Warfarin Dosing and Outcomes in Chronic Kidney Disease: A Closer Look at Warfarin Disposition

Abstract

Background: Chronic Kidney Disease (CKD) is a prevalent worldwide health problem. Patients with CKD are more prone to developing cardiovascular complications such as atrial fibrillation and stroke. This warrants the use of oral anticoagulants, such as warfarin, in this population. While the efficacy and safety of warfarin in this setting remain controversial, a growing body of evidence emphasizes that warfarin use in CKD can be problematic. This review discusses 1) warfarin use, dosing and outcomes in CKD patients; and 2) possible pharmacokinetic mechanisms for altered warfarin dosing and response in CKD.

Methods: Structured search and review of literature articles evaluating warfarin dosing and outcomes in CKD. Data and information about warfarin metabolism, transport, and pharmacokinetics in CKD were also analyzed and summarized.

Results: The literature data suggest that changes in warfarin pharmacokinetics such as protein binding, nonrenal clearance, the disposition of warfarin metabolites may partially contribute to altered warfarin dosing and response in CKD.

Conclusion: Although the evidence to support warfarin use in advanced CKD is still unclear, this synthesis of previous findings may help in improving optimized warfarin therapy in CKD settings.

Keywords: Warfarin; chronic kidney disease; dose; metabolism; outcomes; pharmacokinetics..