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

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 & 5 others Liang Yin Ke, Chu Huang Chen, Teruki Yoshimura, Toshiaki Miura, Etsuro Ito

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere000661
JournalBMJ Open Diabetes Research and Care
Volume7
Issue number1
DOIs
Publication statusPublished - 2019 May 1

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Adiponectin
Diabetic Nephropathies
Chronic Renal Insufficiency
Diabetes Mellitus
Creatinine
Molecular Weight
Urine
Albuminuria
Glomerular Filtration Rate
Research Design
Enzyme-Linked Immunosorbent Assay

Keywords

  • adiponectin
  • chronic kidney disease
  • diabetes mellitus
  • non-invasive test
  • ultrasensitive ELISA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy. / Yamakado, Shinnosuke; Cho, Hiroki; Inada, Mikio; Morikawa, Mika; Jiang, Yong Huang; Saito, Kenji; Nakaishi, Kazunari; Watabe, Satoshi; Takagi, Hitomi; Kaneda, Mugiho; Nakatsuma, Akira; Ninomiya, Masaki; Imachi, Hitomi; Arai, Takeshi; Yoshimoto, Takuo; Murao, Koji; Chang, Jyun Hao; Chen, Shih Min; Shih, Yi Chen; Zeng, Min Jing; Ke, Liang Yin; Chen, Chu Huang; Yoshimura, Teruki; Miura, Toshiaki; Ito, Etsuro.

In: BMJ Open Diabetes Research and Care, Vol. 7, No. 1, e000661, 01.05.2019.

Research output: Contribution to journalArticle

Yamakado, S, Cho, H, Inada, M, Morikawa, M, Jiang, YH, Saito, K, Nakaishi, K, Watabe, S, Takagi, H, Kaneda, M, Nakatsuma, A, Ninomiya, M, Imachi, H, Arai, T, Yoshimoto, T, Murao, K, Chang, JH, Chen, SM, Shih, YC, Zeng, MJ, Ke, LY, Chen, CH, Yoshimura, T, Miura, T & Ito, E 2019, 'Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy', BMJ Open Diabetes Research and Care, vol. 7, no. 1, e000661. https://doi.org/10.1136/bmjdrc-2019-000661
Yamakado, Shinnosuke ; Cho, Hiroki ; Inada, Mikio ; Morikawa, Mika ; Jiang, Yong Huang ; Saito, Kenji ; Nakaishi, Kazunari ; Watabe, Satoshi ; Takagi, Hitomi ; Kaneda, Mugiho ; Nakatsuma, Akira ; Ninomiya, Masaki ; Imachi, Hitomi ; Arai, Takeshi ; Yoshimoto, Takuo ; Murao, Koji ; Chang, Jyun Hao ; Chen, Shih Min ; Shih, Yi Chen ; Zeng, Min Jing ; Ke, Liang Yin ; Chen, Chu Huang ; Yoshimura, Teruki ; Miura, Toshiaki ; Ito, Etsuro. / Urinary adiponectin as a new diagnostic index for chronic kidney disease due to diabetic nephropathy. In: BMJ Open Diabetes Research and Care. 2019 ; Vol. 7, No. 1.
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AU - Yamakado, Shinnosuke

AU - Cho, Hiroki

AU - Inada, Mikio

AU - Morikawa, Mika

AU - Jiang, Yong Huang

AU - Saito, Kenji

AU - Nakaishi, Kazunari

AU - Watabe, Satoshi

AU - Takagi, Hitomi

AU - Kaneda, Mugiho

AU - Nakatsuma, Akira

AU - Ninomiya, Masaki

AU - Imachi, Hitomi

AU - Arai, Takeshi

AU - Yoshimoto, Takuo

AU - Murao, Koji

AU - Chang, Jyun Hao

AU - Chen, Shih Min

AU - Shih, Yi Chen

AU - Zeng, Min Jing

AU - Ke, Liang Yin

AU - Chen, Chu Huang

AU - Yoshimura, Teruki

AU - Miura, Toshiaki

AU - Ito, Etsuro

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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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