BACKGROUND/AIMS: We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN). We also previously reported that acute excessive anticoagulation with brodifacoum (superwarfarin) induces AKI in 5/6 nephrectomy (5/6NE) rats. Limitations of the brodifacoum model precluded a careful assessment of dose-response relationships. METHODS: Warfarin treatment was used in 5/6NE. RESULTS: Herein we report that warfarin treatment of 5/6NE rats resulted in a dose-dependent increase in serum creatinine (SC). The increase in SC following warfarin treatment was greater at 3 and 19 weeks after the ablative surgery, than that observed 8 weeks after the ablative surgery. The SC increase was correlated with the prothrombin time increase. Morphologically, 5/6NE, but not control rats, had acute tubular injury with RBC and RBC casts in the tubules. Treatment with vitamin K prevented SC increase and morphologic changes in the kidney associated with warfarin treatment. A single episode of WRN did not affect the progression of CKD in 5/6NE. CONCLUSION: (1) The 5/6NE model of CKD is an appropriate animal model to study the pathogenesis of WRN. (2) The pharmacokinetics of warfarin is better suited to the study of WRN than that of brodifacoum. (3) The more advanced stages of 5/6NE are more susceptible to WRN than the earlier stages. (4) Vitamin K treatment prevents WRN.
BACKGROUND/AIMS: We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN). We also previously reported that acute excessive anticoagulation with brodifacoum (superwarfarin) induces AKI in 5/6 nephrectomy (5/6NE) rats. Limitations of the brodifacoum model precluded a careful assessment of dose-response relationships. METHODS:Warfarin treatment was used in 5/6NE. RESULTS: Herein we report that warfarin treatment of 5/6NErats resulted in a dose-dependent increase in serum creatinine (SC). The increase in SC following warfarin treatment was greater at 3 and 19 weeks after the ablative surgery, than that observed 8 weeks after the ablative surgery. The SC increase was correlated with the prothrombin time increase. Morphologically, 5/6NE, but not control rats, had acute tubular injury with RBC and RBC casts in the tubules. Treatment with vitamin K prevented SC increase and morphologic changes in the kidney associated with warfarin treatment. A single episode of WRN did not affect the progression of CKD in 5/6NE. CONCLUSION: (1) The 5/6NE model of CKD is an appropriate animal model to study the pathogenesis of WRN. (2) The pharmacokinetics of warfarin is better suited to the study of WRN than that of brodifacoum. (3) The more advanced stages of 5/6NE are more susceptible to WRN than the earlier stages. (4) Vitamin K treatment prevents WRN.
Authors: Kyle Ware; Polina Brodsky; Anjali A Satoskar; Tibor Nadasdy; Gyongyi Nadasdy; Haifeng Wu; Brad H Rovin; Udayan Bhatt; Jon Von Visger; Lee A Hebert; Sergey V Brodsky Journal: J Am Soc Nephrol Date: 2011-09-01 Impact factor: 10.121
Authors: Sergey V Brodsky; Tibor Nadasdy; Brad H Rovin; Anjali A Satoskar; Gyongyi M Nadasdy; Haifeng M Wu; Udayan Y Bhatt; Lee A Hebert Journal: Kidney Int Date: 2011-03-09 Impact factor: 10.612
Authors: Sergey V Brodsky; Michael Collins; Edward Park; Brad H Rovin; Anjali A Satoskar; Gyongyi Nadasdy; Haifeng Wu; Udayan Bhatt; Tibor Nadasdy; Lee A Hebert Journal: Nephron Clin Pract Date: 2010-04-22
Authors: L C Racusen; K Solez; R B Colvin; S M Bonsib; M C Castro; T Cavallo; B P Croker; A J Demetris; C B Drachenberg; A B Fogo; P Furness; L W Gaber; I W Gibson; D Glotz; J C Goldberg; J Grande; P F Halloran; H E Hansen; B Hartley; P J Hayry; C M Hill; E O Hoffman; L G Hunsicker; A S Lindblad; Y Yamaguchi Journal: Kidney Int Date: 1999-02 Impact factor: 10.612
Authors: Sergey V Brodsky; Anjali Satoskar; Jun Chen; Gyongyi Nadasdy; Jeremiah W Eagen; Mirza Hamirani; Lee Hebert; Edward Calomeni; Tibor Nadasdy Journal: Am J Kidney Dis Date: 2009-07-04 Impact factor: 8.860
Authors: Douglas L Feinstein; Belinda S Akpa; Manuela A Ayee; Anne I Boullerne; David Braun; Sergey V Brodsky; David Gidalevitz; Zane Hauck; Sergey Kalinin; Kathy Kowal; Ivan Kuzmenko; Kinga Lis; Natalia Marangoni; Michael W Martynowycz; Israel Rubinstein; Richard van Breemen; Kyle Ware; Guy Weinberg Journal: Ann N Y Acad Sci Date: 2016-05-31 Impact factor: 5.691
Authors: Claudia Yuste; Eduardo Gutierrez; Angel Manuel Sevillano; Alfonso Rubio-Navarro; Juan Manuel Amaro-Villalobos; Alberto Ortiz; Jesus Egido; Manuel Praga; Juan Antonio Moreno Journal: World J Nephrol Date: 2015-05-06