Role of glomerular filtration rate-modifying drugs in the development of anticoagulant-related nephropathy.
Role of glomerular filtration rate-modifying drugs in the development of anticoagulant-related nephropathy.
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DOI：
10.14814/phy2.14697
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发表时间：
2021-01
影响因子：
2.5
通讯作者：
Brodsky SV
中科院分区：
文献类型：
--
作者：
Medipally AK;Xiao M;Rovin BH;Satoskar AA;Ivanov I;Qaisar S;Brodsky SV
抗凝相关性肾病（ARN）最初在人类中被描述为华法林相关性肾病，其特征是急性肾损伤和肾脏红细胞（RBC）管型。用华法林或达比加群治疗的 5/6 肾切除术 (5/7NE) 大鼠显示出与人类疾病相似的肾功能和形态变化。肾小球滤过率（GFR）在 ARN 发病机制中的作用尚不清楚。这些研究的目的是阐明 GFR 在达比加群诱导的 5/6NE 大鼠 ARN 发病机制中的作用。 5/6NE 大鼠经口给予单独 150 mg/kg/天的达比加群或联合降低 GFR（依那普利，1.5 mg/kg/天）或增加 GFR（沙丁胺醇，4.0 mg/kg/天）的药物治疗 7 天。每天记录凝血和肾功能的变化。治疗后第7天评估肾脏形态。达比加群导致活化部分凝血活酶时间增加，但不受 GFR 修饰药物的影响。与单独使用达比加群相比，接受依那普利和达比加群治疗的 5/6NE 大鼠的血压显着降低。依那普利/达比加群治疗的动物 GFR 降低了 35%，沙丁胺醇/达比加群治疗的动物 GFR 增加了 26%。当达比加群添加 GFR 调节药物时，血清肌酐、血尿或尿肾损伤分子 (KIM-1) 水平没有变化。无论 GFR 是否发生变化，所有接受达比加群治疗的动物肾脏均出现红细胞管型。在大鼠 5/6 肾切除模型中，GFR 在达比加群诱导的急性肾损伤中没有发挥显着作用。根据这些数据，没有必要对 ARN 患者的 GFR 进行修改。肾小球滤过率 (GFR) 的变化在抗凝相关肾病 (ARN) 的发生中并没有发挥显着作用，至少在 5/6 肾切除大鼠模型中是这样。因此，使用 GFR 调节药物治疗似乎对 ARN 患者没有益处。
Anticoagulant‐related nephropathy (ARN), that was described in humans first as warfarin‐related nephropathy, is characterized by acute kidney injury and red blood cell (RBC) tubular casts in the kidney. 5/6 nephrectomy (5/7NE) rats treated with warfarin or dabigatran show changes in kidney function and morphology that are similar to human disease. The role of glomerular filtration rate (GFR) in the pathogenesis of ARN is not clear. The aim of these studies was to elucidate the role of GFR in the pathogenesis of dabigatran‐induced ARN in 5/6NE rats. 5/6NE rats were treated per os with 150 mg/kg/day dabigatran alone or with drugs that lower (enalapril, 1.5 mg/kg/day) or increase (albuterol, 4.0 mg/kg/day) GFR for 7 days. Changes in coagulation and kidney function were recorded daily. Kidney morphology was evaluated on day 7 after the treatment. Dabigatran resulted in activated partial thromboplastin time increase that was not affected by GFR‐modifying drugs. Blood pressure was significantly lower in 5/6NE rats treated with enalapril and dabigatran as compared to dabigatran alone. The GFR was decreased by 35% in enalapril/dabigatran‐ and increased by 26% in albuterol/dabigatran‐treated animals. There were no changes in serum creatinine, hematuria or urinary kidney injury molecule (KIM‐1) levels when GFR‐modifying drugs were added to dabigatran. All dabigatran‐treated animals had RBC casts in the kidney regardless of the GFR modification. GFR does not play a significant role in the dabigatran‐induced acute kidney injury in 5/6 nephrectomy model in rats. Based in these data, modification of GFR in patients with ARN is not warranted. Changes in the glomerular filtration rate (GFR) do not play a significant role in the development of anticoagulant‐related nephropathy (ARN), at least in the 5/6 nephrectomy rat model. Therefore, treatment with GFR‐modifying drugs does not appear to be beneficial for patients with ARN.
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影响因子：
4.2
作者：
Ozcan, A.;Ware, K.;Brodsky, S. V.
通讯作者：
Brodsky, S. V.
影响因子：
3
作者：
Brodsky SV;Mhaskar NS;Thiruveedi S;Dhingra R;Reuben SC;Calomeni E;Ivanov I;Satoskar A;Hemminger J;Nadasdy G;Hebert L;Rovin B;Nadasdy T
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Nadasdy T
影响因子：
19.6
作者：
Brodsky, Sergey V.;Nadasdy, Tibor;Hebert, Lee A.
通讯作者：
Hebert, Lee A.
影响因子：
8.3
作者：
Brodsky, S;Gurbanov, K;Winaver, J
通讯作者：
Winaver, J
影响因子：
13.2
作者：
Brodsky, Sergey V.;Satoskar, Anjali;Nadasdy, Tibor
通讯作者：
Nadasdy, Tibor