Clinical Pathophysiology of Nephrolithiasis

总结 该项目的广泛目标是了解结石病的两种常见治疗方法的影响 肾钙（Ca）处理，以及肾生理学和结石组织钙化之间的联系 前体（SF）。结石形成需要尿过饱和（SS）与草酸钙（CaOx）和钙 高钙尿症（IH）是SS增加的常见原因。预防结石 复发依赖于SS的降低，但在特定患者中实现这一点的最佳方法尚不清楚。 近端和远端肾单位肾小管钙重吸收（rCa）减少是IH的特征。我们 假设肾小管转运改变与发现的组织钙化的发病机制有关 在SF，以及他们的结石，并建议研究钙SF与IH（IHSF）谁经历了乳头状 在内窥镜检查期间进行标测，将选择两种乳头外观之一：1）乳头， 丰富的菌斑但无堵塞（典型的许多CaOx SF）或2）具有适度菌斑的堵塞（典型的磷灰石 SF）。我们将检验斑块表面积与近端小管rCa降低相关的假设， 栓塞面积与CaP SS增加相关（Aim 1.1a，b）。在证明了IHSF和 正常人（N）的rCa在一个稳定的饮食，空腹和进食，我们建议探索这些发现，使用高， 低钠摄入，有或没有柠檬酸钾。我们将研究空腹、进食和过夜（高风险）对rCa的影响。 结石形成期），使用锂清除率和尿结石风险因素（目的1.2a、1.4a、1.5）。到 了解我们预期的低钠饮食和柠檬酸钾的rCa变化机制，我们将 测量近端和远端肾单位转运蛋白的尿外泌体（目的1.2b、1.4和1.5）。SS和 将测量亚稳态的上限，以更好地了解柠檬酸钾和低钠饮食 影响这些重要的治疗参数（目标1.5，1.6）。为了进一步了解斑块和栓塞， 形成炎症的作用（目的1.3）。

Summary The project's broad objective is an understanding of the impact of two common treatments for stone disease on renal calcium (Ca) handling, and the links between renal physiology and tissue calcifications in stone formers (SF). Stone formation requires urine supersaturation (SS) with calcium oxalate (CaOx) and calcium phosphate (CaP); idiopathic hypercalciuria (IH) is a common cause of increased SS. Prevention of stone recurrence relies on decreasing SS, but the optimal means of doing this in a given patient is not clear. Decreased tubular Ca reabsorption (rCa), in both proximal and distal nephron, is characteristic of IH. We hypothesize that renal tubule transport alterations are linked to pathogenesis of the tissue calcifications found in SF, as well as to their stones, and propose to study Ca SF with IH (IHSF) who have undergone papillary mapping during endoscopy who will be selected for one of two papillary appearances: 1) papillae with abundant plaque but no plugging (typical of many CaOx SF) or 2) plugs with modest plaque (typical of apatite SF). We will test the hypothesis that plaque surface area correlates with decreased proximal tubule rCa, and plug area correlates with increased CaP SS (Aim 1.1a,b). Having demonstrated differences between IHSF and normals (N) in rCa on a stable diet, both fasting and fed, we propose to explore these findings using high and low Na intake, with or without Kcitrate. We will study the effects on rCa, fasting, fed and overnight (a high risk period for stone formation), using lithium clearance and urine stone risk factors (Aims 1.2a, 1.4a, 1.5). To understand the mechanisms of the changes in rCa that we expect with low Na diet and K citrate, we will measure urine exosomes for both proximal and distal nephron transporters (Aims 1.2b, 1.4, and 1.5). SS and upper limit of metastability will be measured to gain a better understanding of how K citrate and low Na diet affects these important treatment parameters (Aim 1.5, 1.6). To gain further insight into plaque and plug formation the role of inflammation (Aim 1.3).