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Anticoagulation in patients with kidney failure on dialysis: factor XI as a therapeutic target
Kidney International ( IF 14.8 ) Pub Date : 2021-09-30 , DOI: 10.1016/j.kint.2021.08.028
John Eikelboom 1 , Jürgen Floege 2 , Ravi Thadhani 3 , Jeffrey I Weitz 4 , Wolfgang C Winkelmayer 5
Affiliation  

Chronic kidney disease is present in almost 10% of the world population and is associated with excess mortality and morbidity. Reduced glomerular filtration rate and the presence and extent of proteinuria, key domains of chronic kidney disease, have both been shown to be strong and independent risk factors for cardiovascular disease. Patients with kidney failure requiring dialysis are at highest risk for cardiovascular events (e.g., stroke or myocardial infarction), and of developing chronic cardiovascular conditions, such as heart failure. Despite the high burden of cardiovascular disease, there is a paucity of evidence supporting therapies to reduce this risk. Although long-term anticoagulant treatment has the potential to prevent thromboembolism in persons with kidney failure on dialysis, this possibility remains understudied. The limited data available on anticoagulation in patients with kidney failure has focused on vitamin K antagonists or direct oral anticoagulants that inhibit thrombin or factor (F) Xa. The risk of bleeding is a major concern with these agents. However, FXI is emerging as a potential safer target for new anticoagulants because FXI plays a greater part in thrombosis than in hemostasis. In this article, we (i) explain the rationale for considering anticoagulation therapy in patients with kidney failure to reduce atherothrombotic events, (ii) highlight the limitations of current anticoagulants in this patient population, (iii) explain the potential benefits of FXI inhibitors, and (iv) summarize ongoing studies investigating FXI inhibition in patients with kidney failure on dialysis.



中文翻译:

透析肾功能衰竭患者的抗凝:因子 XI 作为治疗靶点

慢性肾病存在于世界近 10% 的人口中,并且与过高的死亡率和发病率有关。肾小球滤过率降低以及蛋白尿的存在和程度(慢性肾病的关键领域)均已被证明是心血管疾病的重要独立危险因素。需要透析的肾功能衰竭患者发生心血管事件(例如中风或心肌梗塞)和发生慢性心血管疾病(例如心力衰竭)的风险最高。尽管心血管疾病的负担很高,但缺乏支持降低这种风险的疗法的证据。尽管长期抗凝治疗有可能预防透析肾衰竭患者的血栓栓塞,但这种可能性仍未得到充分研究。关于肾衰竭患者抗凝的有限数据集中在维生素 K 拮抗剂或抑制凝血酶或因子 (F) Xa 的直接口服抗凝剂上。出血风险是这些药物的主要关注点。然而,FXI 正在成为新抗凝剂的潜在更安全目标,因为 FXI 在血栓形成中的作用比止血作用更大。在本文中,我们 (i) 解释了考虑对肾功能衰竭患者进行抗凝治疗以减少动脉粥样硬化血栓形成事件的基本原理,(ii) 强调当前抗凝剂在该患者人群中的局限性,(iii) 解释 FXI 抑制剂的潜在益处, (iv) 总结正在进行的对透析肾衰竭患者 FXI 抑制的研究。

更新日期:2021-11-18
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