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

Stan Benjamens,Marian L C Bulthuis,Cyril Moers,Jan-Luuk Hillebrands,Ines F Antunes,Stefan P Berger,Riemer H J A Slart,Robert A Pol,Martin H De Borst,Melanie Reijrink

doi:10.1038/s41598-021-81144-4

Stan Benjamens, Marian L C Bulthuis + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-81144-4

Copy DOI

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.

Highlights

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
Uptake of [18F]-NaF correlated stronger with Alizarin red staining for active microcalcifications compared to Von Kossa staining of consolidated calcifications, suggesting a role for [18F]-NaF imaging in the identification of early stage areas of nephrocalcinosis
The presented samples represent a case mix of donor kidneys and explanted kidney allografts. These two sample types differed with regard to tracer binding, with more [ 18F]-NaF uptake observed in explanted kidney allograft samples

Summary

Introduction

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. 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. Studies focusing on kidney allograft biopsies within one-year after transplantation demonstrated an association between the early presence of calcium depositions and both inferior graft function and poor graft survival[4,8,9] Whether these microcalcifications play an active role in allograft dysfunction or are merely indicators of deregulated mineral metabolism remains unclear. The results of several prospective clinical studies showed that early vascular [18F]-NaF activity relates well to both macrocalcifications, detected by CT imaging, and more interestingly, the increase in size of these c alcifications[18,19,20]

Methods

Results

Conclusion