A continuum of mineralization from human renal pyramid to stones on stems.
A continuum of mineralization from human renal pyramid to stones on stems.
复制标题
从人类肾金字塔到茎上的石头的矿化连续体。
DOI：
10.1016/j.actbio.2018.01.040
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发表时间：
2018
影响因子：
9.7
通讯作者：
Ho,SunitaP
中科院分区：
文献类型：
--
作者：
Sherer,BenjaminA;Chen,Ling;Kang,Misun;Shimotake,AlexR;Wiener,ScottV;Chi,Tom;Stoller,MarshallL;Ho,SunitaP
预防肾结石的新方法的发展取决于对肾锥体内矿化进程的了解。从肾锥体内的小块矿化体积发展到较大的间质斑块，最终导致临床上可检测到的磷酸钙茎上的钙基结石，将通过相关的显微镜方法呈现。采用高分辨率X射线计算机断层扫描(MICRICO-XCT)、电子显微镜和能量色散X射线(EDX)对间质斑块、骨柄和附着结石进行成分分析。矿化程度越严重，矿化密度越高，在成熟的兰德尔斑块和肾结石附着的茎中检测到的矿化密度最高。EDX分析显示，间质斑块、茎和结石中的元素组成各不相同。显微XCT对结石茎内未闭塞的小管进行重建，其平均管径与Henle的细肢、血管和集合管相对应。相关显微镜证实，导致钙基肾结石的矿化进展通过涉及四个解剖和结构上不同的生物矿化区域的连续体发生：1)肾锥体内近端肾小管内矿化；2)乳头尖端附近的间质兰德尔斑块；3)出现斑块(茎)；以及4)异质结石的身体。最常见的结石类型是草酸钙，已知形成在肾乳头上的一种被称为兰德尔斑块的磷酸钙沉积物上。新的成像技术已经确定了不同的生物矿化区域，不仅在顶端，而且在整个肾乳头。对兰德尔斑块形成的经典理解是使用相关成像技术重新形成的。这项研究建立了解剖学上特定生物矿化事件的逐步进展，包括：1)肾锥体内近端肾小管内矿化；2)乳头尖端附近的间质Randall斑块；3)显露的斑块(茎)；以及4)异质结石的身体，并对是否需要进行看似合理的部位特异性治疗干预提供了见解。
The development of new modalities for kidney stone prevention rests upon understanding the progression of mineralization within the renal pyramid. The progression from small foci of mineralized volumes within the renal pyramid to larger interstitial plaques that ultimately lead into clinically detectable calcium-based stones on calcium phosphate stems will be presented through correlative microscopy approach. High resolution X-ray computed tomography (micro-XCT), electron microscopy, and energy dispersive X-ray (EDX) compositional analyses of interstitial plaques, stems, and attached stones were performed. Increase in mineral density progressed with mineralization severity, with the highest mineral densities detected within mature Randall’s plaque and stems to which kidney stones were attached. EDX analyses revealed variable elemental composition within interstitial plaque, stems, and stones. Micro-XCT reconstructions of stones with stems enabled visualization of unoccluded tubules within stems, with average tubule diameters corresponding to thin limbs of Henle, blood vessels, and collecting ducts. Correlative microscopy confirmed that the progression of mineralization leading to calcium-based nephrolithiasis occurs through a continuum involving four anatomically and structurally distinct biomineralization regions: 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall’s plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones.Statement of SignificanceNephrolithiasis is a common condition affecting nearly 1 in 11 Americans. The most common type of stone, calcium oxalate is known to form on a calcium phosphate deposit on the renal papilla known as Randall’s plaque. Novel imaging techniques have identified distinct regions of biomineralization not just at the tip, but throughout the renal papilla. The classic understanding of Randall’s plaque formation is reformulated using correlative imaging techniques. This study establishes a stepwise progression of anatomically-specific biomineralization events including, 1) proximal intratubular mineralization within the renal pyramid; 2) interstitial Randall’s plaque near the tip of the papilla; 3) emerging plaque (stems); and, 4) the body of heterogeneous stones, and provides insights into the need for plausible site-specific therapeutic intervention.