Homeostasis and Tubuloglomerular Feedback

慢性肾脏病（CKD）是大多数终末期肾衰竭的前兆，是慢性肾脏病的潜在危险因素。 心血管疾病最近对CKD的兴趣集中在后期发生的结构变化过程， CKD的过程中，功能正常的肾脏被疤痕组织取代。我们认为， 这些过程开始是一种适应机制，植根于生理学，以补偿早期的损伤，然后 因为失去了控制它们的手段。本研究的总体目的是调查 应用肾脏微穿刺方法，观察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（CKD）。我们发现 大鼠在断奶后的第一周内喂食高NaCl饮食，导致肾小管肾小球的逆转， 反馈（TGF）响应从负增益到正增益。虽然这将加速恢复盐平衡， 也意味着肾脏愿意放弃通常赋予的功能和血液动力学稳定性 通过TGF。这种向异常TGF的转变建立了膳食盐摄入量与 肾小球毛细血管壁的动态拉伸-松弛，这可能解释了饮食的邪恶作用。 CKD中的盐。即将进行的研究将确定这种生理学是否在早期之后仍然相关。 对肾单位丧失的适应阶段，它是否是一个持续的过程，在高NaCl被撤回后仍然存在， 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。

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beyond the early stages of adaptation to nephron loss, whether it is a durable process that persists after high NaCl is withdrawn, whether it depends on Na, Cl, or both, and how it interacts with kidney metabolism.