title: Anticoagulation-related nephropathy.
abstract: Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.
authors.affiliation: Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Wheeler
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: Department of Medicine, Einstein Medical Center, Philadelphia, PA, USA.|Delaware Valley Nephrology and Hypertension Associates, Philadelphia, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Rangaswami
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D019934:International Normalized Ratio; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000925:Anticoagulants
keywords: International Normalized Ratio; acute renal injury; anticoagulants; thrombin; warfarin