title: Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation.
abstract: An acute increase in international normalized ratio (INR) to >3.0 in patients with chronic kidney disease (CKD) can associate with an unexplained acute increase in serum creatinine and accelerated progression of CKD. A subset of these patients have renal tubular obstruction by casts of red blood cells, presumably the dominant mechanism of the acute kidney injury described as warfarin-related nephropathy. Here, we developed an animal model of this acute kidney injury that is based on the 5/6-nephrectomy model to aid future investigation of the pathogenesis of this condition. We found that acute excessive anticoagulation with brodifacoum ("superwarfarin") increased serum creatinine levels and hematuria in 5/6-nephrectomized rats but not in controls. In addition, morphologic findings in 5/6-nephrectomized rats included glomerular hemorrhage, occlusive red blood cell casts, and acute tubular injury, similar to the biopsy findings among affected patients. Furthermore, in the rat model, we observed an increase in apoptosis of glomerular endothelial cells. In summary, the 5/6-nephrectomy model combined with excessive anticoagulation may be a useful tool to study the pathogenesis of warfarin-related nephropathy.
authors: Department of Pathology, The Ohio State University, Columbus, OH 43210, USA.
authors: Kyle
authors: K
authors: Ware
authors: Polina
authors: P
authors: Brodsky
authors: Anjali A
authors: AA
authors: Satoskar
authors: Tibor
authors: T
authors: Nadasdy
authors: Gyongyi
authors: G
authors: Nadasdy
authors: Haifeng
authors: H
authors: Wu
authors: Brad H
authors: BH
authors: Rovin
authors: Udayan
authors: U
authors: Bhatt
authors: Jon
authors: J
authors: Von Visger
authors: Lee A
authors: LA
authors: Hebert
authors: Sergey V
authors: SV
authors: Brodsky
mesh_terms: D015110:4-Hydroxycoumarins; D000818:Animals; D000925:Anticoagulants; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006417:Hematuria / Q000209:etiology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; C013418:bromfenacoum