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. 2021 Jan 19;11(1):1841.
doi: 10.1038/s41598-021-81144-4.

[18F]-sodium fluoride autoradiography imaging of nephrocalcinosis in donor kidneys and explanted kidney allografts

Stan Benjamens  1   2 , Ines F Antunes  3 , Jan-Luuk Hillebrands  4 , Melanie Reijrink  5 , Marian L C Bulthuis  4 , Stefan P Berger  6 , Cyril Moers  7 , Martin H de Borst  6 , Riemer H J A Slart  3   8 , Robert A Pol  7
Affiliations

[18F]-sodium fluoride autoradiography imaging of nephrocalcinosis in donor kidneys and explanted kidney allografts

Stan Benjamens et al. Sci Rep. .

Abstract

Nephrocalcinosis is present in up to 43% of kidney allograft biopsies at one-year after transplantation and is associated with inferior graft function and poor graft survival. We studied [18F]-sodium fluoride ([18F]-NaF) imaging of microcalcifications in donor kidneys (n = 7) and explanted kidney allografts (n = 13). Three µm paraffin-embedded serial sections were used for histological evaluation of calcification (Alizarin Red; Von Kossa staining) and ex-vivo [18F]-NaF autoradiography. The images were fused to evaluate if microcalcification areas corresponded with [18F]-NaF uptake areas. Based on histological analyses, tubulointerstitial and glomerular microcalcifications were present in 19/20 and 7/20 samples, respectively. Using autoradiography, [18F]-NaF uptake was found in 19/20 samples, with significantly more tracer activity in kidney allograft compared to deceased donor kidney samples (p = 0.019). Alizarin Red staining of active microcalcifications demonstrated good correlation (Spearman's rho of 0.81, p < 0.001) and Von Kossa staining of consolidated calcifications demonstrated significant but weak correlation (0.62, p = 0.003) with [18F]-NaF activity. This correlation between ex-vivo [18F]-NaF uptake and histology-proven microcalcifications, is the first step towards an imaging method to identify microcalcifications in active nephrocalcinosis. This may lead to better understanding of the etiology of microcalcifications and its impact on kidney transplant function.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Autoradiography image of [18F]-sodium fluoride ([18F]-NaF) uptake (A), with the overlay image of [18F]-NaF uptake with Alizarin red staining of microcalcifications (B) and Von Kossa staining of calcifications (C).
Figure 2
Figure 2
Overlay image of [18F]-sodium fluoride ([18F]-NaF) uptake and (Alizarin red) microcalcifications (A), with Alizarin red staining for microcalcifications (B) and Von Kossa staining for calcifications (C).
Figure 3
Figure 3
Correlation of the number of [18F]-sodium fluoride ([18F]-NaF) areas with Alizarin red stained microcalcifications (A) and Von Kossa stained calcifications (B).
Figure 4
Figure 4
Differences between two groups, ≤ 5% and > 5% [18F]-sodium fluoride ([18F]-NaF) tracer surface area, for the number of Alizarin red stained microcalcifications (A) and Von Kossa stained calcifications (B) (median, interquartile range).
See this image and copyright information in PMC

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