scholarly journals Tryptophan-Derived Uremic Toxins and Thrombosis in Chronic Kidney Disease

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 412 ◽  
Author(s):  
Tawfik Addi ◽  
Laetitia Dou ◽  
Stéphane Burtey
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Elevated Risk ◽  
Uremic Toxins ◽  
Extrinsic Pathway ◽  
Coronary Syndrome ◽  
Aryl Hydrocarbon ◽  
Hemodialysis Vascular Access ◽  
No Bioavailability

Patients with chronic kidney disease (CKD) display an elevated risk of thrombosis. Thrombosis occurs in cardiovascular events, such as venous thromboembolism, stroke, and acute coronary syndrome, and is a cause of hemodialysis vascular access dysfunction. CKD leads to the accumulation of uremic toxins, which exerts toxic effects on blood and the vessel wall. Some uremic toxins result from tryptophan metabolization in the gut through the indolic and the kynurenine pathways. An increasing number of studies are highlighting the link between such uremic toxins and thrombosis in CKD. In this review, we describe the thrombotic mechanisms induced by tryptophan-derived uremic toxins (TDUT). These mechanisms include an increase in plasma levels of procoagulant factors, induction of platelet hyperactivity, induction of endothelial dysfunction/ impairment of endothelial healing, decrease in nitric oxide (NO) bioavailability, and production of procoagulant microparticles. We focus on one important prothrombotic mechanism: The induction of tissue factor (TF), the initiator of the extrinsic pathway of the blood coagulation. This induction occurs via a new pathway, dependent on the transcription factor Aryl hydrocarbon receptor (AhR), the receptor of TDUT in cells. A better understanding of the prothrombotic mechanisms of uremic toxins could help to find novel therapeutic targets to prevent thrombosis in CKD.

scholarly journals Relation of Functional Activity of Platelets to Prognosis of Unfavorable Cardiovascular Events in Patients with Acute Coronary Syndrome. Results of a Registry Study

Kardiologiia ◽  
2019 ◽  
Vol 59 (10) ◽  
pp. 5-13
Author(s):  
N. V. Lomakin ◽  
L. I. Buryachkovskaya ◽  
A. B. Sumarokov ◽  
Z. A. Gabbasov ◽  
A. N. Gerasimov
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Kidney Disease ◽  
Functional Activity ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Coronary Syndrome ◽  
C Statistic

Aim: to assess relation ofhigh functional activity ofplatelets to prognosis ofunfavorable cardiovascular events in patients with Acute Coronary Syndrome (ACS).Materials. The study was based on the data of a single center ACS registry conducted in the Central Clinical Hospital of the Presidential Affairs Department of Russian Federation. Of 529 included patients in 425 without contraindications to double antiplatelet therapy we carried out analysis of dependence of 30 days level of unfavorable events on parameters of functional activity of platelets.Results. High on-treatment platelet reactivity (HTPR) was found to be associated with 3.5 increase of mortality in the group of patients with high cardiovascular risk. Logistic model of prognosis of unfavorable events based on multifactorial analysis of data from patients with measured platelet aggregation included chronic kidney disease, type of myocardial infarction, and degree ofplatelet aggregation >45%. C -statistic was equal to 0.77. We also present in this paper discussion of problems related to studying approaches to individualization of anti-aggregation therapy in real clinical practice and problems of organization ofsimilar studies.Conclusion. The study showed that patients with ACS increased platelet aggregation, as well as chronic kidney disease and type 2 MI are associated with a 30 day prognosis of adverse events.

scholarly journals Additive effect of in-hospital TIMI bleeding and chronic kidney disease on 1-year cardiovascular events in patients with acute coronary syndrome

2014 ◽  
Vol 30 (4) ◽  
pp. 441-450 ◽  
Author(s):  
Tsung-Hsien Lin ◽  
Wen-Ter Lai ◽  
Chi-Tai Kuo ◽  
Juey-Jen Hwang ◽  
Fu-Tien Chiang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Additive Effect ◽  
Coronary Syndrome

scholarly journals Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic Toxins

Nephron ◽  
2017 ◽  
Vol 137 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jessyca S. Brito ◽  
Natália A. Borges ◽  
Marta Esgalhado ◽  
D''Angelo C. Magliano ◽  
Christophe O. Soulage ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Uremic Toxins ◽  
Aryl Hydrocarbon

scholarly journals Free 25-Vitamin D Is Correlated with Cardiovascular Events in Prevalent Hemodialysis Patients but Not with Markers of Renal Mineral Bone Disease

2019 ◽  
Vol 44 (3) ◽  
pp. 344-353 ◽  
Author(s):  
Xin  Chen ◽  
Yong-Ping  Lu ◽  
Ting  Luo ◽  
Hong-Wei Wu ◽  
Su-Fen Cai ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Hemodialysis Patients ◽  
Biologically Active ◽  
Blood Concentrations ◽  
Coronary Syndrome ◽  
Vitamin D Levels ◽  
Free Vitamin D

Free vitamin D is the biologically active form of vitamin D. Vitamin D deficiency is associated with cardiovascular disease, the most common cause of mortality in hemodialysis patients. The goal of our current study was to investigate the relation between blood concentrations of free 25-hydroxyvitamin D with cardiovascular events in end-stage chronic kidney disease patients on hemodialysis, because this is unknown so far. We measured free vitamin D levels in 117 stable consecutive prevalent patients in September as a surrogate of vitamin D exposure during the past 6 months, and recorded the number of cardiovascular events during the previous 6 months defined as hospitalization due to heart failure, episodes of acute coronary syndrome, and stroke. Fourteen events occurred during the observation period. In patients without any cardiovascular events the free vitamin D levels were significantly higher as compared to those with cardiovascular events (patients without events: 5.68 [4.37–9.27] pg/mL; patients with events: 4.74 [3.46–5.37] pg/mL, p = 0.015). This finding remained stable after multiple regression analysis considering confounding factors such as age, time on dialysis, preexisting diabetes, hypertension, and coronary heart disease. In conclusion, our study shows that free vitamin D serum concentrations are independently associated with major cardiovascular events in chronic kidney disease patients on dialysis.

Meta-Analysis of Potent P2Y12-ADP Receptor Antagonist Therapy Compared to Clopidogrel Therapy in Acute Coronary Syndrome Patients with Chronic Kidney Disease

2018 ◽  
Vol 118 (10) ◽  
pp. 1839-1846 ◽  
Author(s):  
Laurent Bonello ◽  
Marc Laine ◽  
Gilles Lemesle ◽  
Etienne Puymirat ◽  
Thibaut Dabry ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Group Analysis ◽  
Cochrane Library ◽  
Coronary Syndrome ◽  
Clopidogrel Therapy ◽  
Adp Receptor

Background The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk–benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown. Objective We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS. Methods We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings. Results We included data from three sub-group analysis of randomized clinical trials and two prospective observational studies (n = 31,234). Overall, PPAs were associated with lower rates of major cardiovascular events, with a pooled hazard ratio (pHR) of 0.88 (95% confidence interval [CI]: 0.79–0.99; p = 0.03), without increased bleedings (pHR = 1.10) (95% CI: 0.95–1.27; p = 0.18). In a sensitivity analysis restricted to studies enrolling invasively managed patients, the benefit of PPA on MACE was maintained (pHR = 0.85) (95% CI: 0.77–0.93; p < 0.001), including a reduction in mortality (pHR = 0.82) (95% CI: 0.7–0.96; p = 0.016). Conclusion Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.

scholarly journals Association of digoxin with mortality in patients with advanced chronic kidney disease: A population-based cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245620
Author(s):  
Lii-Jia Yang ◽  
Shan-Min Hsu ◽  
Ping-Hsun Wu ◽  
Ming-Yen Lin ◽  
Teng-Hui Huang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Population Based ◽  
Hazard Ratio ◽  
User Group ◽  
Coronary Syndrome

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate—eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23–2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75–1.86), ischemic stroke (sHR 1.42; 95% CI 0.85–2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78–1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

Aryl Hydrocarbon Receptor and Uremic Toxins from the Gut Microbiota in Chronic Kidney Disease Patients: Is There a Relationship between Them?

Biochemistry ◽  
2019 ◽  
Vol 58 (15) ◽  
pp. 2054-2060 ◽  
Author(s):  
Jessyca Sousa de Brito ◽  
Natália Alvarenga Borges ◽  
Juliana Saraiva dos Anjos ◽  
Lia Sumie Nakao ◽  
Milena Barcza Stockler-Pinto ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Aryl Hydrocarbon Receptor ◽  
Uremic Toxins ◽  
Aryl Hydrocarbon
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