Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Urolithiasis. 2021 Apr;49(2):123-135. doi: 10.1007/s00240-020-01216-4. Epub 2020 Oct 7.
Kidney stones frequently develop as an overgrowth on Randall's plaque (RP) which is formed in the papillary interstitium. The organic composition of RP is distinct from stone matrix in that RP contains fibrillar collagen; RP in tissue has also been shown to have two proteins that are also found in stones, but otherwise the molecular constituents of RP are unstudied. We hypothesized that RP contains unique organic molecules that can be differentiated from the stone overgrowth by fluorescence. To test this, we used micro-CT-guided polishing to expose the interior of kidney stones for multimodal imaging with multiphoton, confocal and infrared microscopy. We detected a blue autofluorescence signature unique to RP, the specificity of which was also confirmed in papillary tissue from patients with stone disease. High-resolution mineral mapping of the stone also showed a transition from the apatite within RP to the calcium oxalate in the overgrowth, demonstrating the molecular and spatial transition from the tissue to the urine. This work provides a systematic and practical approach to uncover specific fluorescence signatures which correlate with mineral type, verifies previous observations regarding mineral overgrowth onto RP and identifies a novel autofluorescence signature of RP demonstrating RP's unique molecular composition.
肾结石经常在 Randall 斑块 (RP) 上过度生长而形成,RP 形成于乳头间质中。RP 的有机成分与结石基质明显不同,RP 含有纤维状胶原蛋白;组织中的 RP 还含有两种也存在于结石中的蛋白质,但 RP 的分子成分尚未得到研究。我们假设 RP 含有独特的有机分子,可以通过荧光从结石过度生长中区分出来。为了验证这一点,我们使用微 CT 引导的抛光技术来暴露肾结石的内部,以便进行多光子、共聚焦和红外显微镜的多模态成像。我们检测到了一种独特的 RP 自发荧光特征,其特异性在结石病患者的乳头状组织中也得到了证实。对结石的高分辨率矿物映射也显示了从 RP 中的磷灰石到过度生长中的草酸钙的转变,证明了从组织到尿液的分子和空间转变。这项工作提供了一种系统和实用的方法来揭示与矿物类型相关的特定荧光特征,验证了先前关于 RP 上矿物过度生长的观察结果,并确定了 RP 的一种新的自发荧光特征,证明了 RP 的独特分子组成。