Antithrombotic Therapy in Patients With Chronic Kidney Disease
Authors: Davide Capodanno, Dominick J. Angiolillo
Journal: Circulation (2012)

C hronic kidney disease (CKD) is a pandemic public health problem, with Ͼ500 million people worldwide estimated to have some form of kidney injury. 1 Survey data suggest that the prevalence of CKD in the United States has increased between 1988 to 1994 and 1999 to 2004 from 10% to 13%, reaching a rate of 14% in 2010. 2,3Overlapping conditions such as acute kidney injury play an important role in the growing epidemiology of CKD, and underlying CKD is in turn an important risk factor for acute kidney injury and end-stage renal disease.Key factors contributing to the increased prevalence of CKD include the aging population and the growing burden of diabetes mellitus. 4The prevalence of stage 3 or 4 CKD has been reported to be Ϸ38% for adults Ն70 years old versus Ϸ1% in adults 20 to 39 years of age. 2,5atients with diabetes mellitus are found to present with CKD in about one third of cases, with diabetic nephropathy as the most common cause of renal impairment. 6][9][10] This underscores the importance of antithrombotic treatment strategies in these patients.However, the risk-tobenefit ratio with antithrombotic therapies may be altered in CKD.2][13] Importantly, bleeding has emerged as an independent predictor of adverse outcomes, including mortality. 14 -17 Moreover, patients with severe CKD are less likely to receive medications of proven benefit. 18,19verall, these findings contribute to explain why patients with reduced renal function have poorer prognosis compared with patients with preserved renal function.Defining the fine balance between safety and efficacy remains a challenge in patients with CKD treated with antithrombotic therapy.Unfortunately, dosing errors, which commonly occur in patients with CKD, accounts for almost one third of adverse drug events, and more than half of these errors occur at the prescription stage. 20Therefore, understanding whether a drug should or should not be prescribed and individualizing dosage regimens are key to balancing the safety and efficacy profiles of antithrombotic medications in CKD patients.This article provides an overview of the currently available evidence on the use of antithrombotic therapy in patients with CKD.In particular, a description of thrombosis and hemostatic profiles that characterize CKD patients, considerations for use of antithrombotic agents, including antiplatelet and anticoagulant therapies, and a review of the safety and efficacy data in CKD patients in the settings of coronary artery disease manifestations and atrial fibrillation are provided.A discussion of antithrombotic therapy in patients with acute kidney injury and end-stage renal disease is beyond the scope of this article. CKD: DefinitionsThe Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation defines CKD as either kidney damage or a decreased kidney glomerular filtration rate (GFR) of Ͻ60 mL ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 for Ն3 months. 21The different stages of CKD are listed in Table 1.While stages 3 through 5 are characterized by a gradient of GFR ranges, markers of structural or functional kidney damage other than GFR, including blood, urine, or imaging tests abnormalities, need to be present to establish a diagnosis of stage 1 and stage 2 CKD.Kidney failure is defined as either a GFR of Ͻ15 mL ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 or a need for initiation of kidney replacement therapy (dialysis or transplantation).End-stage renal disease is a US administrative definition that includes patients treated by dialysis or transplantation regardless of the GFR level.Many calculators are available to estimate the GFR.The National Kidney Foundation recommends using the Modification of Diet in Renal Disease equation. 22 Thrombosis and Hemostasis: Biological Considerations in Patients With CKDPatients with CKD may present with platelet dysfunction and abnormalities in the enzymatic coagulation cascade.This may explain why patients with CKD may experience 2 opposite hemostatic complications: bleeding diathesis and thrombotic tendencies.