Essential characterization of the Randall's plaque-overgrowth interface

兰德尔斑块过度生长界面的基本特征

• 批准号: 10373023
• 负责人: JAMES C WILLIAMS
• 金额: $ 23.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373023
• 关键词: 3-Dimensional; American; Automobile Driving; Benign; Calcium Oxalate; Characteristics; Collection; Data; Deposition; Disease; Dissection; Duct (organ) structure; Event; Female; Fluorescence; Foundations; Future; Goals; Growth; Health Care Costs; Histologic; In Situ; Kidney; Kidney Calculi; Kidney Papilla; Label; Lasers; Learning; Light; Maps; Mass Spectrum Analysis; Methods; Microdissection; Microscopy; Minerals; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Persons; Pharmacologic Substance; Phase; Proteins; Proteome; Set protein; Site; Structure; Sum; Symptoms; Testing; Time; Urine; Work; base; calcification; common treatment; effective therapy; infrared microscopy; interstitial; kidney interstitial tissue; male; metabolic profile; microCT; mineralization; multiphoton imaging; prevent; sex; therapy development

Kidney stones afflict about 1 in 11 Americans and the most common stones are composed of calcium oxalate (CaOx), but no therapies exist to treat CaOx kidney stone formation at its earliest stages. Recent evidence strongly suggests that patients who retain stones in their kidneys during the earliest phase of stone growth solely via the mechanism of Randall’s (interstitial) plaque (RP) have a fundamentally different pathology of early stone growth than do those patients who retain stones in the kidney via other mechanisms. In spite of how common this pathway seems to be, the mechanism by which early stone growth proceeds on RP—and how this form of early stone growth may be different from other mechanisms—is not understood well enough to direct therapies toward blocking the growth of early stones in this most-common of CaOx patients. The overall objective for the present proposal is to map the mineral and protein transitions as CaOx stones initiate on Randall’s plaque. The work proposed here is foundational for learning how to block the genesis of these stones, and thus to provide treatment to prevent stones from forming on Randall’s plaques.

肾结石困扰约1/11的美国人，最常见的结石是由草酸钙（CaOx）组成，但没有治疗方法可以在其最早阶段治疗CaOx肾结石形成。最近的证据有力地表明，在结石生长的最早阶段仅通过兰德尔（间质）斑块（RP）机制将结石保留在肾脏中的患者与通过其他机制将结石保留在肾脏中的患者相比，具有根本不同的早期结石生长病理学。尽管这种途径似乎是多么常见，早期结石生长在RP上进行的机制以及这种形式的早期结石生长如何与其他机制不同还没有得到足够的理解，以指导治疗方法阻止这种最常见的CaOx患者的早期结石生长。本提案的总体目标是绘制矿物质和蛋白质的转变，因为CaOx结石在Randall斑块上启动。这里提出的工作是学习如何阻止这些结石的发生的基础，从而提供治疗，以防止结石在兰德尔斑块上形成。