ABCC6 缺乏促进 Randall 斑块的形成。
ABCC6 Deficiency Promotes Development of Randall Plaque.
机构信息
Unité Mixte de Recherche S 1155, Sorbonne Universités, Université Pierre et Marie Curie-Paris 06, Paris, France;
Unité Mixte de Recherche S 1155, Institut National de la Santé et de la Recherche Médicale, Paris, France.
出版信息
J Am Soc Nephrol. 2018 Sep;29(9):2337-2347. doi: 10.1681/ASN.2017101148. Epub 2018 Jul 10.
BACKGROUND
Pseudoxanthoma elasticum (PXE) is a genetic disease caused by mutations in the 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 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). 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, 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 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
弹力假黄瘤（PXE）是一种由基因 突变引起的遗传性疾病，导致焦磷酸盐水平降低，随后进行性软组织钙化。PXE 主要影响皮肤、视网膜和动脉。然而，许多 PXE 患者会出现肾结石。我们确定了 PXE 患者中这种病理的患病率，并在小鼠模型中研究了潜在的机制。
方法
我们对一大群 PXE 患者进行了回顾性研究，并分析了不同年龄的小鼠尿液样本和肾脏。我们使用 Yasue 染色、扫描电子显微镜、电子显微镜结合电子能量损失光谱和傅里叶变换红外微光谱来表征肾脏钙化。
结果
在 113 名 PXE 患者中，有 45 名（40%）有肾结石的既往病史。六次进行的计算机断层扫描中有五次显示出大量乳突钙化（Randall 斑块）的证据。随着年龄的增长，小鼠自发地出现肾脏间质磷灰石钙化。这些钙化仅出现在乳突尖端，并形成类似于在人类肾脏中观察到的 Randall 斑块。与对照组相比，小鼠的尿液中焦磷酸盐排泄量较低。
结论
肾结石的频率，可能还有 Randall 斑块，在 PXE 患者中极高，而小鼠为研究 Randall 斑块形成提供了一种新的有用模型。我们的发现还表明，应评估焦磷酸盐的给药以预防 Randall 斑块和肾结石。
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