Anticoagulant Related Nephropathy Only Partially Develops in C57BL/6 Mice: Hematuria Is Not Accompanied by Red Blood Cell Casts in the Kidney.

Anticoagulant Related Nephropathy Only Partially Develops in C57BL/6 Mice: Hematuria Is Not Accompanied by Red Blood Cell Casts in the Kidney.
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DOI:
10.3389/fmed.2020.617786
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发表时间:
2020
影响因子:
3.9
通讯作者:
Brodsky SV
Brodsky SV
中科院分区:
医学3区
文献类型:
--
作者:
Medipally AK;Xiao M;Qaisar S;Satoskar AA;Ivanov I;Rovin B;Brodsky SV

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接受抗凝治疗的患者可能会发生抗凝剂相关肾病(ARN)。用不同抗凝剂治疗的5/6肾切除大鼠表现为急性肾损伤(AKI)和类似于人类ARN的肾小管内红细胞(RBC)铸型。本研究的目的是探讨建立小鼠ARN模型的可行性。C57BL/6 5/6肾切除小鼠在术后3周给予华法林和达比加兰治疗,连续7天。每种抗凝剂各用两剂。所有抗凝药物均可引起血肌酐升高和血尿增加。华法林5.0 mg/kg/d的死亡率为63%,2.5 mg/kg/d和400 mg/kg/d的死亡率仅为13%,200 mg/kg/d的死亡率为0。尽管血尿增加,但在接受任何抗凝剂治疗的小鼠中,没有看到红细胞管型。C57BL/6小鼠5/6肾切除模型仅部分复制ARN,表现为血肌酐升高和血尿增加,但残肾未见RBC管型。
Anticoagulant-related nephropathy (ARN) may develop in patients that are on anticoagulation therapy. Rats with 5/6 nephrectomy treated with different anticoagulants showed acute kidney injury (AKI) and red blood cell (RBC) casts in the tubules similar to ARN in humans. The aim of the current study was to investigate the feasibility of inducing ARN in mice. C57BL/6 5/6 nephrectomy mice were treated with warfarin and dabigatran 3 weeks after ablative surgery for 7 days. Two doses of each anticoagulant were used. All anticoagulants resulted in serum creatinine and hematuria increase. Mortality was 63% in 5.0 mg/kg/day of warfarin but only 13% in 2.5 mg/kg/day of warfarin or in 400 mg/kg/day of dabigatran and 0% in 200 mg/kg/day of dabigatran. In spite of increasing hematuria, RBC tubular casts were not seen in mice treated with any anticoagulant. The 5/6 nephrectomy murine model in C57BL/6 mice only partially reproduced ARN in terms of increasing serum creatinine and hematuria, but there were no RBC tubular casts in the remnant kidney.