Transcriptome analysis of kidney biopsied tissues of diabetic kidney disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08741
• 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: National Hospital Organization Chiba-East-Hospital
• Principal Investigator: Imasawa Toshiyuki 独立行政法人国立病院機構(千葉東病院臨床研究部), 腎センター, 腎センター長 (80348276)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 糖尿病性腎臓病 / 結節病変 / トランスクリプトーム解析

Outline of Final Research Achievements

It is known that diabetic kidney disease (DKD) patients with nodular lesions (NL) have a poor prognosis (rapid decline in eGFR), but some patients with NL also have a slow decline in eGFR. The purpose of this study was to explore factors associated with this difference in prognosis in order to identify renal protective factors. To this end, in this study, we performed transcriptome analysis on the remaining preserved renal biopsy specimens of patients with pathologically diagnosed DKD with NL after renal biopsy. In addition, bioinformatics analysis was performed to search for upstream factors in prognosis determination based on the results obtained.As a result, CDH1, CD24, and ESR1 have been selected as candidate of renoprotective factors. Furthermore, qRT-PCR and immunostaining of residual renal tissue from the same patients showed that ESR1 expression was enhanced in the good prognosis group. ESR1 may have a renoprotective effect on DKD with nodal involvement.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

糖尿病性腎臓病（DKD）において結節性病変（NL）を有する症例では予後が悪い（eGFR低下スピードが急速）であることが知られており、現在有効な治療法がない。しかし実臨床においては、NLを有する症例でもeGFR低下が緩やかな症例もあり、予後の良い症例と悪い症例の差を生み出している因子を探求することで、腎保護因子が見いだされれば、新たな治療法に繋がり、NLを有するDKDの予後を改善させることができる可能性がある。今回我々はNLを有するDKDにおいてESR1が腎予後を改善する可能性がある因子であることを初めて見出した意義は以上の点からも大きな意義があると考えられる。