Essential characterization of the Randall's plaque-overgrowth interface

每11个美国人中就有1人患有肾结石，最常见的结石是由草酸钙（CaOx）组成的，但目前还没有治疗CaOx肾结石形成早期的方法。最近的证据强烈表明，在结石生长的早期阶段，仅通过Randall 's（间质）斑块（RP）机制在肾脏中保留结石的患者与通过其他机制在肾脏中保留结石的患者具有根本不同的早期结石生长病理。尽管这一途径似乎很常见，但rp中早期结石生长的机制以及这种形式的早期结石生长与其他机制的不同之处尚不清楚，无法指导治疗方法阻止这种最常见的CaOx患者的早期结石生长。目前建议的总体目标是绘制钙石在兰德尔斑块上启动时矿物质和蛋白质的转变。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。

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.