Homeostasis and Tubuloglomerular Feedback

稳态和肾小球反馈

• 批准号: 8632719
• 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 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8632719
• 关键词: Affect; Body Fluids; Cardiovascular Diseases; Chronic Kidney Failure; Cicatrix; Communication; Data; Diet; End stage renal failure; Engineering; Equilibrium; Event; Exposure to; Feedback; Flowmetry; Funding; Future; Glomerular Capillary; Goals; Grant; Homeostasis; Injury; Juxtaglomerular Apparatus; Kidney; 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; Risk Factors; Role; Sentinel; Series; Signal Transduction; Sodium Chloride; Speed; Staging; Stretching; System; Time; Tissues; Tubular formation; Ursidae Family; Veterans; Work; career development; clinically relevant; design; feeding; glomerular filtration; glomerular function; hemodynamics; improved; in vivo; interest; kidney metabolism; novel; public health relevance; research study; response; salt balance; salt intake; theories; tool

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.

慢性肾病 (CKD) 是大多数终末期肾衰竭的先兆，也是导致肾衰竭的潜在危险因素。 心血管疾病。最近对 CKD 的兴趣集中在随后发生的结构变化过程上。 当功能性肾脏被疤痕组织取代时，CKD 的病程。我们认为这些 过程开始于根植于生理学的适应性机制，以补偿早期的损伤，然后继续 错误是因为失去了控制它们的手段。拟议研究的一般目的是调查 应用肾微穿刺方法研究 CKD 病程早期肾脏生理学的主要特征 早期 CKD 的标准模型，即大鼠肾次全切除术 (STN)。我们发现 STN 后第一周给大鼠喂食高 NaCl 饮食会导致肾小管肾小球功能逆转 从负增益到正增益的反馈（TGF）反应。虽然这会加速恢复盐平衡，但 也意味着肾脏愿意放弃通常赋予的功能和血流动力学稳定性 通过转化生长因子。这种向异常 TGF 的转变在膳食盐摄入量和 TGF 之间建立了正相关关系。 肾小球毛细血管壁的动态拉伸-松弛，这可以解释饮食的不良影响 CKD 中的盐。即将进行的研究将确定这种生理学在早期研究之后是否仍然具有相关性。 适应肾单位损失的阶段，是否是一个在高氯化钠撤除后持续存在的持久过程， 它是否取决于 Na、Cl 或两者，以及它如何与肾脏代谢相互作用。