Urinary extracellular vesicles signature for diagnosis of kidney disease

Keiichi Takizawa; Koji Ueda; Masahiro Sekiguchi; Eiji Nakano; Tatsuya Nishimura; Yuko Kajiho; Shoichiro Kanda; Kenichiro Miura; Motoshi Hattori; Junya Hashimoto; Yuko Hamasaki; Masataka Hisano; Tae Omori; Takayuki Okamoto; Hirotsugu Kitayama; Naoya Fujita; Hiromi Kuramochi; Takanori Ichiki; Akira Oka; Yutaka Harita

doi:10.1016/j.isci.2022.105416

Urinary extracellular vesicles signature for diagnosis of kidney disease

iScience. 2022 Nov 8;25(11):105416. doi: 10.1016/j.isci.2022.105416. eCollection 2022 Nov 18.

Authors

Keiichi Takizawa¹, Koji Ueda², Masahiro Sekiguchi¹, Eiji Nakano¹, Tatsuya Nishimura¹, Yuko Kajiho¹, Shoichiro Kanda¹, Kenichiro Miura³, Motoshi Hattori³, Junya Hashimoto⁴, Yuko Hamasaki⁴, Masataka Hisano⁵, Tae Omori⁶, Takayuki Okamoto⁷, Hirotsugu Kitayama⁸, Naoya Fujita⁹, Hiromi Kuramochi¹⁰, Takanori Ichiki¹⁰, Akira Oka¹, Yutaka Harita¹

Affiliations

¹ Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
² Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
³ Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
⁴ Department of Nephrology, Faculty of Medicine, Toho University, Tokyo 143-8541, Japan.
⁵ Department of Nephrology, Chiba Children's Hospital, Chiba 266-0007, Japan.
⁶ Department of Pediatrics, Tokyo Metropolitan Bokutoh Hospital, Tokyo 130-8575, Japan.
⁷ Department of Pediatrics, Hokkaido University Graduate School of Medicine, Hokkaido 060-8648, Japan.
⁸ Department of Nephrology, Shizuoka Children's Hospital, Shizuoka, 420-8660, Japan.
⁹ Department of Nephrology, Aichi Children's Health and Medical Center, Aichi 474-8710, Japan.
¹⁰ Department of Materials Engineering, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.

Abstract

Congenital disorders characterized by the quantitative and qualitative reduction in the number of functional nephrons are the primary cause of chronic kidney disease (CKD) in children. We aimed to describe the alteration of urinary extracellular vesicles (uEVs) associated with decreased renal function during childhood. By nanoparticle tracking analysis and quantitative proteomics, we identified differentially expressed proteins in uEVs in bilateral renal hypoplasia, which is characterized by a congenitally reduced number of nephrons. This expression signature of uEVs reflected decreased renal function in CKD patients by congenital anomalies of the kidney and urinary tract or ciliopathy. As a proof-of-concept, we constructed a prototype ELISA system that enabled the isolation of uEVs and quantitation of expression of molecules representing the signature. The system identified decreased renal function even in its early stage. The uEVs signature could pave the way for non-invasive methods that can complement existing testing methods for diagnosing kidney diseases.

Keywords: Biomolecules; Health sciences; Nephrology.