Urinary Exosomal mRNA of WT1 as Diagnostic and Prognostic Biomarker for Diabetic Nephropathy

Hideharu Abe; Akiko Sakurai; Hiroyuki Ono; Sanae Hayashi; Sakiya Yoshimoto; Arisa Ochi; Sayo Ueda; Kenji Nishimura; Eriko Shibata; Masanori Tamaki; Fumi Kishi; Seiji Kishi; Taichi Murakami; Kojiro Nagai; Toshio Doi

doi:10.2152/jmi.65.208

Hideharu Abe, Akiko Sakurai, Hiroyuki Ono, Sanae Hayashi, Sakiya Yoshimoto, Arisa Ochi, Sayo Ueda, Kenji Nishimura, Eriko Shibata, Masanori Tamaki, Fumi Kishi, Seiji Kishi, Taichi Murakami, Kojiro Nagai, Toshio Doi

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Hideharu Abe
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Akiko Sakurai
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Hiroyuki Ono
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Sanae Hayashi
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Sakiya Yoshimoto
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Arisa Ochi
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Sayo Ueda
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Kenji Nishimura
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Eriko Shibata
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Masanori Tamaki
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Fumi Kishi
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Seiji Kishi
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Taichi Murakami
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Kojiro Nagai
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School
Toshio Doi
Department of Nephrology, Institute of Biomedical Sciences, Tokushima University Graduate School

Keywords: diabetic nephropathy, exosome, biomarker, WT1, PDSTF

JOURNAL FREE ACCESS

2018 Volume 65 Issue 3.4 Pages 208-215

DOI https://doi.org/10.2152/jmi.65.208

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Abstract

Diabetic nephropathy (DN) is the major cause of end‐stage renal failure and is associated with increased morbidity and mortality as compared to other causes of renal disease. Albuminuria is often the first clinical indicator of the presence of DN. However, albuminuria or proteinuria is a common symptom in patients with various renal disorders. Therefore, specific biomarkers for the diagnosis of DN are required. A primary hallmark of DN is the progressive damage and death of glomerular podocytes, resulting in the leaking of proteins into the urine. Urinary exosomes released by podocytes are microvesicles containing information of the originated cells. Podocyte‐derived signal transduction factors (PDSTFs) are good candidates to assess podocyte injuries. The profile of PDSTFs in urinary exosomes from patients with DN is different from that from patients with minimal change nehrotic syndrome. In addition, PDSTFs molecules in exosomes were derived from primary murine podocytes under high glucose conditions. Among PDSTFs in urinary exosomes, Wilms tumor 1 (WT1) levels reflected damage of diabetic glomeruli in the patients. Urinary exosomal WT1 can predict the decline in eGFR for the following several years. In conclusion, urinary exosomal WT1 is a useful biomarker to improve risk stratification in patients with DN. J. Med. Invest. 65:208‐215, August, 2018

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