialysis (HD). The associations between 2-methylbutyric acid and CV proteins were evaluated using linear regression analysis with age and gender, and multiple testing adjustment. The selected CV protein in the discovery phase was further confirmed in multivariable-adjusted models and evaluated by continuous scale association. The mean value of circulating 2-methylbutyric acid was 0.22 +/- 0.02 mu m which was negatively associated with bone morphogenetic protein 6 (BMP-6) according to the false discovery rate (FDR) multiple testing adjustment method. The 2-methylbutyric acid level remained negatively associated with BMP-6 (beta coefficient -1.00, 95% confidence interval -1.45 to -0.55, p < 0.001) after controlling for other CV risk factors in multivariable models. The cubic spline curve demonstrated a linear relationship. In conclusion, circulating 2-methylbutyric acid level was negatively associated with BMP-6, suggesting that this pathway maybe involved in vascular health in patients undergoing HD. However, further in vitro work is still needed to validate the translation of the mechanistic pathways.
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| 2. |
- Wu, Ping-Hsun, 1982-, et al.
(författare)
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The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C-C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.
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| 3. |
- Yi-Ting, Lin, et al.
(författare)
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Indole-3 acetic acid increased risk of impaired cognitive function in patients receiving hemodialysis
- 2019
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Ingår i: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 73, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Patients receiving hemodialysis (HD) have a higher risk of cognitive impairment and dementia than the general population. The accumulation of uremic toxins in the brain causes uremic encephalopathy, however, limited data exists to elucidate the effect of protein-bound uremic toxins on cognitive function. Here we investigate the effect of indole-3 acetic acid (IAA) and hippuric acid (HA), two different protein-bound uremic toxins from amino acid derivatives, on cognitive function by Silico and in a clinical study. Prevalent HD patients were enrolled in two independent hospitals. Serum IAA and HA were measured using mass spectrometry. Cognitive performance was measured using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Cognitive Abilities Screening Instrument (CASI) by trained psychologists. Using silico data to predict the effect of blood-brain barrier penetration was performed. The silico data demonstrated that IAA and HA had positive blood-brain barrier penetration ability. Amongst the 230 HD patients, serum IAA was associated with poor MMSE score (beta = -0.90, 95% CI -1.61 to -0.19) and poor CASI score (beta = -3.29, 95% CI -5.69 to -0.88) in stepwise multiple linear regression analysis. In logistic regression model, Serum IAA was also associated with cognitive impairment based on MMSE definition (OR, 1.96, 95% CI 1.10, 3.5) and CASI definition (OR, 2.09, 95% CI 1.21, 3.61). There was no correlation between Serum HA levels and cognitive function status. In conclusion, IAA, not HA, was associated with cognitive impairment in HD patients. Further large scale and prospective studies are needed to confirm our findings.
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| 4. |
- Yi-Ting, Lin, et al.
(författare)
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Protein-bound uremic toxins are associated with cognitive function among patients undergoing maintenance hemodialysis
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic kidney disease have a greater risk of cognitive impairment. Cerebral uremic solute accumulation causes uremic encephalopathy; however, the association of protein-bound uremic toxins on cognitive function remains unclear. The present study aimed to investigate the association of two protein-bound uremic toxins, namely indoxyl sulfate (IS) and p-cresyl sulfate (PCS), on cognitive function in patients receiving hemodialysis (HD) for at least 90 days. Circulating free form IS and PCS were quantified by liquid chromatography/mass spectrometry. Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) were used to evaluate cognitive function. In total, 260 HD patients were recruited with a mean age of 58.1 +/- 11.3 years, of which, 53.8% were men, 40% had diabetes, and 75.4% had hypertension. The analysis revealed that both free IS and free PCS were negatively associated with the CASI score and MMSE. After controlling for confounders, circulating free IS levels persisted to be negatively associated with MMSE scores [beta = -0.62, 95% confidence interval (CI): -1.16 to -0.08] and CASI scores (beta = -1.97, 95% CI: -3.78 to -0.16), mainly in the CASI domains of long-term memory, mental manipulation, language ability, and spatial construction. However, there was no correlation between free PCS and total MMSE or total CASI scores after controlling for confounders. In conclusion, circulating free form IS, but not PCS is associated with lower cognitive function test scores in HD patients. Thus, a further study is needed to evaluate whether a decrease in free IS levels can slow down cognitive decline in HD patients.
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