The clinical application of a novel biomarker of DKD and the clarification of gut-microbiota axis in DKD

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16178
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tohoku University
• Principal Investigator: Kikuchi Koichi 東北大学, 大学病院, 助教 (10845259)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 糖尿病性腎臓病 / 尿毒素 / 腸腎連関 / フェニル硫酸 / UCARE study / 腸内細菌 / バイマーカー

Outline of Final Research Achievements

We focused on phenyl sulfate (PS) as a novel marker of diabetic kidney disease (DKD) and demonstrated its clinical utility in two diabetic cohorts.
First, in the UCARE cohort (Nat. Commun. 2019), where blood PS levels and albuminuria (ACR) exacerbation in DKD patients have been shown, multiple regression analysis showed that urinary PS and Cr corrected values significantly correlated with ACR, and in the group of patients in the microalbuminuria phase, urinary PS and Cr corrected values significantly correlated with ACR exacerbation after 2 years The urinary PS and Cr corrected values were significantly correlated with worsening of ACR at 2 years in patients with trace albuminuria. Next, the 2nd Joslin Kidney Study explored risk factors for the onset and progression of nephropathy in patients with type 2 diabetes. Comparing two groups, one with slow progression of nephropathy and the other with onset of renal failure, PS was significantly higher in the group with onset of renal failure.

Free Research Field

腎臓

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病（DKD）は末期腎不全に至る最も多い原疾患だが、アルブミン尿（ACR）やeGFRといった既存の指標だけでは、どの糖尿病患者がDKDを発症し腎不全に至るリスクが高いかを予測するには不十分である。我々はDKDの新規マーカーとして腸内細菌由来の尿毒素であるフェニル硫酸（PS）に着目し先行研究で血清PSは糖尿病患者のACR増悪を予測することを示しているが、今回の研究で尿中PSもACRの増悪を予測する因子であることを明らかにした。更に別の糖尿病患者コホートでの解析で血中PSが早期にeGFRが低下群で有意に高いことを示した。これらの成果はPSの新規DKDマーカーとしての有用性を示唆する。