Gadolinium distribution in kidney tissue determined and quantified by micro synchrotron X-ray fluorescence

Abstract

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 mm² 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.

Keywords: Calcium; Gadolinium; Kidney; Strontium; Synchrotron X-ray fluorescence; Zinc.