Blood kinetics of TNF receptors for predicting CKD progression

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08617
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Juntendo University
• Principal Investigator: Gohda Tomohito 順天堂大学, 医学部, 先任准教授 (20365604)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病性腎臓病 / 慢性腎臓病 / TNF / プログラヌリン / 炎症

Outline of Final Research Achievements

1. The pattern of fractional excretion TNFRs showed that an increase in serum TNFRs might result from their increased systemic production, including in the kidney, rather than being a simple reflection of GFR decline.
2. The elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia.
3. PGRN deficiency was associated with both exacerbated renal inflammation and decreased systemic inflammation, including that in the adipose tissue of mice with high fat diet-induced obesity.

Free Research Field

腎臓病

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病の進展抑制には腎機能低下をきたしやすい患者を早期発見して治療することは極めて重要である。血中TNF受容体濃度の測定は、糖尿病合併の有無にかかわらず、CKD患者の予後予測に有用なことを明らかにした点で臨床的に意義がある。また、血中TNF受容体濃度の上昇機序のみならず、TNF-TNF受容体経路を介した炎症機序にプラグラヌリンが関与していることを明らかにした点でも重要な知見である。