Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis


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.

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.

4 types of promising glycans which could be useful prognostic indicators of DKD.
Our results suggest that higher levels of urinary excretion of Siaα2-6Gal/GalNac, Galβ1-4GlcNAc, and Galβ1-3GalNAc and lower levels of urinary excretion of GalNAcα1-3GalNAc could indicate poor renal prognosis in patients with type 2 diabetes.

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:Inflammation 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@okayama-u.ac.jp

Professor Jun Wada