Animals were allowed to recover from the surgery for 3 weeks before the start of dabigatran treatment. The 5/6 nephrectomy was performed under a ketamine/xylazine (60 mg/7.7 mg/kg) anesthesia by a nephrectomy of the right kidney and resection of two-thirds of the left kidney as was described earlier. Ablative nephropathy (5/6 nephrectomy) surgery Male Sprague–Dawley rats (140–160 g) were allowed food and water ad libitum. MATERIALS AND METHODSĪll experiments were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals. We suggest that the clinical implications of these findings are substantial. The present work makes the case that there is a new category of AKI, anticoagulant-related nephropathy (ARN), of which vitamin K and direct thrombin inhibitors are members. This WRN is part of a broader condition involving any one of the several classes of systemic anticoagulants. Kidney biopsy done after resolution of the coagulopathy showed extensive tubular obstruction by RBC casts. However, a recent case report described AKI in a patient with dabigatran-induced coagulopathy. Little is known about the effects of these oral anticoagulants on kidney function.
These oral anticoagulants include the direct thrombin inhibitor (dabigatran etexilate), and the factor Xa inhibitor (rivaroxaban).
Recently, several novel oral anticoagulants were approved for use in the USA. The present work tests the hypothesis that the AKI associated with warfarin coagulopathy is not specific for warfarin but may be seen with other classes of systemic anticoagulants. We later developed an animal model to study WRN using the 5/6 nephrectomy model of CKD in rats. Our data indicates that WRN is remarkably common in high-risk patients who develop an acutely increased INR > 3.0. WRN can have dire consequences, particularly in chronic kidney disease (CKD) patients. We termed this condition warfarin-related nephropathy (WRN). Remarkably, there were only minor glomerular changes.
Kidney biopsy in a subset of these patients showed that there was extensive tubular obstruction by red blood cell (RBC) casts, indicating that these patients had developed severe glomerular hematuria. We found that in a significant number of patients treated with warfarin, an increased international normalized ratio (INR) > 3.0 was associated with acute kidney injury (AKI). We were the first to describe a novel renal complication of warfarin therapy. Acute kidney injury, dabigatran, warfarin-related nephropathy INTRODUCTION
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