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Abstract: TH-PO542

Utilization of 129S1/Sv Mice as a Model for Anticoagulant Related Nephropathy

Session Information

  • Pathology and Lab Medicine
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Brodsky, Sergey V., The Ohio State University, Columbus, Ohio, United States
  • Medipally, Ajay kumar, The Ohio State University, Columbus, Ohio, United States
  • Xiao, Min, The Ohio State University, Columbus, Ohio, United States
  • Mikhalina, Galina, Unity Hospital, Rochester, New York, United States
  • Satoskar, Anjali A., The Ohio State University, Columbus, Ohio, United States
  • Biederman, Laura, The Ohio State University, Columbus, Ohio, United States
Background

We previously demonstrated that excessive anticoagulation with warfarin or dabigatran may result in acute kidney injury in some patients with chronic kidney disease and named it anticoagulant related nephropathy (ARN). An animal model of 5/6 nephrectomy rats treated with warfarin or dabigatran reproduces the main pathologic features of ARN. We had reported that C57BL/6 mice only partially develop ARNshowing increased serum creatinine and hematuria but no red blood cell (RBC) casts in the kidney. The aim of this study was to investigate whether ARN can develop in 129S1/SvImJ mice.

Methods

5/6 nephrectomy was performed in 129S1/SvImJ mice. Three weeks after the surgery, mice were treated with warfarin (1.0 mg/kg/day and 1.5 mg/kg/day) for 7 days. Serum creatinine, hematuria, and prothrombin time (PT) were monitored daily. Renal morphology was evaluated at the end of the studies.

Results

Treatment with warfarin resulted in PT elevation 2-3 folds from baseline (1.0 mg/kg/day warfarin) and 4-5 folds from baseline (1.5 mg/kg/day warfarin) by day 7. Serum creatine elevation by day 7 was dose-depended. Similarly, hematuria was increased in a dose-depended manner. Histologically, some animals had RBCs in the tubules with acute tubular epithelial cell injury.

Conclusion

Our findings suggest that 129S1/SvImJ mouse strain could be more suitable animal model to study ARN than C57BL/6 mouse strain.

Figure 1. Effects of warfarin treatment on kidney function in 129S1/SvImJ mice.
A – Coagulation effects of warfarin treatment in 129S1/SvImJ mice. sINR was calculated as PT increase from control (as described in Methods).
B – Changes in serum creatinine in 129S1/SvImJ mice treated with warfarin.
C – Effects of warfarin treatment on hematuria in 129S1/SvImJ mice.
D – Representative image of red blood cell casts in the tubules in a 129S1/SvImJ mouse treated with 1.0 mg/kg/day warfarin for 7 days.

Funding

  • NIDDK Support