Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.55

July 16, 2018

Source: Okayama University (JAPAN), Public Relations and Information Strategy
For immediate release: 16 July 2018
Okayama University research: Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis

(Okayama, 16 July) Researchers at Okayama University report in the journal Diabetes Care their findings on measurements of ion concentration in solutions for clinical and environmental research. The results are expected to improve prognosis of diabetic kidney disease.

One of the complications of diabetes is diabetic kidney disease (DKD), a condition in which the kidneys do not filter blood correctly and, eventually, fail - DKD is one of the most common causes of kidney failure and affects around 40% of patients with diabetes. DKD is normally diagnosed by checking for proteins, in particular albumin, that leak from the blood into the urine as a consequence of the malfunctioning filtering; these proteins are used as biomarkers to monitor the progression of DKD and predict the renal prognosis at the early stages of disease. However, new biomarkers that could help to identify the onset of DKD earlier and to predict the renal prognosis more accurately would be very beneficial to help patients with a rapid deterioration of renal function.

Recently it has emerged that glycans - complex molecules made of interlocking sugar molecules - and their enzymatic modification (glycosylation) have a role in diabetes and in the progression of DKD. Because of their complicated structure, glycans are technically difficult to quantify in urine samples, and few studies exist about the role of glycosylation in DKD. However, a method previously introduced by Professor Jun Wada, Dr.Koki Mise and colleagues at the University of Okayama in Japan, authors also of the present study, enables high-throughput quantification of the binding of glycan to 45 different proteins, opening up the investigation of the association between the glycosylation profile in the urine and the renal prognosis in patients with diabetes.

The study that the authors report in the newly published paper started in 2012 and involved 688 patients with type 2 diabetes, who were monitored over a period of 4 years, and 134 control patients with neither diabetes nor DKD. The results suggest that levels of glycans are significantly associated with the evolution of renal function, and that changes in the glycosylation of a particular protein occur in the early stages of DKD, before other detectable signs of deterioration of renal function develop. Because the indexes for glycans are associated with the renal prognosis independent of other indicators commonly used, adding the combined glycan index to other indicators of the progression of disease can significantly improve the prediction of the renal outcome. The results of the current study are also of fundamental interest, as they provide insight in how glycosylation changes in DKD.

Diabetic kidney disease

Diabetic kidney disease is a complication of diabetes (both type 1 and type 2), arising because the high blood glucose can damage the blood vessels in the kidneys. As a result, the kidneys become unable to filter blood in a normal way, wastes accumulate in the body and proteins such as albumin are found in the urine. The presence of albumin in urine is a common way of diagnosing DKD, as normally the disease causes no clear symptoms before reaching the advanced stages.

Glycans and glycosylation
Glycans are complex molecules consisting of a large number of sugar molecules linked in a particular way; they can attach to a variety of biological molecules, in particular proteins, through an enzymatic process called glycosylation.

Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Sanae Teshigawara, Atsuhito Tone, Haruhito A. Uchida, Jun Eguchi, Atsuko Nakatsuka, Daisuke Ogawa, Michihiro Yoshida, Masao Yamada, Kenichi Shikata and Jun Wada. Identification of novel urinary biomarkers for predicting the renal prognosis in patients with type 2 diabetes by glycan profiling in a multicenter prospective cohort study: U-CARE Study 1. Diabetes Care, 2018 Jun ; dc180030.
DOI: https://doi.org/10.2337/dc18-0030

Reference (Okayama Univ. e-Bulletin): Professor Wada’s team
e-Bulletin Vol.2:LInflammation and diabetic nephropathy
OU-MRU Vol.18:Therapeutic protein targets liver disease
OU-MRU Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
OU-MRU Vol.24:Sticky molecules to tackle obesity and diabetes

Correspondence to
Professor Jun Wada, M.D., Ph.D.
Department of Medicine and Clinical Science,
Okayama University Graduate School of Medicine,
Dentistry, and Pharmaceutical Sciences, 2-5-1,
Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
E-mail: junwada(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Public Relations and Information Strategy
E-mail: www-adm (a) adm.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
Website: //www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin: //www.okayama-u.ac.jp/user/kouhou/ebulletin/
About Okayama University (You Tube): https://www.youtube.com/watch?v=iDL1coqPRYI
Okayama University Image Movie (You Tube): https://www.youtube.com/watch?v=KU3hOIXS5kk

Okayama University Medical Research Updates (OU-MRU)
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research