Homeostasis and Tubuloglomerular Feedback

稳态和肾小球反馈

• 批准号: 9275299
• 负责人: SCOTT Culver THOMSON
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9275299
• 关键词: Affect; Body Fluids; Cardiovascular Diseases; Chronic Kidney Failure; Cicatrix; Communication; Data; Deductibles; Diet; End stage renal failure; Engineering; Equilibrium; Event; Exposure to; Feedback; Flowmetry; Funding; Future; Glomerular Capillary; Goals; Grant; Homeostasis; Injury; Juxtaglomerular Apparatus; Kidney; Kidney Diseases; Logic; Maps; Metabolic; Methods; Micropuncture; Mission; Modeling; Modus; N-Methyl-D-Aspartate Receptors; Nephrectomy; Nephrons; Nitric Oxide; Patient Care; Patients; Physiology; Plant Roots; Process; Rattus; Records; Regulation; Relaxation; Renal Blood Flow; Renal function; Research; Role; Sentinel; Series; Signal Transduction; Speed; Stretching; System; Time; Tissues; Tubular formation; Ursidae Family; Veterans; Work; cardiovascular risk factor; career development; clinically relevant; control theory; cost; design; dietary salt; experimental study; feeding; glomerular filtration; glomerular function; hemodynamics; high salt diet; improved; in vivo; interest; kidney metabolism; novel; public health relevance; response; salt balance; salt intake; tool

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is the precursor to most end-stage renal failure and is a potent risk factor for cardiovascular disease. Recent interest in CKD has focused on processes of structural change that occur later in the course of CKD when functioning kidney is replaced by scar tissue. We ascribe to the view that these processes begin as adaptive mechanisms, rooted in physiology, to compensate for an earlier injury, then go awry because the means to control them is lost. It is the general purpose of the proposed research to investigate cardinal features of kidney physiology early in the course of CKD by applying renal micropuncture methods in a standard model for early CKD, namely subtotal nephrectomy (STN) in the rat. We have discovered that feeding high NaCl diet to a rat during the first week after STN leads to a reversal of the tubuloglomerular feedback (TGF) response from negative to positive gain. While this will speed up the return to salt balance, it also signifies that the kidney is willing to forego the functional and hemodynamic stability normally conferred by TGF. This shift to anomalous TGF establishes a positive relationship between dietary salt intake and dynamic stretch-relaxation of the glomerular capillary wall, which may explain the nefarious effect of dietary salt in CKD. The upcoming research will determine whether this physiology remains relevant beyond the early stages of adaptation to nephron loss, whether it is a durable process that persists after high NaCl is withdrawn, whether it depends on Na, Cl, or both, and how it interacts with kidney metabolism.

描述(由申请人提供)： 慢性肾脏疾病(CKD)是大多数终末期肾功能衰竭的先兆，也是心血管疾病的潜在危险因素。最近对CKD的兴趣主要集中在CKD过程中后期发生的结构变化过程，即功能肾被疤痕组织取代。我们认为，这些过程最初是一种适应机制，植根于生理，以补偿早期的伤害，然后因为失去了控制它们的手段而出错。本研究的主要目的是在大鼠肾大部切除术(STN)的早期标准模型上应用肾脏微穿刺法，研究CKD早期肾脏生理的基本特征。我们发现，在STN后的第一周，给大鼠喂食高盐饮食会导致反转 肾小管小球反馈(TGF)反应由负转正。虽然这将加速盐平衡的恢复，但这也意味着肾脏愿意放弃通常由转化生长因子赋予的功能和血流动力学稳定性。这种向异常转化生长因子的转变建立了饮食盐摄入量与肾小球毛细血管壁动态拉伸-松弛之间的正相关关系，这可能解释了饮食盐在CKD中的恶毒作用。即将到来的研究将确定这种生理学是否在适应肾单位丢失的早期阶段后仍然相关，它是否是一个在高盐停用后持续存在的持久过程，它是否依赖于钠、氯或两者，以及它如何与肾脏代谢相互作用。