Soluble EPO Receptor and EPO Resistance in Dialysis

透析中可溶性 EPO 受体和 EPO 抵抗

基本信息

  • 批准号:
    8204522
  • 负责人:
  • 金额:
    $ 17.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-12-06 至 2013-11-30
  • 项目状态:
    已结题

项目摘要

Erythropoietin is a growth factor that has revolutionized the management of anemia in patients with end-stage renal disease (ESRD). A significant clinical challenge that remains in some patients is the relative resistance to erythropoietin, which leads to use of successively higher erythropoietin doses and increased risk of adverse outcomes. Chronic inflammation is an important factor contributing to erythropoietin resistance, yet the molecular pathways mediating this phenotype are unclear. Erythropoietin acts through the erythropoietin receptor (EpoR) present in erythroblasts. Importantly, alternative mRNA splicing produces a soluble form of EpoR (sEpoR) that is present in human blood. While the function of sEpoR is unknown, sEpoR may modulate erythropoietin signaling, raising the possibility of a physiologic role for this soluble receptor. No studies have systematically examined sEpoR levels in ESRD. Using archived serum samples obtained from subjects with ESRD, we have generated preliminary data to show that sEpoR is detectable as a 27kDa protein in their serum, and that higher serum sEpoR levels correlate with increased erythropoietin requirements. In addition we have preliminary data suggesting that sEpoR inhibits erythropoietin mediated signal transducer and activator of transcription 5 (Stat-5) phosphorylation in cell lines expressing EpoR. We also demonstrate that serum from patients with elevated sEpoR levels blocks this phosphorylation in ex vivo studies. The intent of this proposal is to confirm that serum with high levels of sEpoR can block erythropoietin mediated intracellular signaling in vitro by rescue with exogenous erythropoietin and inhibition of the effect after immunoadsorption of sEpoR from the serum. We will also examine the regulation of sEpoR secretion in response to inflammatory mediators known to be elevated in ESRD. Finally, we will perform two clinical studies using archived samples from large dialysis cohorts (ArMORR, US; 4D, Germany) to test the hypothesis that elevated sEpoR levels at the start of dialysis independently predict subsequent erythropoietin dose. We believe this exploratory R21 mechanism will permit a collaborative team of basic scientists and clinical investigators to address one of the most common and vexing problems faced by ESRD patients. This proposal has the potential to lead to changes in the diagnosis and management of patients with erythropoietin resistance.
促红细胞生成素是一种生长因子,已经彻底改变了贫血的管理

项目成果

期刊论文数量(0)
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RAVI THADHANI其他文献

RAVI THADHANI的其他文献

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{{ truncateString('RAVI THADHANI', 18)}}的其他基金

Support of the Emory National Primate Research Center
埃默里国家灵长类动物研究中心的支持
  • 批准号:
    10844283
  • 财政年份:
    2023
  • 资助金额:
    $ 17.55万
  • 项目类别:
PDE5i with Tadalafil Changes the Extent of Renal Damage (PITCH_ER)
PDE5i 与他达拉非一起改变肾损伤的程度 (PITCH_ER)
  • 批准号:
    8606587
  • 财政年份:
    2013
  • 资助金额:
    $ 17.55万
  • 项目类别:
Bioavailable Vitamin D Redefines Vitamin D Deficiency
生物可利用维生素 D 重新定义维生素 D 缺乏症
  • 批准号:
    8331000
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Impact of vitamin D supplementation on cardiac structure and function
补充维生素 D 对心脏结构和功能的影响
  • 批准号:
    8268146
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Impact of vitamin D supplementation on cardiac structure and function
补充维生素 D 对心脏结构和功能的影响
  • 批准号:
    8626441
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Impact of vitamin D supplementation on cardiac structure and function
补充维生素 D 对心脏结构和功能的影响
  • 批准号:
    8431335
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Impact of vitamin D supplementation on cardiac structure and function
补充维生素 D 对心脏结构和功能的影响
  • 批准号:
    9292464
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Patient Oriented Studies of Vitamin D in Chronic Kidney Disease
维生素 D 在慢性肾脏病中的以患者为导向的研究
  • 批准号:
    8279507
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Bioavailable Vitamin D Redefines Vitamin D Deficiency
生物可利用维生素 D 重新定义维生素 D 缺乏症
  • 批准号:
    8511620
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:
Patient Oriented Studies of Vitamin D in Chronic Kidney Disease
维生素 D 在慢性肾脏病中的以患者为导向的研究
  • 批准号:
    9026599
  • 财政年份:
    2012
  • 资助金额:
    $ 17.55万
  • 项目类别:

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