Effect of Renal Nerves on Chronic Kidney Disease

肾神经对慢性肾脏病的影响

基本信息

批准号：
10629360
负责人：
Roderick Jason Tan
金额：
$ 53.09万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10629360
关键词：
Affect American Aristolochic Acids Blood Pressure Blood flow Chemoreceptors Chronic Care Chronic Kidney Failure Clinical Research Clinical Trials Denervation Diabetes Mellitus Dialysis procedure Disease Progression Disease model Efferent Neurons Exclusion Excretory function Fiber Glomerular Filtration Rate Glucose Goals Hypertension Immunosuppression Inflammation Inflammation Mediators Inflammatory Injury Kidney Kidney Diseases Kidney Failure Knock-out Laboratories Measures Mediating Mediator Modeling Morbidity - disease rate Mus Nephrectomy Nerve Pathogenesis Patients Pelvis Perfusion Population Proteinuria Public Health Rag1 Mouse Receptor Activation Renal Blood Flow Renal Plasma Flow Renal function Renin-Angiotensin System Reperfusion Injury Research Rodent Role Sensory Sodium Sodium Chloride Stimulus Testing Therapeutic Effect Tissues Transplantation Water afferent nerve blood pressure reduction chemokine cytokine experimental study hemodynamics hypertensive improved improved outcome inhibitor insight mortality neuroregulation novel novel therapeutics pressure prevent programs pyrrolidine dithiocarbamate receptor response symporter

项目摘要

Abstract Chronic kidney disease (CKD) remains a major public health problem causing severe morbidity and mortality in affected patients. The majority of CKD patients are treated with inhibitors of the renin-angiotensin system (RAS) or sodium glucose cotransporter 2 (SGLT2) but the protection afforded by these agents is incomplete. Novel treatments are needed to advance substantially the care of CKD patients. In this regard, it is known that renal nerve activity is increased in CKD and can lead to downstream effects including hypertension, reduced function, proteinuria, and kidney disease progression. Renal denervation has been shown to protect against these effects but most clinical trials only include hypertensive-CKD patients or exclude advanced CKD patients entirely. Therefore, it is not known exactly which types of CKD can be effectively treated with renal denervation. Furthermore, the relative contributions of renal sensory afferent and sympathetic efferent nerves are not known. We hypothesize that CKD-related increases in renal inflammation activates renal sensory nerves, leading in turn to increased efferent nerve activity to worsen renal function, CKD progression and hypertension. Our proposal will analyze the activity of renal nerves during various forms of CKD in mice and whether denervation impacts disease progression. We will also search for the mediators of renal nerve activation during CKD. These novel insights would provide the rationale to broaden denervation studies to CKD patients and to understand more fully the role of renal nerves in the pathogenesis of CKD.

抽象的慢性肾脏疾病（CKD）仍然是一个主要的公共卫生问题，导致严重发病和受影响患者的死亡率。大多数CKD患者接受了用抑制剂治疗肾素 - 血管紧张素系统（RAS）或钠葡萄糖共转运蛋白2（SGLT2），但保护这些代理商提供的不完整。需要新的治疗以实质性进步 CKD患者的护理。在这方面，众所周知，CKD中的肾神经活性增加了并可能导致下游影响，包括高血压，功能降低，蛋白尿和肾脏疾病进展。肾脏去神经已被证明可以防止这些影响但是大多数临床试验仅包括高血压CKD患者或排除晚期CKD 患者完全。因此，尚不清楚哪种类型的CKD可以有效用肾脏神经治疗。此外，肾脏感觉传入的相对贡献和交感神经的神经尚不清楚。我们假设与CKD相关的增加在肾炎中神经活性恶化肾功能，CKD进展和高血压。我们的建议将分析小鼠各种形式的CKD期间肾神经的活性，以及是否是否神经影响会影响疾病的进展。我们还将寻找肾神经的介体 CKD期间的激活。这些新颖的见解将提供扩大神经保护的基本原理对CKD患者的研究，并更充分地了解肾神经在 CKD的发病机理。