Univ. Klinik für Innere Medizin II, Medizinische Universität Wien, Währinger Gürtel 18-20, A-1090, Wien, Austria.
Photon Science, Deutsches Elektronen-Synchrotron (DESY), Notkestr. 85, D-22607 Hamburg, Germany.
Biometals. 2021 Apr;34(2):341-350. doi: 10.1007/s10534-020-00284-8. Epub 2021 Jan 23.
Aims of this study were to investigate gadolinium (Gd) in kidney tissue from a female patient with severe renal failure, who had a magnetic resonance imaging (MRI) with Gd-based contrast agent (GBCA) three times prior to kidney transplantation. Secondly to assess (semi-)quantitatively the Gd concentration in renal tissue and the spatial distribution of Gd in association to suspected co-elements such as calcium (Ca) and zinc (Zn). Archival paraffin embedded kidney tissue was investigated by micro Synchrotron X-ray fluorescence (µSRXRF) at the DORIS III storage ring at beamline L, HASYLAB/DESY(Hamburg, Germany). Elementary gadolinium (Gd) could be demonstrated in a near histological resolution in areas of about 2 × 1.5 mm of size. Mean Gd resulted in 200 ppm with a huge width of distribution (Gd-max: 2000 ppm). In kidney cortex Gd was in-homogeneously, but not randomly, distributed. Gd was verified throughout the investigated tissue. Low Gd was predominately concentrated either in areas with focally atrophic tubules or in areas with totally preserved uriniferous tubes. Moreover, strong correlations existed between Gd and calcium (Ca) or Gd and zinc (Zn) or Gd and strontium (Sr) distribution. Throughout our analysed areas copper (Cu) was nearly homogeneously distributed and Cu association to Gd could not be established, and also not for Gd to Fe. Gd in glomeruli was relatively reduced compared with mean Gd-values, while iron (Fe) distribution clearly demarks glomeruli mostly due to red blood cell iron in these capillary convolutes. Quantitative µSRXRF analysis provided an insight in element spatial distribution of Gd in the renal cortex. The strong correlation of the spatial distribution and associations between elements like Ca, Zn and Sr let us suspect that these elements are involved in the cell metabolism of GBCA. Low Gd in areas with extreme fibrosis and tubule atrophy or in areas with histologically intact tubes, let us suspect that on the one side Gd cannot be transported and deposited into these tissue areas and on the other side we assume that intact renal tubes do not reabsorb and store excreted Gd.
本研究的目的是研究一位患有严重肾衰竭的女性患者的肾脏组织中的钆（Gd），该患者在肾移植前曾三次进行基于钆的造影剂（GBCA）的磁共振成像（MRI）。其次，评估肾脏组织中 Gd 的浓度及其与疑似共存元素（如钙（Ca）和锌（Zn））的空间分布。使用微同步加速器 X 射线荧光（µSRXRF）在德国汉堡的 DORIS III 存储环的 L 光束线上对存档的石蜡包埋肾组织进行了研究。可以在大约 2×1.5mm 大小的区域内以近组织学分辨率证明基本的钆（Gd）。Gd 的平均值为 200ppm，分布范围很宽（Gd-最大值：2000ppm）。在肾皮质中，Gd 分布不均匀，但不是随机分布。在整个研究区域均检测到 Gd。低 Gd 主要集中在局灶性萎缩小管区域或完全保留尿小管的区域。此外，Gd 与钙（Ca）或 Gd 与锌（Zn）或 Gd 与锶（Sr）分布之间存在很强的相关性。在我们分析的区域中，铜（Cu）几乎均匀分布，并且不能确定 Gd 与 Cu 之间的关联，也不能确定 Gd 与 Fe 之间的关联。与平均 Gd 值相比，肾小球中的 Gd 相对减少，而铁（Fe）的分布则明显标志着肾小球，主要是由于这些毛细血管卷曲中的红细胞铁。定量µSRXRF 分析提供了对肾皮质中 Gd 元素空间分布的深入了解。Ca、Zn 和 Sr 等元素的空间分布和相关性的强烈相关性使我们怀疑这些元素参与了 GBCA 的细胞代谢。在极度纤维化和小管萎缩的区域或在组织学上完整的小管区域中低 Gd 的存在，使我们怀疑一方面 Gd 不能被转运并沉积到这些组织区域中，另一方面我们假设完整的肾小管不会再吸收和储存排泄的 Gd。
