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.

抽象的 慢性肾脏病（CKD）仍然是一个导致严重发病率的主要公共卫生问题 和受影响患者的死亡率。大多数 CKD 患者均接受抑制剂治疗 肾素-血管紧张素系统 (RAS) 或钠葡萄糖协同转运蛋白 2 (SGLT2) 但保护作用 这些代理提供的服务是不完整的。需要新的治疗方法才能取得实质性进展 CKD 患者的护理。在这方面，已知 CKD 中肾神经活动增加 并可能导致下游影响，包括高血压、功能下降、蛋白尿和 肾脏疾病进展。去肾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 完全是病人。因此，尚不清楚哪些类型的 CKD 可以有效治疗 采用肾去神经术治疗。此外，肾感觉传入的相对贡献 和交感传出神经尚不清楚。我们假设 CKD 相关的增加 肾脏炎症会激活肾脏感觉神经，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的 CKD 期间肾神经的活动以及是否 去神经支配影响疾病进展。我们还将寻找肾神经的介质 CKD 期间激活。这些新颖的见解将为扩大去神经支配提供理论依据 对 CKD 患者进行研究，更全面地了解肾神经在 CKD 的发病机制。