Abstracts EAU20 Virtual Congress and Theme Week

244 Fatty acid binding protein 4 drives calcium oxalate crystallization in the development of
kidney stone disease

Eur Urol Open Sci 2020;19(Suppl 2):e430

Taguchi K.1, Hamamoto S.1, Sugino T.1, Kawase K.1, Unno R.1, Okada A.1, Stoller M.L.2, Chi T.2, Yasui T.1

1
Nagoya City University Graduate School of Medical Sciences, Dept. of Nephro-Urology, Nagoya, Japan, 2University of California, San Francisco,
Dept. of Urology, San Francisco, United States of America

Introduction & Objectives: Kidney stone disease (KSD) is a significant source of morbidity, and its incidence has increased significantly over the
last decades. This rise has been attributed to concurrent increasing rates of obesity. To date, the mechanism by which obesity is linked to stone
formation has not been elucidated. We previously reported that fatty acid binding protein (FABP) 4 was associated with Randall’s plaques (RP)
formation which was proven by a transcriptomics approach of KSD patients. Therefore, we validated FABP4 expression and analyzed its function
with a transgenic mouse in order to elucidate the role of this gene on stone development.

Materials & Methods: 1) In an IRB-approved study, we performed immunohistochemistry of FABP4 for kidney tissues containing RP which were
collected from radical nephrectomy specimens. RP was confirmed by micro-CT to determine the area used for immunohistochemistry. In addition, a
nephrocalcinosis model mouse administered glyoxylate for 12 days to induce hyperoxaluric state were examined for confirming Fabp4 expression.
2) We compared renal and urinary crystal development between the Fabp4 knockout (KO) and wildtype (WT) mice using the technique for
a nephrocalcinosis model mouse. The expression levels of stone-, lipid-, and inflammatory-related genes were examined by PCR to further
investigate the role of Fabp4 on KSD.

Results: 1) Both tubular epithelial and interstitial cells in the human kidney confirmed FABP4 expression in the cortex whereas only tubular
epithelial cells expressed FABP4 in the papilla and medulla. In addition, fewer FABP4 positive collecting duct cells were present in papilla with RP
present. The nephrocalcinosis model mouse showed that Fabp4 expression levels decreased until day 6, which negatively correlated to the amount
of renal crystal deposits seen by staining.
2) The Fabp4 KO mice had significantly larger amount of renal crystal deposits and urinary crystal than the WT mice did. Additionally, the gene
expression level of C-C motif chemokine 2 was lower in the Fabp4 KO mice than that in the WT mice, suggesting that Fabp4 impairment linked to
decrease of immune-response may result in stone formation. (Figure 1)

Eur Urol Open Sci 2020;19(Suppl 2):e430

Abstracts EAU20 Virtual Congress and Theme Week

Conclusions: Our results revealed that FABP4 appears to be a key molecule facilitating KSD and may prove to be a therapeutic target for their
prevention.

Eur Urol Open Sci 2020;19(Suppl 2):e431