Anticoagulation in patients with kidney failure on dialysis: factor XI as a therapeutic target

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.