Background Pseudoxanthoma elasticum (PXE) is a genetic disease caused by mutations in the ABCC6 gene that result in low pyrophosphate levels and subsequent progressive soft tissue calcifications. PXE mainly affects the skin, retina, and arteries. However, many patients with PXE experience kidney stones. We determined the prevalence of this pathology in patients with PXE and examined the possible underlying mechanisms in murine models.

Methods We conducted a retrospective study in a large cohort of patients with PXE and analyzed urine samples and kidneys from Abcc6^−/− mice at various ages. We used Yasue staining, scanning electron microscopy, electron microscopy coupled to electron energy loss spectroscopy, and Fourier transform infrared microspectroscopy to characterize kidney calcifications.

Results Among 113 patients with PXE, 45 (40%) had a past medical history of kidney stones. Five of six computed tomography scans performed showed evidence of massive papillary calcifications (Randall plaques). Abcc6^−/− mice spontaneously developed kidney interstitial apatite calcifications with aging. These calcifications appeared specifically at the tip of the papilla and formed Randall plaques similar to those observed in human kidneys. Compared with controls, Abcc6^−/− mice had low urinary excretion of pyrophosphate.

Conclusions The frequency of kidney stones and probably, Randall plaque is extremely high in patients with PXE, and Abcc6^−/− mice provide a new and useful model in which to study Randall plaque formation. Our findings also suggest that pyrophosphate administration should be evaluated for the prevention of Randall plaque and kidney stones.

背景弹性假黄瘤（PXE）是由ABCC6基因突变引起的遗传疾病，导致低的焦磷酸水平和随后的进行性软组织钙化。PXE主要影响皮肤，视网膜和动脉。但是，许多PXE患者会出现肾结石。我们确定了这种病理学在PXE患者中的患病率，并检查了鼠模型中可能的潜在机制。

方法我们对一大批PXE患者进行了回顾性研究，并分析了不同年龄的Abcc6 ^-//-小鼠的尿液样本和肾脏。我们使用Yasue染色，扫描电子显微镜，结合电子能量损失光谱的电子显微镜和傅立叶变换红外光谱来表征肾脏钙化。

结果113例PXE患者中，有45例（40％）有肾结石病史。进行的六次计算机断层扫描中有五次显示大量乳头状钙化（兰德尔斑块）的证据。随着年龄的增长，Abcc6 ^-/-小鼠自发发展出肾间质磷灰石钙化。这些钙化特别地出现在乳头的顶端，并形成类似于在人类肾脏中观察到的兰德尔斑块。与对照组相比，Abcc6 ^-/-小鼠的焦磷酸尿排泄量低。

结论PXE患者肾结石的频率以及可能的Randall斑块的频率非常高，Abcc6 ^-/-小鼠为研究Randall斑块的形成提供了新的有用的模型。我们的发现还表明，应评估焦磷酸盐的施用，以预防兰德尔斑块和肾结石。