- Sergey V Brodsky, MD, PhD
Sergey V Brodsky, MD, PhD
- Assistant Professor
- Department of Pathology, The Ohio State University
- Brad H Rovin, MD
Brad H Rovin, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine and Pathology
- The Ohio State University College of Medicine
- Lee A Hebert, MD
Lee A Hebert, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Ohio State University
- Wexner College of Medicine and Public Health
Anticoagulant-related nephropathy (also referred to as warfarin-related nephropathy) is a type of acute kidney injury (AKI) that may be caused by excessive anticoagulation with warfarin and other anticoagulants . Anticoagulant-related nephropathy has been associated with irreversible kidney injury in some patients and with increased risk of mortality.
While initially termed "warfarin-related nephropathy," we use the term "anticoagulant-related nephropathy" because the entity has been associated with anticoagulants other than warfarin .
This topic reviews the epidemiology, pathogenesis, clinical features, and treatment of anticoagulant-related nephropathy. The differential diagnosis of AKI, glomerulonephritis, and hematuria are discussed elsewhere. (See "Diagnostic approach to the patient with subacute kidney injury in an outpatient setting" and "Differential diagnosis and evaluation of glomerular disease" and "Etiology and evaluation of hematuria in adults".)
BACKGROUND AND EPIDEMIOLOGY
Acute kidney injury (AKI) resulting from glomerular hemorrhage has been described in patients with glomerular lesions (ie, kidney disease) in the absence [3-5] and presence [6,7] of coagulopathy (International Normalized Ratio [INR] 6 to 9 range). More recently, AKI has been described among patients without underlying kidney disease and with more modest elevations of INR . A detailed biopsy study of nine patients who developed otherwise unexplained AKI in association with warfarin overdose revealed the predominant lesion of tubular injury and obstruction with red blood cells (RBCs) and RBC casts . The recognition of a characteristic histologic lesion that was associated with the clinical presentation of otherwise unexplained AKI in the setting of over-anticoagulation led to the term "anticoagulant-related nephropathy."
The incidence of anticoagulant-related nephropathy is difficult to determine. This is because studies that have examined incidence have relied upon a presumptive diagnosis of anticoagulant-related nephropathy (defined by an elevation in the serum creatinine within several days of an abnormally elevated INR) rather than a more definitive diagnosis (defined by biopsy) [8,10,11]. (See 'Diagnosis' below.)
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- Brodsky SV, Nadasdy T, Rovin BH, et al. Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 2011; 80:181.
- Brodsky SV, Satoskar A, Chen J, et al. Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis 2009; 54:1121.
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- Ware K, Brodsky P, Satoskar AA, et al. Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation. J Am Soc Nephrol 2011; 22:1856.
- Ozcan A, Ware K, Calomeni E, et al. 5/6 nephrectomy as a validated rat model mimicking human warfarin-related nephropathy. Am J Nephrol 2012; 35:356.
- Schützer KM, Svensson MK, Zetterstrand S, et al. Reversible elevations of serum creatinine levels but no effect on glomerular filtration during treatment with the direct thrombin inhibitor AZD0837. Eur J Clin Pharmacol 2010; 66:903.
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- Patel RP, Svistunenko DA, Darley-Usmar VM, et al. Redox cycling of human methaemoglobin by H2O2 yields persistent ferryl iron and protein based radicals. Free Radic Res 1996; 25:117.
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- Ware K, Qamri Z, Ozcan A, et al. N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy. Am J Physiol Renal Physiol 2013; 304:F1421.
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- Brodsky SV, Rovin BH, Hebert LA. Benefit of cyclophosphamide therapy in IgA nephritis may have been obscured by warfarin-related nephropathy in the randomized trials in which warfarin and dipyridamole were used in combination with cyclophosphamide. Nephrol Dial Transplant 2012; 27:475.
- Woo KT, Lee GS, Foo MW, Chan CM. Warfarin-related nephropathy in patients with chronic kidney disease. Kidney Int 2012; 82:113; author reply 113.