Effect of Renal Nerves on Chronic Kidney Disease

肾神经对慢性肾脏病的影响

• 批准号: 10410615
• 负责人: Roderick Jason Tan
• 金额: $ 54.25万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 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/10410615
• 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; Excretory function; Fiber; Foundations; Glomerular Filtration Rate; Glucose; Goals; Hypertension; Immunosuppression; Inflammation; Inflammation Mediators; Inflammatory; Injury; Kidney; Kidney Diseases; Kidney Failure; Knock-out; Laboratories; Lead; Measures; Mediating; Mediator of activation protein; Modeling; Morbidity - disease rate; Mus; Nephrectomy; Nerve; Pathogenesis; Patients; Pelvis; Perfusion; Population; Proteinuria; Public Health; Rag1 Mouse; 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

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.

摘要 慢性肾脏病（CKD）仍然是一个主要的公共卫生问题，导致严重的发病率 和死亡率的影响。大多数CKD患者使用抗病毒药物治疗。 肾素-血管紧张素系统（RAS）或钠葡萄糖协同转运蛋白2（SGLT 2），但保护 这些代理商提供的服务是不完整的。需要新的治疗方法来大幅推进 CKD患者的护理。在这方面，已知CKD患者的肾神经活动增加 并可导致下游效应，包括高血压、功能降低、蛋白尿， 肾脏疾病进展。肾脏去神经已被证明可以防止这些影响 但大多数临床试验仅包括高血压-CKD患者或排除晚期CKD 患者全部因此，尚不确切知道哪种类型的CKD可以有效治疗。 去肾神经治疗此外，肾感觉传入的相对贡献 和交感传出神经是未知的。我们假设CKD相关的增加 在肾脏炎症中，激活肾感觉神经，进而导致传出神经增加， 神经活动恶化肾功能，CKD进展和高血压。我们的建议 将分析小鼠各种形式CKD期间肾神经的活动， 去神经支配影响疾病进展。我们还将寻找肾神经介质 CKD期间激活。这些新的见解将提供扩大去神经支配的基本原理 研究CKD患者，并更全面地了解肾神经在 CKD的发病机制。