The clinical application of a novel biomarker and therapeutic strategy in diabetic kidney disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23994
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0904:Internal medicine of the bio-information integration and related fields
• Research Institution: Tohoku University
• Principal Investigator: KIKUCHI Koichi 東北大学, 東北メディカル・メガバンク機構, 助教 (10845259)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 糖尿病性腎臓病 / 腸内細菌叢 / フェニル硫酸 / チロシンフェノールリアーゼ / 末期腎不全 / バイオマーカー

Outline of Final Research Achievements

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal diseases (ESRD) in Japan, and it is very important to prevent from onset or progression of DKD.
In previous study (Kikuchi et al Nat. Med. 2019), we identified phenyl sulfate (PS) as a novel biomarker of DKD. PS is a metabolite of phenol which produced from tyrosine by tyrosine-phenol lyase (TPL). PS administration in several types of diabetic nephropathy model significantly induced albuminuria and podocyte damage, suggesting that PS may be one of the causes of albuminuria in db/db mice.In this study, we clarify that a production of PS is increased in diabetic condition according to change gut microbiota. This implied microbiota may be a therapeutic target in DKD. Next, we identified compounds which decreasing plasma PS concentration by pharmacological screening because we clarify the reduction of PS have reno-protective effect.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病は末期腎不全に至る最多原疾患であり、腎不全に至ると透析治療を余儀なくされる。末期腎不全は患者のQOLを著しく低下させるだけでなく、透析治療には患者一人あたり年間約500万円の医療費がかかっており医療経済的にも末期腎不全患者数を減らすことは極めて重要である。本研究は腸内細菌叢に着目し糖尿病性腎臓病の新たな発症予測マーカーや治療法の可能性を示したものであり、学術的・社会的意義は大である。