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）： 慢性肾病（CKD）是大多数终末期肾衰竭的先兆，也是心血管疾病的潜在危险因素。最近对 CKD 的兴趣集中在 CKD 病程后期发生的结构变化过程，即功能性肾脏被疤痕组织取代。我们认为这些过程最初是植根于生理学的适应性机制，旨在补偿早期的损伤，然后因为控制它们的手段丧失而出错。本研究的总体目的是通过在早期 CKD 标准模型（即大鼠肾次全切除术 (STN)）中应用肾脏微穿刺方法，研究 CKD 早期肾脏生理学的主要特征。我们发现，在 STN 后的第一周内给大鼠喂食高氯化钠饮食会导致逆转 肾小球反馈（TGF）反应从负增益到正增益。虽然这将加速恢复盐平衡，但也意味着肾脏愿意放弃 TGF 通常赋予的功能和血流动力学稳定性。这种向异常 TGF 的转变在膳食盐摄入量和肾小球毛细血管壁动态拉伸松弛之间建立了正相关关系，这可能解释了膳食盐对 CKD 的有害影响。即将进行的研究将确定这种生理学在适应肾单位损失的早期阶段是否仍然相关，它是否是一个在高 NaCl 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。

项目成果

Comparative Decomposition of Humans and Pigs: Soil Biogeochemistry, Microbial Activity and Metabolomic Profiles.

人类和猪的比较分解：土壤生物地球化学、微生物活性和代谢组学特征。

• 发表时间: 2020
• 作者: DeBruyn, Jennifer M;Hoeland, Katharina M;Taylor, Lois S;Stevens, Jessica D;Moats, Michelle A;Bandopadhyay, Sreejata;Dearth, Stephen P;Castro, Hector F;Hewitt, Kaitlin K;Campagna, Shawn R;Dautartas, Angela M;Vidoli, Giovanna M;Mundorff, Amy Z
• 通讯作者: Mundorff, Amy Z