Trimethylamine N-oxide (TMAO) is a biomarker that is effective in predicting major adverse cardiovascular (CV) events. Age-related vascular problems are significantly affected by aortic stiffness (AS), which is independently linked to CV morbidity and mortality. This study aimed to determine the association between serum TMAO levels and carotid–femoral pulse wave velocity (cfPWV) in patients receiving hemodialysis (HD) therapy. In total, 115 patients with HD were enrolled in this study. The AS group included patients whose cfPWV was >10 m/s. Using high-performance liquid chromatography and mass spectrometry, the levels of serum TMAO were measured. The AS group included 42 (36.5%) patients, and compared with the non-AS group, the rates of diabetes, hypertension, older age, systolic blood pressure, serum glucose, and TMAO levels were high. In the multivariate logistic regression analysis, serum TMAO and age were independently linked with AS after correcting for the factors significantly associated with AS. Following multivariate stepwise linear regression analysis, serum TMAO in these individuals was found to be strongly correlated with cfPWV values (p < 0.001). In patients on chronic HD, serum TMAO level is an independent measure of AS and strongly correlated with cfPWV.

The epithelial-to-mesenchymal transition (EMT) plays a key role in the pathogenesis of kidney fibrosis, and kidney fibrosis is associated with an adverse renal prognosis. Beta-mangostin (β-Mag) is a xanthone derivative obtained from mangosteens that is involved in the generation of antifibrotic and anti-oxidation effects. The purpose of this study was to examine the effects of β-Mag on renal tubulointerstitial fibrosis both in vivo and in vitro and the corresponding mechanisms involved. As shown through an in vivo study conducted on a unilateral ureteral obstruction mouse model, oral β-Mag administration, in a dose-dependent manner, caused a lesser degree of tubulointerstitial damage, diminished collagen I fiber deposition, and the depressed expression of fibrotic markers (collagen I, α-SMA) and EMT markers (N-cadherin, Vimentin, Snail, and Slug) in the UUO kidney tissues. The in vitro part of this research revealed that β-Mag, when co-treated with transforming growth factor-β1 (TGF-β1), decreased cell motility and downregulated the EMT (in relation to Vimentin, Snail, and N-cadherin) and phosphoryl-JNK1/2/Smad2/Smad3 expression. Furthermore, β-Mag co-treated with SB (Smad2/3 kinase inhibitor) or SP600125 (JNK kinase inhibitor) significantly inhibited the TGF-β1-associated downstream phosphorylation and activation of JNK1/2-mediated Smad2 targeting the Snail/Vimentin axis. To conclude, β-Mag protects against EMT and kidney fibrotic processes by mediating the TGF-β1/JNK/Smad2 targeting Snail-mediated Vimentin expression and may have therapeutic implications for renal tubulointerstitial fibrosis.

A novel cardiovascular stress biomarker known as galectin-3 might be useful for anticipating adverse cardiovascular outcomes. The objective of the current investigation was to assess the association between serum galectin-3 levels and aortic stiffness (AS) in 196 patients on peritoneal dialysis. An enzyme-linked immunosorbent examination and a cuff-based volumetric displacement were employed to determine the levels of serum galectin-3 and the carotid-femoral pulse wave velocity (cfPWV), respectively. The AS group had 48 patients in total (24.5%) with cfPWV greater than 10 m/s. The AS group, when compared with the group without AS, had a significantly higher prevalence of diabetes mellitus and hypertension in addition to greater fasting glucose levels, waist circumference, systolic blood pressure, and serum galectin-3 levels. Multivariate logistic and linear regression analysis demonstrated that serum glactin-3 levels, in addition to gender and age, were significantly and independently associated with cfPWV and AS. Serum galectin-3 levels were linked with AS, according to a receiver operating characteristic curve analysis, with an area under the curve of 0.648 (95% confidence interval, 0.576–0.714; p = 0.0018). In summary, there was a significant correlation between serum galectin-3 levels and cfPWV in patients undergoing peritoneal dialysis therapy for end-stage kidney disease.

Background and Objectives: Osteoprotegerin (OPG), a soluble glycoprotein found in serum, has been associated with both the presence and severity of atherosclerosis. OPG is regarded as the mediator in the process of vascular endothelial dysfunction. Impaired endothelial function has an intimate link with hypertension (HTN) and is associated with significant morbidity and mortality. This study was to investigate the connection between OPG and endothelial dysfunction in patients having HTN. Materials and Methods: There are 102 patients with HTN included. For the purpose of determining the levels of OPG, a commercial enzyme-linked immunosorbent test kit was applied. The vascular reactivity index (VRI), which is assessed via the digital thermal monitoring, provides information on endothelial function. Results: Ten patients with HTN (9.8%) were classified as having poor vascular reactivity (VRI < 1.0), 46 HTN patients (45.1%) as having intermediate vascular reactivity (1.0 ≤ VRI < 2.0), and 46 HTN patients (45.1%) were classified as having high vascular reactivity (VRI ≥ 2.0). A greater serum OPG level (p < 0.001) and older age (p = 0.022) were linked to impaired vascular reactivity. The estimated glomerular filtration rate (r = 0.196, p = 0.048) was positively correlated with VRI values in hypertensive participants, while advanced age (r = −0.222, p = 0.025) and the log-transformed OPG level (log-OPG, r = −0.357, p < 0.001) were negatively correlated with VRI. Serum log-OPG level was shown to be strongly and independently correlated with VRI values in HTN individuals after multivariable forward stepwise linear regression analysis (β = −0.357, adjusted R² change = 0.119, p < 0.001). Conclusions: In patients with HTN, serum OPG levels were adversely correlated with VRI and probably had a role in endothelial dysfunction.

BACKGROUND Lipoprotein (a) [Lp(a)] is associated with atherosclerosis and cardiovascular mortality in patients with kidney failure. Aortic stiffness (AS), measured primarily by carotid-femoral pulse wave velocity (cfPWV), reflects vascular aging and precedes end-organ failure. This study aimed to evaluate the association between serum Lp(a) levels and cfPWV in patients undergoing peritoneal dialysis (PD). MATERIAL AND METHODS In this cross-sectional study, which included 148 patients with long-term PD for end-stage kidney failure, cfPWV was measured using a cuff-based method. AS was defined as a cfPWV exceeding 10 m/s, and an enzyme-linked immunosorbent assay was used to determine serum Lp(a) levels. Univariate and multivariate regression analyses were performed to identify the clinical correlates of AS. RESULTS There were 32 (21.6%) patients diagnosed with AS. Based on the multivariate logistic regression analysis, the odds ratio for AS was 1.007 (95% confidence interval, 1.003-1.011; P=0.001) for every 1 mg/L increase in Lp(a) levels. Multivariate linear regression analysis showed that Lp(a) (P<0.001), age (P=0.003), waist circumference (P=0.008), systolic blood pressure (P=0.010), and diabetes mellitus (P<0.001) were positively associated with cfPWV. The area under the receiver operating characteristic curve for Lp(a) in differentiating AS from non-AS was 0.770 (95% confidence interval, 0.694-0.835; P<0.0001). CONCLUSIONS Serum Lp(a) level was independently associated with cfPWV and AS in patients with PD.

Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite, participates in the atherogenesis and vascular stiffening that is closely linked with cardiovascular (CV) complications and related deaths in individuals with kidney failure undergoing peritoneal dialysis (PD) therapy. In these patients, arterial stiffness (AS) is also an indicator of adverse CV outcomes. This study assessed the correlation between serum TMAO concentration quantified with high-performance liquid chromatography and mass spectrometry and central AS measured by carotid–femoral pulse wave velocity (cfPWV) in patients with chronic PD. Of the 160 participants included, 23.8% had a cfPWV of ≥10 m/s, which fulfilled the AS criteria. Multivariable logistic regression analysis revealed that TMAO, age, and waist circumference were positively associated with AS. Multivariable stepwise linear regression showed that underlying diabetes, advanced age, waist circumference, systolic blood pressure, and logarithmic-transformed TMAO were independently correlated with cfPWV. The area under the receiver operating characteristic curve for TMAO in differentiating AS from non-AS was 0.737. In conclusion, serum TMAO level was significantly independently correlated with central AS among participants undergoing PD for end-stage kidney failure.