Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy

Objective The chronic kidney disease (CKD) is widely diagnosed on the basis of albuminuria and the glomerular filtration rate. A more precise diagnosis of CKD, however, requires the assessment of other factors. Urinary adiponectin recently attracted attention for CKD assessment, but evaluation is di...

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Main Authors: Shinnosuke Yamakado, Hiroki Cho, Mikio Inada, Mika Morikawa, Yong-Huang Jiang, Kenji Saito, Kazunari Nakaishi, Satoshi Watabe, Hitomi Takagi, Mugiho Kaneda, Akira Nakatsuma, Masaki Ninomiya, Hitomi Imachi, Takeshi Arai, Takuo Yoshimoto, Koji Murao, Jyun-Hao Chang, Shih-Min Chen, Yi-Chen Shih, Min-Jing Zeng, Liang-Yin Ke, Chu-Huang Chen, Teruki Yoshimura, Toshiaki Miura, Etsuro Ito
Format: Article
Language:English
Published: BMJ Publishing Group 2019-05-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/7/1/e000661.full
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author Shinnosuke Yamakado
Hiroki Cho
Mikio Inada
Mika Morikawa
Yong-Huang Jiang
Kenji Saito
Kazunari Nakaishi
Satoshi Watabe
Hitomi Takagi
Mugiho Kaneda
Akira Nakatsuma
Masaki Ninomiya
Hitomi Imachi
Takeshi Arai
Takuo Yoshimoto
Koji Murao
Jyun-Hao Chang
Shih-Min Chen
Yi-Chen Shih
Min-Jing Zeng
Liang-Yin Ke
Chu-Huang Chen
Teruki Yoshimura
Toshiaki Miura
Etsuro Ito
author_facet Shinnosuke Yamakado
Hiroki Cho
Mikio Inada
Mika Morikawa
Yong-Huang Jiang
Kenji Saito
Kazunari Nakaishi
Satoshi Watabe
Hitomi Takagi
Mugiho Kaneda
Akira Nakatsuma
Masaki Ninomiya
Hitomi Imachi
Takeshi Arai
Takuo Yoshimoto
Koji Murao
Jyun-Hao Chang
Shih-Min Chen
Yi-Chen Shih
Min-Jing Zeng
Liang-Yin Ke
Chu-Huang Chen
Teruki Yoshimura
Toshiaki Miura
Etsuro Ito
author_sort Shinnosuke Yamakado
collection DOAJ
description Objective The chronic kidney disease (CKD) is widely diagnosed on the basis of albuminuria and the glomerular filtration rate. A more precise diagnosis of CKD, however, requires the assessment of other factors. Urinary adiponectin recently attracted attention for CKD assessment, but evaluation is difficult due to the very low concentration of urinary adiponectin in normal subjects.Research design and methods We developed an ultrasensitive ELISA coupled with thionicotinamide-adenine dinucleotide cycling to detect trace amounts of proteins, which allows us to measure urinary adiponectin at the subattomole level. We measured urinary adiponectin levels in 59 patients with diabetes mellitus (DM) and 24 subjects without DM (normal) to test our hypothesis that urinary adiponectin levels increase with progression of CKD due to DM.Results The urinary adiponectin levels were 14.88±3.16 (ng/mg creatinine, mean±SEM) for patients with DM, and 3.06±0.33 (ng/mg creatinine) for normal subjects. The threshold between them was 4.0 ng/mg creatinine. The urinary adiponectin levels increased with an increase in the CKD risk. Furthermore, urinary adiponectin mainly formed a medium-molecular weight multimer (a hexamer) in patients with DM, whereas it formed only a low-molecular weight multimer (a trimer) in normal subjects. That is, the increase in urinary adiponectin in patients with DM led to the emergence of a medium-molecular weight form in urine.Conclusions Our new assay showed that urinary adiponectin could be a new diagnostic index for CKD. This assay is a non-invasive test using only urine, thus reducing the patient burden.
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spelling doaj-art-b100368e04c046eea405aea7cc3cf2262025-08-20T02:49:02ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972019-05-017110.1136/bmjdrc-2019-000661Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathyShinnosuke Yamakado0Hiroki Cho1Mikio Inada2Mika Morikawa3Yong-Huang Jiang4Kenji Saito5Kazunari Nakaishi6Satoshi Watabe7Hitomi Takagi8Mugiho Kaneda9Akira Nakatsuma10Masaki Ninomiya11Hitomi Imachi12Takeshi Arai13Takuo Yoshimoto14Koji Murao15Jyun-Hao Chang16Shih-Min Chen17Yi-Chen Shih18Min-Jing Zeng19Liang-Yin Ke20Chu-Huang Chen21Teruki Yoshimura22Toshiaki Miura23Etsuro Ito24Department of Biology, Waseda University, Shinjuku, Tokyo, JapanDepartment of Biology, Waseda University, Shinjuku, Tokyo, JapanDepartment of Biology, Waseda University, Shinjuku, Tokyo, JapanR&D Headquarters, TAUNS Laboratories, Izunokuni, Shizuoka, JapanR&D Headquarters, TAUNS Laboratories, Izunokuni, Shizuoka, Japan1 Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanR&D Headquarters, TAUNS Laboratories, Izunokuni, Shizuoka, JapanR&D Headquarters, TAUNS Laboratories, Izunokuni, Shizuoka, JapanKagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, JapanKagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, JapanKagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, JapanKagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, JapanFaculty of Medicine, Kagawa University, Miki, Kagawa, JapanFaculty of Medicine, Kagawa University, Miki, Kagawa, JapanFaculty of Medicine, Kagawa University, Miki, Kagawa, JapanFaculty of Medicine, Kagawa University, Miki, Kagawa, JapanLipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanLipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanLipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanLipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, TaiwanLipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan5 Vascular and Medicinal Research, Texas Heart Institute, Houston, Texas, USAFaculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, JapanGraduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, JapanDepartment of Biology, Waseda University, Shinjuku, Tokyo, JapanObjective The chronic kidney disease (CKD) is widely diagnosed on the basis of albuminuria and the glomerular filtration rate. A more precise diagnosis of CKD, however, requires the assessment of other factors. Urinary adiponectin recently attracted attention for CKD assessment, but evaluation is difficult due to the very low concentration of urinary adiponectin in normal subjects.Research design and methods We developed an ultrasensitive ELISA coupled with thionicotinamide-adenine dinucleotide cycling to detect trace amounts of proteins, which allows us to measure urinary adiponectin at the subattomole level. We measured urinary adiponectin levels in 59 patients with diabetes mellitus (DM) and 24 subjects without DM (normal) to test our hypothesis that urinary adiponectin levels increase with progression of CKD due to DM.Results The urinary adiponectin levels were 14.88±3.16 (ng/mg creatinine, mean±SEM) for patients with DM, and 3.06±0.33 (ng/mg creatinine) for normal subjects. The threshold between them was 4.0 ng/mg creatinine. The urinary adiponectin levels increased with an increase in the CKD risk. Furthermore, urinary adiponectin mainly formed a medium-molecular weight multimer (a hexamer) in patients with DM, whereas it formed only a low-molecular weight multimer (a trimer) in normal subjects. That is, the increase in urinary adiponectin in patients with DM led to the emergence of a medium-molecular weight form in urine.Conclusions Our new assay showed that urinary adiponectin could be a new diagnostic index for CKD. This assay is a non-invasive test using only urine, thus reducing the patient burden.https://drc.bmj.com/content/7/1/e000661.full
spellingShingle Shinnosuke Yamakado
Hiroki Cho
Mikio Inada
Mika Morikawa
Yong-Huang Jiang
Kenji Saito
Kazunari Nakaishi
Satoshi Watabe
Hitomi Takagi
Mugiho Kaneda
Akira Nakatsuma
Masaki Ninomiya
Hitomi Imachi
Takeshi Arai
Takuo Yoshimoto
Koji Murao
Jyun-Hao Chang
Shih-Min Chen
Yi-Chen Shih
Min-Jing Zeng
Liang-Yin Ke
Chu-Huang Chen
Teruki Yoshimura
Toshiaki Miura
Etsuro Ito
Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
BMJ Open Diabetes Research & Care
title Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
title_full Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
title_fullStr Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
title_full_unstemmed Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
title_short Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
title_sort urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy
url https://drc.bmj.com/content/7/1/e000661.full
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