Article Text
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.
- adiponectin
- chronic kidney disease
- diabetes mellitus
- non-invasive test
- ultrasensitive ELISA
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Footnotes
SY and HC contributed equally.
Contributors KN, SW, KM, and EI designed the study. SY, HC, MI, MM, YHJ, KS, HT, MK, AN, MN, HI, TA, TY, KM, JHC, SMC, YCS, MJZ, LYK, and CHC collected and analyzed the data. TY, TM, and EI interpreted and analyzed the data. SY, HC, KM, TY, TM and EI wrote the manuscript. EI is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This work was supported by a Grant for the Development of Systems and Technology for Advanced Measurement and Analysis from JST, a grant for the Regional Innovation Strategy Support Program from MEXT, Waseda University Grants for Specific Research Projects (2017A-015, 2019C-123) and the Precise Measurement Technology Promotion Foundation to EI.
Competing interests MM, YHJ, KS, KN, and SW are employees of TAUNS Laboratories.
Patient consent for publication Not required.
Ethics approval The study was approved by the ethics committees at Waseda University, Tokushima Bunri University, and Kagawa University.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.