PD04-04 FATTY ACID BINDING PROTEIN 4 DRIVES CALCIFICATION IN THE DEVELOPMENT OF KIDNEY STONE DISEASE (2020)

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I (PD04)1 Apr 2020PD04-04 FATTY ACID BINDING PROTEIN 4 DRIVES CALCIFICATION IN THE DEVELOPMENT OF KIDNEY STONE DISEASE Kazumi Taguchi*, Shuzo Hamamoto, Teruaki Sugino, Misun Kang, Rei Unno, Benjamin Sherer, Manint Usawachintachit, David Tzou, Atsushi Okada, Sunita Ho, Marshall Stoller, Takahiro Yasui, and Thomas Chi Kazumi Taguchi*Kazumi Taguchi* More articles by this author , Shuzo HamamotoShuzo Hamamoto More articles by this author , Teruaki SuginoTeruaki Sugino More articles by this author , Misun KangMisun Kang More articles by this author , Rei UnnoRei Unno More articles by this author , Benjamin ShererBenjamin Sherer More articles by this author , Manint UsawachintachitManint Usawachintachit More articles by this author , David TzouDavid Tzou More articles by this author , Atsushi OkadaAtsushi Okada More articles by this author , Sunita HoSunita Ho More articles by this author , Marshall StollerMarshall Stoller More articles by this author , Takahiro YasuiTakahiro Yasui More articles by this author , and Thomas ChiThomas Chi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000824.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nephrolithiasis 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, associated with a 3-time risk of developing nephrolithiasis. To date, the mechanism by which obesity is linked to stone formation has not been elucidated. We aimed to utilize a transcriptomics approach to discover the missing link between these two epidemic diseases. METHODS: We investigated gene expression profiling of nephrolithiasis patients by two RNA-sequencing approaches: comparison between renal papilla tissue with and without the presence of calcified Randall’s plaques, and comparison between the papilla, medulla, and cortex regions from within a single recurrent stone forming kidney. Results were overlaid between differently expressed genes found in the patient cohort and in the severely lithogenic kidney to identify common genes. We further validated those gene expressions with human kidney samples and a hyperoxaluric nephrolithiasis model mouse and performed the functional analysis using a transgenic mouse. RESULTS: Overlay of these two RNA-sequencing datasets demonstrated there is impairment of lipid metabolism in renal papilla tissue containing Randall’s plaques (Figure 1) linked to downregulation of fatty acid binding protein (FABP) 4. Immunohistochemistry of human kidney specimens and microarray analysis of renal tissue from a nephrolithiasis mouse model confirmed that FABP4 downregulation was associated with renal stone formation. Moreover, a knockout mouse study demonstrated that FABP4 deficiency caused significantly larger amount of both renal and urinary crystals compared with the wildtype phenotype (Figure 2). CONCLUSIONS: Our study revealed that FABP4 plays an important, previously unrecognized role in kidney stone formation, providing a feasible mechanism to explain the link between nephrolithiasis and metabolic syndrome. Source of Funding: NIH (K12-DK-07-006, P20-DK-116193, P20-DK-100863).JSPS (#16K11054). © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e79-e80 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazumi Taguchi* More articles by this author Shuzo Hamamoto More articles by this author Teruaki Sugino More articles by this author Misun Kang More articles by this author Rei Unno More articles by this author Benjamin Sherer More articles by this author Manint Usawachintachit More articles by this author David Tzou More articles by this author Atsushi Okada More articles by this author Sunita Ho More articles by this author Marshall Stoller More articles by this author Takahiro Yasui More articles by this author Thomas Chi More articles by this author Expand All Advertisement PDF downloadLoading ...