- 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 adult patients 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.)
- Wheeler DS, Giugliano RP, Rangaswami J. Anticoagulation-related nephropathy. J Thromb Haemost 2016; 14:461.
- Ryan M, Ware K, Qamri Z, et al. Warfarin-related nephropathy is the tip of the iceberg: direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats. Nephrol Dial Transplant 2014; 29:2228.
- Kincaid-Smith P, Bennett WM, Dowling JP, Ryan GB. Acute renal failure and tubular necrosis associated with hematuria due to glomerulonephritis. Clin Nephrol 1983; 19:206.
- Clarkson AR, Seymour AE, Thompson AJ, et al. IgA nephropathy: a syndrome of uniform morphology, diverse clinical features and uncertain prognosis. Clin Nephrol 1977; 8:459.
- Praga M, Gutierrez-Millet V, Navas JJ, et al. Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 1985; 28:69.
- Kabir A, Nadasdy T, Nadasdy G, Hebert LA. An unusual cause of gross hematuria and transient ARF in an SLE patient with warfarin coagulopathy. Am J Kidney Dis 2004; 43:757.
- Abt AB, Carroll LE, Mohler JH. Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis. Am J Kidney Dis 2000; 35:533.
- 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.
- Brodsky SV, Collins M, Park E, et al. Warfarin therapy that results in an International Normalization Ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease. Nephron Clin Pract 2010; 115:c142.
- An JN, Ahn SY, Yoon CH, et al. The occurrence of warfarin-related nephropathy and effects on renal and patient outcomes in korean patients. PLoS One 2013; 8:e57661.
- Berger R, Salhanick SD, Chase M, Ganetsky M. Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Ann Emerg Med 2013; 61:475.
- Kadiyala D, Brewster UC, Moeckel GW. Dabigatran Induced Acute Kidney Injury The American Society of Nephrology Annual Meeting, November 1-4, 2012. San Diego, CA 2012. p. FR-PO1122.
- 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.
- Martín Cleary C, Moreno JA, Fernández B, et al. Glomerular haematuria, renal interstitial haemorrhage and acute kidney injury. Nephrol Dial Transplant 2010; 25:4103.
- Ballarín J, Arce Y, Torra Balcells R, et al. Acute renal failure associated to paroxysmal nocturnal haemoglobinuria leads to intratubular haemosiderin accumulation and CD163 expression. Nephrol Dial Transplant 2011; 26:3408.
- 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.
- Tracz MJ, Alam J, Nath KA. Physiology and pathophysiology of heme: implications for kidney disease. J Am Soc Nephrol 2007; 18:414.
- Homsi E, Janino P, de Faria JB. Role of caspases on cell death, inflammation, and cell cycle in glycerol-induced acute renal failure. Kidney Int 2006; 69:1385.
- 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.
- Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11:R31.
- 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.