Effect of Renal Nerves on Chronic Kidney Disease

肾神经对慢性肾脏病的影响

• 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
• 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

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 慢性肾脏疾病(CKD)仍然是一个主要的公共卫生问题，导致严重的发病率 以及受影响患者的死亡率。大多数CKD患者使用血管紧张素转换酶抑制剂进行治疗。 肾素-血管紧张素系统(RAS)或钠葡萄糖共转运体2(SGLT2)的保护作用 这些代理商所提供的资金是不完整的。需要新的治疗方法才能大幅进步 CKD患者的护理。在这一点上，已知慢性肾脏病患者肾神经活动增加。 并可能导致下游影响，包括高血压、功能下降、蛋白尿和 肾脏疾病的进展。去肾神经已被证明可以保护肾脏免受这些影响。 但大多数临床试验只包括高血压CKD患者或排除晚期CKD患者。 完全是病人。因此，目前还不清楚哪些类型的慢性肾脏病可以有效地治疗 接受肾去神经治疗。此外，肾感觉神经传入的相对贡献 而交感神经传出神经则不得而知。我们假设与CKD相关的增加 在肾脏中，炎症激活肾感觉神经，进而导致传出神经增加 神经活动使肾功能恶化、慢性肾脏病进展和高血压。我们的建议 将分析在不同形式的CKD小鼠中肾神经的活动，以及 去神经影响疾病的发展。我们还将寻找肾神经的介体。 CKD期间的激活。这些新颖的见解将为扩大去神经作用提供理论基础。 对CKD患者的研究，并更充分地了解肾神经在CKD中的作用 慢性肾脏病的发病机制。