Terminal Phase Components of the Clotting Cascade in Patients with End-Stage Renal Disease Undergoing Hemodiafiltration or Hemodialysis Treatment

Pénzes, Krisztina; Hurják, Boglárka; Katona, Éva; Becs, Gergely; Balla, József; Muszbek, László

doi:10.3390/ijms21228426

Cited by 8 publications

(5 citation statements)

References 57 publications

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“…Accordingly, all circulating FXIIIa in the plasma is bound to FXIIIb, whereas FXIIIb is present in excess and only half of it is bound to FXIIIa 53 . Since FXIII is not an acute phase protein 55 , the increased FXIIIb we observe in WT 12h after MI is unlikely caused by increased synthesis. It seems much more likely to depict a relative increase in its unbound form, which would result from lower FXIIIa levels.…”

Section: Discussionmentioning

confidence: 79%

“…It does so by promoting inflammation, increasing neutrophil recruitment, enhancing angiogenesis and Col1a1 synthesis, as well as upregulating fibroblast proliferation. FXIIIa-depleted mice die of cardiac rupture with a 5-days mortality of 100% [52][53][54][55] . Furthermore, our sera analysis showed elevated factor XIIIb 12h after MI in WT compared to KO.…”

Section: Discussionmentioning

confidence: 99%

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Deletion of the ion channelTrpm4increases cardiac inflammatory markers and fibrosis after myocardial infarction in mice

Boukenna

Rougier

Aghagolzadeh

et al. 2022

Preprint

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BACKGROUND: The first cause of mortality worldwide is ischemic heart disease. In myocardial infarction (MI), the ischemic event causes cell death, which triggers a large inflammatory response responsible for removing necrotic material and inducing tissue repair. Endothelial cells, immune cells and fibroblasts play a key role in orchestrating this healing process. TRPM4 is a Ca2+-activated ion channel permeable to monovalent cations and its silencing or knocking out was shown to critically modify cellular functions of these non-myocytic cell types. OBJECTIVE: Our aims were to 1) evaluate the role of TRPM4 on mice survival and cardiac function after MI; and 2) investigate the role of TRPM4 in the post-MI acute and chronic inflammatory response. METHODS: We performed ligation of the left anterior descending coronary artery or sham intervention on 154 Trpm4 WT or KO male mice and monitored survival for up to 5 weeks as well as cardiac function using echocardiography at 72h and five weeks. We drew blood at different acute time points (6h, 12h, 24h) and performed time-of-flight mass spectrometry to analyze the sera proteomes. Further, we sacrificed sub-groups of mice at 24h and 72h after surgery and performed single-cell RNA sequencing on the non- myocytic cells. Lastly, we assessed fibrosis and angiogenesis at five weeks using type I collagen and CD31 immunostaining respectively. RESULTS: We observed no significant differences in survival or cardiac function post- MI between both genotypes. However, our serum proteomics data showed significantly decreased tissue injury markers such as creatine kinase M and VE-Cadherin in KO compared to WT 12h after MI. On the other hand, inflammation characterized by serum amyloid P component in the serum, as well as higher number of recruited granulocytes, M1 macrophages, M1 monocytes, Mac-6 macrophages, and expression of pro- inflammatory genes such as Il1b, Lyz2 and S100a8/a9 was significantly higher in endothelial cells, macrophages and fibroblasts of KO than of WT. This correlated with increased cardiac fibrosis and angiogenesis 5 weeks after MI in KO. CONCLUSION: Our data suggest that knocking out Trpm4 drastically increases acute inflammation post-MI, is associated with increased chronic fibrosis and does not improve survival at 5 weeks post-MI. Thus, targeting TRPM4 in the context of MI should be pondered carefully and approaches that nuance the timing of the inhibition or cellular target may be required.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Deletion of the ion channelTrpm4increases cardiac inflammatory markers and fibrosis after myocardial infarction in mice

Boukenna

Rougier

Aghagolzadeh

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…The hypothesis may be that the effect of aspirin is attenuated in patients with advanced CKD, with high treatment platelet reactivity [31], leading to insufficient heart protection or stronger affinition for COX-2, resulting in thrombotic and ischemic events in the heart, in whom COX-1 is responsible for platelet aggregation and vasoconstriction and COX-2 is for vasodilation and inhibition of platelet aggregation [31,32]. Moreover, the other possible explanation is that there are some complex imbalances of the clotting system, platelet function, and fibrinolytic system in advanced renal failure [33,34], reducing the protective effect of low-dose aspirin in thrombotic events and may enchaining the harmful effect of low-dose aspirin in clinical outcomes. However, the real pathophysiology of the hazardous effect of aspirin in the patient with advanced CKD is still needed the further exploring.…”

Section: Discussionmentioning

confidence: 99%

Hazardous Effect of Low-Dose Aspirin in Patients with Predialysis Advanced Chronic Kidney Disease Assessed by Machine Learning Method Feature Selection

et al. 2021

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Background: Low-dose aspirin (100 mg) is widely used in preventing cardiovascular disease in chronic kidney disease (CKD) because its benefits outweighs the harm, however, its effect on clinical outcomes in patients with predialysis advanced CKD is still unclear. This study aimed to assess the effect of aspirin use on clinical outcomes in such group. Methods: Patients were selected from a nationwide diabetes database from January 2009 to June 2017, and divided into two groups, a case group with aspirin use (n = 3021) and a control group without aspirin use (n = 9063), by propensity score matching with a 1:3 ratio. The Cox regression model was used to estimate the hazard ratio (HR). Moreover, machine learning method feature selection was used to assess the importance of parameters in the clinical outcomes. Results: In a mean follow-up of 1.54 years, aspirin use was associated with higher risk for entering dialysis (HR, 1.15 [95%CI, 1.10–1.21]) and death before entering dialysis (1.46 [1.25–1.71]), which were also supported by feature selection. The renal effect of aspirin use was consistent across patient subgroups. Nonusers and aspirin users did not show a significant difference, except for gastrointestinal bleeding (1.05 [0.96–1.15]), intracranial hemorrhage events (1.23 [0.98–1.55]), or ischemic stroke (1.15 [0.98–1.55]). Conclusions: Patients with predialysis advanced CKD and anemia who received aspirin exhibited higher risk of entering dialysis and death before entering dialysis by 15% and 46%, respectively.

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“…As potential markers of a prothrombotic state, Pénzes et al 22 measured the concentration of the acute phase reactant fibrinogen and the concentration and percentage activity of the fibrin stabilising factor (FXIII) in kidney failure individuals treated with HD and HDF. Pre‐dialysis, both FXIII and fibrinogen were higher than those of the normal population and further increased post‐dialysis.…”

Section: Haemostatic Alterations In Kidney Failurementioning

confidence: 99%

“…20,21 Coagulation factors Kidney failure is associated with a significant elevation of numerous coagulation factors including, fibrinogen, Factor VIII (FVIII), Von Willebrand factor (VWF) and FXIII when compared to individuals with preserved kidney function. 10,11,[21][22][23] Thrombogenic markers including thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (PF1 + 2) are also significantly elevated in kidney failure. 24,25 Coagulation factor and thrombogenic marker elevation are associated with a procoagulant state.…”

Section: Endothelial and Platelet Changesmentioning

confidence: 99%

Navigating through the haemostatic paradox in kidney failure: A practical overview

et al. 2023

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Summary Chronic kidney disease (CKD) affects around 9.1% of humankind globally resulting in a significant health burden. Some of these individuals will also require renal replacement therapy with dialysis due to complete kidney failure. Patients with CKD are known to be at increased risk of both bleeding and thrombosis. Often it is very difficult to manage these yin and yang since both risks tend to co‐exist. Clinically, very few studies have looked at the effects of antiplatelet agents and anticoagulants in this highly vulnerable subgroup of medical patients and evidence is very limited. This review attempts to explain the current state‐of‐the‐art regarding the basic science of haemostasis in patients with end‐stage kidney disease. We also try to transfer this knowledge into the clinics by looking at some common haemostasis challenges that are encountered in this cohort of patients and what evidence and guidance there is for their optimal management.

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Terminal Phase Components of the Clotting Cascade in Patients with End-Stage Renal Disease Undergoing Hemodiafiltration or Hemodialysis Treatment

Cited by 8 publications

References 57 publications

Deletion of the ion channelTrpm4increases cardiac inflammatory markers and fibrosis after myocardial infarction in mice

Deletion of the ion channelTrpm4increases cardiac inflammatory markers and fibrosis after myocardial infarction in mice

Hazardous Effect of Low-Dose Aspirin in Patients with Predialysis Advanced Chronic Kidney Disease Assessed by Machine Learning Method Feature Selection

Navigating through the haemostatic paradox in kidney failure: A practical overview

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