Unvavelling the pathophysiology and factors leading to red blood cell death in chronic kidney disease
揭示慢性肾病的病理生理学和导致红细胞死亡的因素
基本信息
- 批准号:521775394
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Renal anemia is a typical complication of chronic kidney disease and significantly impairs the performance and quality of life of patients. Renal anemia is currently treated using various modalities such as iron substitution, erythropoietin and HIF stabilizer administration. My research has demonstrated that a shortened lifespan of red blood cells also plays an important role in the development of renal anemia. Remarkably, my findings showed that anemia persisted despite the massive formation of the red blood cell generating hormone erythropoietin. A better understanding of why this severe breakdown of red blood cells occurs could provide novel insights into efficient therapeutic strategies in countering renal anemia. In this purview, the overarching aim of this research proposal is to investigate the role of various endogenous environmental factors involved in chronic renal failure in orchestrating premature cell death of red blood cells, leading to renal anemia. More specifically, the research proposed herein aims to elucidate the influence of the uremic milieu, secondary hyperparathyroidism, and hypoxia involving the Rapaport-Luebering cycle and the HIF signaling pathway. In addition, the connection between accelerated red blood cell death and renal anemia in patients before and after kidney transplantation together with the impact of immunosuppressants will be studied. Importantly, the research described in the proposal will highlight the therapeutic modulation of various red blood cell death-triggering mechanisms in vivo. For this purpose, various interventions with drugs (sevelamer, ketoprofen) and special dietary regimens (low-protein diet and low-phosphate diet) recapitulating real-life clinical scenarios will be conducted on established animal models. In addition, relevant signaling pathways (Rapaport-Luebering cycle and HIF signaling pathway) altering red blood cell metabolism and function in renal failure will be examined. Taken together, the knowledge gained from this study shall explain the role of various players contributing to the pathophysiology and hematologic complications of chronic renal failure, as well as provide novel information on efficient therapeutic targeting of renal anemia.
肾性贫血是慢性肾脏病的典型并发症,严重影响患者的体能和生活质量。肾性贫血目前使用各种方式治疗,如铁替代,促红细胞生成素和HIF稳定剂给药。我的研究表明,红细胞寿命缩短在肾性贫血的发展中也起着重要作用。值得注意的是,我的研究结果表明,尽管红细胞生成激素促红细胞生成素大量形成,贫血仍然存在。更好地理解为什么会发生这种严重的红细胞破坏,可以为对抗肾性贫血的有效治疗策略提供新的见解。在此范围内,本研究提案的总体目标是调查慢性肾衰竭中涉及的各种内源性环境因素在协调红细胞过早死亡中的作用,导致肾性贫血。更具体地说,本文提出的研究旨在阐明尿毒症环境、继发性甲状旁腺功能亢进和缺氧对Rapaport-Luebering循环和HIF信号通路的影响。此外,还将研究肾移植前后患者红细胞加速死亡与肾性贫血之间的联系以及免疫抑制剂的影响。重要的是,提案中描述的研究将突出体内各种红细胞死亡触发机制的治疗调节。为此,将在已建立的动物模型上进行药物(司维拉姆、酮洛芬)和特殊饮食方案(低蛋白饮食和低磷酸盐饮食)的各种干预,以重现现实生活中的临床场景。此外,将检查改变肾衰竭中红细胞代谢和功能的相关信号传导途径(Rapaport-Luebering循环和HIF信号传导途径)。总之,从本研究中获得的知识将解释各种参与者在慢性肾衰竭的病理生理学和血液学并发症中的作用,并提供有关肾性贫血有效治疗靶点的新信息。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Dr. Rosi Bissinger, Ph.D.其他文献
Dr. Rosi Bissinger, Ph.D.的其他文献
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{{ truncateString('Dr. Rosi Bissinger, Ph.D.', 18)}}的其他基金
Inhibition of eryptosis - a new strategy in the treatment of renal anemia
抑制红细胞凋亡——治疗肾性贫血的新策略
- 批准号:
426724658 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Research Grants
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