scholarly journals TO021DIRECT FACTOR Xa INHIBITOR APIXABAN PREVENTS ENDOTHELIAL ACTIVATION AND DAMAGE ASSOCIATED WITH CHRONIC KIDNEY DISEASE

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii87-iii87 ◽  
Author(s):  
Aleix Cases ◽  
Manel Vera ◽  
Marta Palomo ◽  
Sergi Torramade ◽  
Gines Escolar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Factor Xa ◽  
Endothelial Activation ◽  
Factor Xa Inhibitor

scholarly journals Endothelial Activation Markers in Anemic Non-Dialysis Chronic Kidney Disease Patients

2008 ◽  
Vol 110 (4) ◽  
pp. c244-c250 ◽  
Author(s):  
Tejas V. Patel ◽  
Bharati V. Mittal ◽  
Sai Ram Keithi-Reddy ◽  
Jeremy S. Duffield ◽  
Ajay K. Singh
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Endothelial Activation ◽  
Activation Markers

scholarly journals Oral Factor Xa Inhibitors versus Warfarin for the Treatment of Venous Thromboembolism in Advanced Chronic Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Tania Ahuja ◽  
Kelly Sessa ◽  
Cristian Merchan ◽  
John Papadopoulos ◽  
David Green
Keyword(s):  
Chronic Kidney Disease ◽  
Venous Thromboembolism ◽  
Kidney Disease ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Data ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Advanced Chronic Kidney Disease ◽  
Ckd Stage

Introduction. Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods. A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results. There were 56 patients evaluated, of which 39 (70%) received warfarin and 17 (30%) received an OFXai (apixaban or rivaroxaban). Tolerability at 3 months was assessed in 48/56 patients (86%). A total of 34/48 (71%) patients tolerated anticoagulation at 3 months, 12 (80%) in the OFXai arm, and 22 (67%) in the warfarin arm ( p = 0.498 ). There were 10/48 (21%) patients that experienced any bleeding events within 3 months, 7 on warfarin, and 3 on apixaban. Recurrence of thromboembolism within 3 months occurred in 3 patients on warfarin, with no recurrence in the OFXai arm. Discussion. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.

DOAC use in patients with chronic kidney disease

Phlebologie ◽  
2018 ◽  
Vol 47 (03) ◽  
pp. 146-154 ◽  
Author(s):  
S. Kücükköylü ◽  
L. C. Rump
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Calcineurin Inhibitors ◽  
Patients At Risk

SummaryDirect oral anticoagulants (DOACs) are increasingly prescribed substances in patients with indication for effective anticoagulation. Patients with chronic kidney disease (CKD) have a high burden of cardiovascular risk and are more likely to develop atrial fibrillation (AF) than patients without CKD. Patients with mild to moderate CKD benefit from DOACs, especially when having intolerance to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients with rare renal disease and hypercoagulabilic state. DOACs are to a large extent eliminated by renal excretion. Since prospective randomised data in CKD patients are sparse, the decision for anticoagulative therapy is challenging especially in patients with severe renal impairment. The direct factor Xa-inhibitors are approved for use even in patients with an estimated glomerular filtration rate (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a regular basis is essential before initiation and after start of DOAC, especially for patients at risk for acute renal failure (elderly, diabetics, patients with preexisting kidney disease). None of the DOACs is approved in CKD patients with end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors. In these patients conventional therapy with VKA is the only option, which has to be monitored closely since it has potential adverse effects.Nachdruck aus und zu zitieren als: Hämostaseologie 2017; 37: 286–294 https://doi.org/10.5482/HAMO-17-01-1657857

scholarly journals Soluble thrombomodulin reduces inflammation and prevents microalbuminuria induced by chronic endothelial activation in transgenic mice

2012 ◽  
Vol 302 (6) ◽  
pp. F703-F712 ◽  
Author(s):  
Gangaraju Rajashekhar ◽  
Akanksha Gupta ◽  
Abby Marin ◽  
Jessica Friedrich ◽  
Antje Willuweit ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cell Activation ◽  
Vascular Inflammation ◽  
Kidney Injury ◽  
Endothelial Activation ◽  
Endothelial Cell Activation ◽  
Soluble Thrombomodulin ◽  
Inflammatory Chemokines

Chronic kidney disease pathogenesis involves both tubular and vascular injuries. Despite abundant investigations to identify the risk factors, the involvement of chronic endothelial dysfunction in developing nephropathies is insufficiently explored. Previously, soluble thrombomodulin (sTM), a cofactor in the activation of protein C, has been shown to protect endothelial function in models of acute kidney injury. In this study, the role for sTM in treating chronic kidney disease was explored by employing a mouse model of chronic vascular activation using endothelial-specific TNF-α-expressing (tie2-TNF) mice. Analysis of kidneys from these mice after 3 mo showed no apparent phenotype, whereas 6-mo-old mice demonstrated infiltration of CD45-positive leukocytes accompanied by upregulated gene expression of inflammatory chemokines, markers of kidney injury, and albuminuria. Intervention with murine sTM with biweekly subcutaneous injections during this window of disease development between months 3 and 6 prevented the development of kidney pathology. To better understand the mechanisms of these findings, we determined whether sTM could also prevent chronic endothelial cell activation in vitro. Indeed, treatment with sTM normalized increased chemokines, adhesion molecule expression, and reduced transmigration of monocytes in continuously activated TNF-expressing endothelial cells. Our results suggest that vascular inflammation associated with vulnerable endothelium can contribute to loss in renal function as suggested by the tie2-TNF mice, a unique model for studying the role of vascular activation and inflammation in chronic kidney disease. Furthermore, the ability to restore the endothelial balance by exogenous administration of sTM via downregulation of specific adhesion molecules and chemokines suggests a potential for therapeutic intervention in kidney disease associated with chronic inflammation.

DOAC use in patients with chronic kidney disease

2017 ◽  
Vol 37 (04) ◽  
pp. 286-294
Author(s):  
Seher Kcükköylü ◽  
Lars Rump
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Calcineurin Inhibitors ◽  
Patients At Risk

SummaryDirect oral anticoagulants (DOACs) are increasingly prescribed substances in patients with indication for effective anticoagulation. Patients with chronic kidney disease (CKD) have a high burden of cardiovascular risk and are more likely to develop atrial fibrillation (AF) than patients without CKD. Patients with mild to moderate CKD benefit from DOACs, especially when having intolerance to vitamin K-antagonists (VKA). DOACs may in some cases be considered in patients with rare renal disease and hypercoagulabilic state. DOACs are to a large extent eliminated by renal excretion. Since prospective randomised data in CKD patients are sparse, the decision for anticoagulative therapy is challenging especially in patients with severe renal impairment. The direct factor Xa-inhibitors are approved for use even in patients with an estimated glomerular filtration rate (eGFR) between 15 and 30 ml/min. Careful monitoring of renal function on a regular basis is essential before initiation and after start of DOAC, especially for patients at risk for acute renal failure (elderly, diabetics, patients with preexisting kidney disease). None of the DOACs is approved in CKD patients with end-stage-renal-disease (ESRD) with or without dialysis. DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors. In these patients conventional therapy with VKA is the only option, which has to be monitored closely since it has potential adverse effects.

Oral anticoagulation in patients with chronic kidney disease

Neurology ◽  
2019 ◽  
Vol 92 (21) ◽  
pp. e2421-e2431 ◽  
Author(s):  
Konark Malhotra ◽  
Muhammad F. Ishfaq ◽  
Nitin Goyal ◽  
Aristeidis H. Katsanos ◽  
John Parissis ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Sensitivity Analyses ◽  
Systemic Embolism ◽  
Bleeding Events

ObjectiveData regarding the efficacy and safety of warfarin and non-vitamin K antagonist oral anticoagulant (NOAC) among patients with chronic kidney disease (CKD) remain scarce.MethodsSystematic review and meta-analysis of studies involving patients with CKD treated with oral anticoagulants were conducted to evaluate the following outcomes: ischemic stroke, intracerebral hemorrhage (ICH), combined ischemic and hemorrhagic stroke (strokecombined), stroke or systemic embolism, mortality, and major bleeding events. CKD was defined based on creatinine clearance (CrCl) ranging from mild (CrCl: 60–89 mL/min), moderate (CrCl: 30–59 mL/min), to severe (CrCl: 15–29 mL/min).ResultsFifteen studies (7 comparing NOAC vs warfarin and 8 comparing warfarin vs no anticoagulant) were identified comprising 78,053 patients. Warfarin (vs no anticoagulant) was associated with reduced risk of ischemic stroke (risk ratio [RR] = 0.68; 95% confidence interval [CI] 0.55–0.84]) and mortality (RR = 0.70; 95% CI 0.62–0.78). In comparison to warfarin, NOAC use lowered the risk of ICH (RR = 0.43; 95% CI 0.33–0.56), strokecombined (RR = 0.83; 95% CI 0.72–0.96), stroke or systemic embolism (RR = 0.73; 95% CI 0.62–0.85), and major bleeding (RR = 0.77; 95% CI 0.66–0.90). In adjusted analyses, warfarin use (vs no anticoagulant) was associated with reduced mortality (HRadj = 0.68; 95% CI 0.61–0.76), whereas NOAC (vs warfarin) use reduced the risk of ICH (HRadj = 0.39; 95% CI 0.30–0.50) and stroke or systemic embolism (HRadj = 0.75; 95% CI 0.65–0.88). Our sensitivity analyses comparing different NOACs exhibited that factor Xa inhibitors (compared to warfarin) consistently reduced strokecombined (RR = 0.84; 95% CI 0.73–0.96), mortality (RR = 0.84; 95% CI 0.70–1.00), ICH (RR = 0.45; 95% CI 0.24–0.85), and major bleeding (RR = 0.76; 95% CI 0.64–0.91).ConclusionsAmong patients with CKD treated with oral anticoagulants, NOACs present with a more favorable safety and efficacy profile for various cardiovascular outcomes.

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