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Research Letter: Is the 129S1/SvImJ Mouse Strain More Suitable to Study Anticoagulant-Related Nephropathy Than the
Ajay Medipally1, Min Xiao1, Anjali A Satoskar1
1Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, USA.
Background:
We have previously demonstrated that excessive anticoagulation with warfarin or dabigatran may result in acute kidney injury with red blood cell (RBC) tubular casts in some patients with chronic kidney disease, and this condition was named anticoagulant-related nephropathy (ARN). 5/6 nephrectomy (5/6NE) rats treated with warfarin or dabigatran reproduce the main pathologic features of human ARN. We had reported that 5/6NE C57BL/6 mice only partially develop ARN with increased serum creatinine and hematuria but no RBC tubular casts in the kidney.
Objectives:
The aim of this study was to investigate whether ARN can develop in 5/6NE 129S1/SvImJ mice.
Methods:
5/6NE was performed in 129S1/SvImJ mice. Three weeks after 5/6NE, mice were treated with warfarin (1.0 and 1.5 mg/kg/day) or vehicle 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 to 3 folds from baseline (1.0 mg/kg/day warfarin) and 4 to 5 folds from baseline (1.5 mg/kg/day warfarin) by day 7. Serum creatinine and hematuria elevated by day 7 in a dose-dependent manner. Histologically, 2 of 8 (25%) 5/6NE mice had RBCs in the tubules, and there was acute tubular epithelial cell injury in all warfarin-treated 5/6NE 129S1/SvImJ mice.
Conclusions:
Our findings suggest that 129S1/SvImJ mouse strain is a more suitable murine model to study ARN than C57BL/6 mouse strain.
Insights
This study shows that 129S1/SvImJ mice with chronic kidney disease develop anticoagulant-related nephropathy (ARN) after warfarin treatment, making them a better model for studying ARN than C57BL/6 mice.
Area of Science:
- Nephrology
- Pharmacology
- Animal Models
Background:
- Excessive anticoagulation (warfarin, dabigatran) can cause acute kidney injury with red blood cell (RBC) tubular casts in chronic kidney disease patients, termed anticoagulant-related nephropathy (ARN).
- Previous studies showed 5/6 nephrectomy (5/6NE) rats partially model human ARN.
- However, 5/6NE C57BL/6 mice only partially developed ARN without RBC tubular casts.
Purpose of the Study:
- To investigate if 129S1/SvImJ mice with 5/6NE develop ARN.
- To establish a more suitable murine model for studying ARN.
Main Methods:
- 129S1/SvImJ mice underwent 5/6 nephrectomy (5/6NE).
- Mice received warfarin (1.0 or 1.5 mg/kg/day) or vehicle for 7 days.
- Serum creatinine, hematuria, prothrombin time (PT), and renal morphology were assessed.
Main Results:
- Warfarin increased PT dose-dependently.
- Serum creatinine and hematuria elevated significantly in a dose-dependent manner.
- Histology revealed RBCs in tubules (25%) and acute tubular injury in warfarin-treated 5/6NE 129S1/SvImJ mice.
Conclusions:
- 129S1/SvImJ mice with 5/6NE are susceptible to developing ARN.
- This strain provides a more suitable murine model for ARN research compared to C57BL/6 mice.
