Elevated Platelet Galectin-3 and Rho-Associated Protein Kinase Activity Are Associated with Hemodialysis Arteriovenous Shunt Dysfunction among Subjects with Diabetes Mellitus

Chen, Po Wei; Hsu, Ling-Wei; Chang, Hsien Yuan; Huang, Ting Chun; Yu, Jia; Liao, Hsin Yu; Lee, Cheng‐Han; Liu, Ping Yen

doi:10.1155/2019/8952414

Cited by 5 publications

(5 citation statements)

References 35 publications

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“…Third, unmeasured confounding effects may still exist despite adjusting for potential confounders by multiple regression. Fourth, impaired renal clearance, cardiac inflammation, activated platelets, and other etiologies may underlie the elevated circulating levels of galectin-3 in hemodialysis patients [ 44 , 45 , 46 ]. A close relationship between activation of the renin-angiotensin-aldosterone system and galectinse has also been observed in previous studies [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Circulating Galectin-3, Systemic Inflammation, and Protein-Energy Wasting in Chronic Hemodialysis Patients

Tsai

Chen

et al. 2021

Nutrients

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Galectin-3 reportedly participates in the inflammatory process that causes insulin resistance in the target tissues. However, the role of high plasma galectin-3 levels as an indicator of protein-energy wasting (PEW) in patients undergoing maintenance hemodialysis remains unclear. This study included 240 hemodialysis patients (64.5 [55.3−74.0] years, 35.8% women) from a tertiary medical center. A baseline assessment of demographic and clinical data, biochemical parameters, and body composition was conducted. Plasma galectin-3 and other biomarkers were measured using a multiplex bead-based immunoassay. Participants were then divided into two subgroups depending on the median value of plasma galectin-3. Malnutrition was identified using the geriatric nutritional risk index (GNRI) and the criteria of the International Society of Renal Nutrition and Metabolism. Independent risk factors for elevated plasma galectin-3 and malnutrition were identified by multivariate logistic regression. The high galectin-3 group was more likely to be older, have lower lean tissue mass and GNRI scores, be diagnosed with PEW, dialyze through a tunneled catheter, and have higher circulating IL-6, TNF-α, and MCP-1 concentrations than the low galectin-3 group. After multivariate adjustment, only low mean arterial pressure, dialyzing with tunneled cuffed catheters, and elevated systemic inflammatory markers correlated with high galectin-3 levels. Plasma galectin-3 concentrations also increased significantly in hemodialysis patients with PEW. However, compared with other commonly used nutritional indicators, galectin-3 did not show superiority in predicting PEW. Although the plasma galectin-3 levels correlated with PEW severity, this correlation disappeared after adjustment for potential confounding variables (OR, 1.000; 95% CI, 0.999–1.001). In conclusion, plasma galectin-3 is a valuable biomarker for systemic inflammation but is less prominent for PEW in patients with maintenance hemodialysis. Further identification of novel biomarkers is required to detect patients at risk for malnutrition and implement appropriate interventions.

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Section: Discussionmentioning

confidence: 99%

Relationship between Circulating Galectin-3, Systemic Inflammation, and Protein-Energy Wasting in Chronic Hemodialysis Patients

Tsai

Chen

et al. 2021

Nutrients

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“…Well-designed randomized controlled trials are required to clarify the effects of statin on AVF failure. Diabetes is an important risk factor for AVF dysfunction [ 42 , 43 ]. In addition, diabetes causes a hyperglycemia-induced upregulation of proinflammatory cytokines including IL-6 [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma Interleukin-6 Level Predicts the Risk of Arteriovenous Fistula Dysfunction in Patients Undergoing Maintenance Hemodialysis

Baek

Lee

Yang

et al. 2023

JPM

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Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.

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“…However, the absolute levels were higher in serum vs. plasma and the major difference was observed for Gal-3. The additional Gal-3 in serum may be released by platelets which do express this molecule [ 19 ], and ideally, platelet-poor plasma should be used when analyzing this marker.…”

Section: Discussionmentioning

confidence: 99%

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

Simeone

Tripaldi

Michelsen

et al. 2022

Cardiovasc Diabetol

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Background Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment. Methods Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels. Results Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p < 0.001). Liraglutide treatment, but not weight loss achieved by lifestyle counseling, decreased plasma sST2 levels (− 9%, beta = − 14.9, standard deviation 6.9, p = 0.037) while Gal-3 levels did not change. A reduction in serum hs-Troponin I was observed after intervention, due to a 19% (p = 0.29) increase in the lifestyle arm, and a 25% decrease (p = 0.033) in the liraglutide arm (between-group difference p = 0.083). Lower baseline Gal-3 levels predicted a better improvement in beta cell function after liraglutide treatment. Conclusions Liraglutide-induced reduction in sST2 and possibly hs-TnI suggests that in obese patients with prediabetes or early T2DM this drug may have a positive effect on (cardiac) fibrosis, whereas plasma level of Gal-3 before liraglutide initiation may predict response to the drug in terms of beta cell function improvement. Trial registration Eudract: 2013-001356-36

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Elevated Platelet Galectin-3 and Rho-Associated Protein Kinase Activity Are Associated with Hemodialysis Arteriovenous Shunt Dysfunction among Subjects with Diabetes Mellitus

Cited by 5 publications

References 35 publications

Relationship between Circulating Galectin-3, Systemic Inflammation, and Protein-Energy Wasting in Chronic Hemodialysis Patients

Relationship between Circulating Galectin-3, Systemic Inflammation, and Protein-Energy Wasting in Chronic Hemodialysis Patients

Plasma Interleukin-6 Level Predicts the Risk of Arteriovenous Fistula Dysfunction in Patients Undergoing Maintenance Hemodialysis

Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss

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