KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 1995.04

  -

  1997.03

  慶應義塾大学医学部, 病理学教室, 慶應義塾大学医学部助手（病理学）

• 1997.04

  -

  2007.03

  慶應義塾大学医学部, 病理学教室, 慶應義塾大学助手（医学部病理学）

• 2007.04

  -

  2013.11

  慶應義塾大学医学部, 病理学教室, 慶應義塾大学助教（医学部病理学）

• 2013.12

  -

  Present

  慶應義塾大学医学部, 病理学教室, 慶應義塾大学専任講師（医学部病理学）

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1989.04

  -

  1995.03

  Keio University, School of Meicine

  University, Graduated

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士（医学）, Keio University, Dissertation, 2010.11

  Using immunofluorescent digital slide technology to quantify protein expression in archival paraffin-embedded tissue sections

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Human pathology

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Digital Pathology

• Renal Pathology

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Polyclonal immunoglobulin G deposits with distinctive appearance in the tubular basement membrane: a report of two cases

  Sakamaki Y., Hashiguchi A., Konishi K., Araki T., Tokuyama H.

  BMC Nephrology 26 ( 1 ) 591 2025.12

  Joint Work

  　View Summary

  Background: Tubulointerstitial diseases arise from various etiologies, including infections, medications, autoimmune conditions, and systemic disorders. The histological presentation of the tubulointerstitium in renal biopsies can vary considerably. When tubulointerstitial alterations are identified through light microscopy, additional evaluation with immunofluorescence and electron microscopy may assist in diagnosis. This report describes two slowly progressive atypical cases of tubulointerstitial disease. Renal biopsy in both cases revealed tubular atrophy and interstitial fibrosis with limited inflammatory cell infiltration, along with polyclonal linear immunoglobulin G (IgG) staining pattern along the thickened tubular basement membrane (TBM) and distinctive electron-dense deposits. Case 1: Case presentation: A 65-year-old Japanese man with a history of chronic obstructive pulmonary disease, benign prostatic hyperplasia, and hypertension presented with anorexia and malaise 1 week prior to admission. Blood tests demonstrated marked renal impairment. Renal biopsy findings included relatively preserved glomeruli, widespread tubular atrophy, and significant interstitial fibrosis. Immunofluorescence showed linear deposition of IgG as well as kappa and lambda light chains along the TBM. Complement components C3 was also positive, and C1q were weakly positive. IgG subclass staining revealed positivity for IgG1, IgG2, and IgG4. Electron microscopy revealed electron-dense deposits within the TBM and on the epithelial side of the TBM, exhibiting a mottled and speckled appearance. Case 2: A 52-year-old Japanese man who had undergone allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia developed mild proteinuria and renal dysfunction 7 years after transplant. Renal biopsy indicated thrombotic microangiopathy, with glomeruli showing diffuse mesangial expansion and focal mesangiolysis. There was also diffuse TBM thickening and interstitial fibrosis with scattered cellular infiltration. Immunofluorescence demonstrated linear staining of polyclonal IgG and both light chains along the TBM. C3 was also positive while C1q was negative. IgG subclass staining revealed positivity for IgG1 and IgG4. Electron microscopy again identified electron-dense deposits within the reticulated TBM. Conclusions: These two cases demonstrated linear IgG immunofluorescence and distinctive electron-dense deposits in the TBM characterized by a mottled and speckled pattern. Although the underlying pathophysiological mechanisms remain unclear, further research is necessary to elucidate the nature of this form of tubulointerstitial disease.

  • Access to Document (DOI)

• DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages

  Nishimura E.S., Hishikawa A., Nakamichi R., Akashio R., Chikuma S., Hashiguchi A., Yoshimoto N., Hama E.Y., Maruki T., Itoh W., Yamaguchi S., Yoshino J., Itoh H., Hayashi K.

  Nature Communications 16 ( 1 ) 3958 2025.12

  Joint Work

  　View Summary

  DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis reveals expansion of CD11c+ Ccr2+ macrophages in the kidney cortex, liver, and adipose tissues and Ly6C^hi monocytes in peripheral blood. DNA damage in PTECs is associated with hypomethylation of macrophage activation genes, including Gasdermin D, in peripheral blood cells, which is linked to reduced DNA methylation at KLF9-binding motifs. Macrophage depletion ameliorates metabolic abnormalities. These findings highlight the impact of kidney DNA damage on systemic metabolic homeostasis, revealing a kidney-blood-metabolism axis mediated by epigenetic changes in macrophages.

  • Access to Document (DOI)

• Human chorionic gonadotropin-positive cystic duct carcinoma with trophoblastic differentiation that exhibited an aggressive clinical course.

  Takemura Y., Matsuda K., Abe Y., Hashiguchi A., Kitago M., Nakano Y., Sonoda K., Kitagawa Y.

  BMJ case reports 18 ( 11 )  2025.11

  Joint Work

  • Access to Document (DOI)

• Quantification-based explainable artificial intelligence for deep learning decisions: clustering and visualization of quantitative morphometric features in hepatocellular carcinoma discrimination.

  Takagi G., Takeyama S., Abe T., Hashiguchi A., Sakamoto M., Suzuki K., Yamaguchi M.

  Journal of medical imaging (Bellingham, Wash.) 12 ( 6 ) 061407 2025.11

  Joint Work,  ISSN  2329-4302

  　View Summary

  Purpose: Deep learning (DL) is rapidly advancing in computational pathology, offering high diagnostic accuracy but often functioning as a “black box” with limited interpretability. This lack of transparency hinders its clinical adoption, emphasizing the need for quantitative explainable artificial intelligence (QXAI) methods. We propose a QXAI approach to objectively and quantitatively elucidate the reasoning behind DL model decisions in hepatocellular carcinoma (HCC) pathological image analysis. Approach: The proposed method utilizes clustering in the latent space of embeddings generated by a DL model to identify regions that contribute to the model’s discrimination. Each cluster is then quantitatively characterized by morphometric features obtained through nuclear segmentation using HoverNet and key feature selection with LightGBM. Statistical analysis is performed to assess the importance of selected features, ensuring an interpretable relationship between morphological characteristics and classification outcomes. This approach enables the quantitative interpretation of which regions and features are critical for the model’s decision-making, without sacrificing accuracy. Results: Experiments on pathology images of hematoxylin-and-eosin-stained HCC tissue sections showed that the proposed method effectively identified key discriminatory regions and features, such as nuclear size, chromatin density, and shape irregularity. The clustering-based analysis provided structured insights into morphological patterns influencing classification, with explanations evaluated as clinically relevant and interpretable by a pathologist. Conclusions: Our QXAI framework enhances the interpretability of DL-based pathology analysis by linking morphological features to classification decisions. This fosters trust in DL models and facilitates their clinical integration.

  • Access to Document (DOI)

• Association Between Urinary Fractional Excretion of Potassium and Proteinuria Remission in Adult Nephrotic Syndrome.

  Yoshida R., Nakayama T., Mitsuno R., Komatsu M., Oshima Y., Iwabuchi S., Itoh T., Matsumoto D., Kusahana E., Hoshi K., Nakamura K., Fujii K., Hara Y., Kawaguchi T., Futatsugi K., Yamaji Y., Tokuyama H., Murakami M., Takimoto C., Matsuda H., Ando T., Hashiguchi A., Kaneko Y., Azegami T., Hayashi K.

  Kidney360  2025.10

  Joint Work

  • Access to Document (DOI)

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Papers, etc., Registered in KOARA 【 Display / hide 】

Papers, etc., Registered in KOARA 【 Display / hide 】

• The results of renal biopsies performed within the past thirty five years at Keio University Hospital, with an analysis in detail of the cases with membranous nephropathy.

  Hashiguchi, Akinori

  Journal of the Keio Medical Society (慶應医学会)  82 ( 3 ) 143 - 155 2005.09

  ISSN  03685179

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Erratum: DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation (Cell Reports (2023) 42(4), (S2211124723003133), (10.1016/j.celrep.2023.112302))

  Nakamichi R., Hishikawa A., Chikuma S., Yoshimura A., Sasaki T., Hashiguchi A., Abe T., Tokuhara T., Yoshimoto N., Nishimura E.S., Hama E.Y., Azegami T., Nakayama T., Hayashi K., Itoh H.

  Cell Reports (Cell Reports)  42 ( 5 )  2023.05

  Joint Work

  　View Summary

  (Cell Reports 42, 112302; April 25, 2023) In the originally published version of this article, Figure 4 was accidentally constructed with a duplicate of panel (D) in place of the intended panel (E). The figure has been corrected online. The authors regret this error. [Formula presented] [Formula presented]

  • Access to Document (DOI)

• Minimal Change Disease Associated With Durvalumab

  Toda M.G., Fujii K., Kato A., Yoshifuji A., Komatsu M., Amino Y., Kitazono S., Hashiguchi A., Ryuzaki M.

  Kidney International Reports (Kidney International Reports)  6 ( 10 ) 2733 - 2734 2021.10

  Article, review, commentary, editorial, etc. (scientific journal), Joint Work,  ISSN  24680249

  • Access to Document (DOI)

• IgA腎症のOxford分類と日本分類(組織学的重症度分類)の腎機能予後予測に関する比較

  城 謙輔, 中里 毅, 橋口 明典, 清水 章, 久野 敏, 片渕 律子, 川村 哲也

  日本腎臓学会誌 ((一社)日本腎臓学会)  61 ( 3 ) 394 - 394 2019.05

  Other, Joint Work,  ISSN  0385-2385

• IgA腎症の生検時の臨床データと病理所見の関連性

  鎌野 千佐子, 清水 章, 城 謙輔, 橋口 明典, 久野 敏, 片渕 律子, 川村 哲也

  日本腎臓学会誌 ((一社)日本腎臓学会)  61 ( 3 ) 395 - 395 2019.05

  Other, Joint Work,  ISSN  0385-2385

• 前立腺癌の腫瘍局在が診断・治療・予後に及ぼす影響

  松本 一宏, 高松 公晴, 武田 利和, 小坂 威雄, 田中 伸之, 森田 伸也, 水野 隆一, 篠島 利明, 菊地 栄次, 浅沼 宏, 橋口 明典, 陣崎 雅弘, 大家 基嗣

  日本泌尿器科学会総会 ((一社)日本泌尿器科学会総会事務局)  107回   PP1 - 075 2019.04

  Other, Joint Work

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Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• C3染色性が減弱した膜性腎症におけるCD35発現の検討

  小口 英世, 橋口 明典, 高上 紀之, 三上 哲夫, 栃木 直文, 酒井 謙

  日本腎臓学会誌, 

  2025.09

  , 

  (一社)日本腎臓学会

• Multiple Instance Learningを用いたIgA腎症病理画像の重症度分類と識別要因解析

  高木 弦, 武山 彩織, 阿部 時也, 橋口 明典, 山口 雅浩

  日本医用画像工学会大会予稿集, 

  2025.08

  , 

  (一社)日本医用画像工学会

  　View Summary

  IgA腎症は慢性糸球体腎炎の中で最も頻度が高く,日本では指定難病に分類される.その臨床・病理組織像は多彩で,病理組織学的評価による疾患の層別化が診療にあたり重要となる.本研究では,腎生検由来の病理画像から病理医により抽出された糸球体画像から臨床的重症度を予測する手法を提案する.本手法では,Multiple Instance Learning(MIL)とAttentionを組み合わせた深層学習モデルにより,症例ごとに異なる数の糸球体情報を統合しつつ,効果的な学習を可能としている.加えて,Attention重みの可視化により,モデルの判断根拠となる糸球体領域を同定し,説明可能性の観点からも有用性を検証した.(著者抄録)

• Multiple Instance Learningを用いたIgA腎症病理画像の重症度分類と識別要因解析

  高木 弦, 武山 彩織, 阿部 時也, 橋口 明典, 山口 雅浩

  日本医用画像工学会大会予稿集, 

  2025.08

  , 

  (一社)日本医用画像工学会

• Focal global glomerulosclerosis経過中にネフローゼ症候群を発症したMinimal change diseaseの1例

  吉見 公志, 大島 洋一, 圓谷 泰章, 加藤 亜唯, 橋口 明典, 小松 素明

  日本内科学会関東地方会, 

  2025.07

  , 

  日本内科学会-関東地方会

• 【ヘマトネフロロジー】各疾患と腎障害の相互の病態関連と腎障害に対する治療 原発性マクログロブリン血症の病理と鑑別疾患

  橋口 明典

  腎と透析, 

  2025.07

  , 

  (株)東京医学社

  　View Summary

  ＜文献概要＞はじめに 原発性マクログロブリン血症(Waldenstroemマクログロブリン血症:WM)は,1944年,Jan Goesta Waldenstroemによって,口・鼻腔出血,リンパ節腫大,貧血,血小板減少,赤沈更新,高血漿粘度,骨放射線画像正常,リンパ球優位の骨髄を有した2名の患者について記述されたのが,最初の報告である。現在では,リンパ形質細胞性リンパ腫のサブセットとして,骨髄のリンパ形質細胞性リンパ腫(lymphoplasmacytic lymphoma:LPL)と血中単クローン性免疫グロブリンM(IgM)によって定義される。本稿では,WM血液腫瘍としての鑑別診断と,本疾患によって起こる腎疾患の形態分類について概説したい。

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• GENERAL PATHOLOGY

  2025

• DISEASES OF ORGAN SYSTEMS

  2025

• GENERAL PATHOLOGY

  2024

• DISEASES OF ORGAN SYSTEMS

  2024

• GENERAL PATHOLOGY

  2023

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 病理学各論（講義）

  Keio University

  2017.04

  -

  2018.03

  , 

  Lecture

• 臨床実習（病理診断部）

  Keio University

  2017.04

  -

  2018.03

  , 

  Laboratory work/practical work/exercise

• 病理学各論（実習）

  Keio University

  2017.04

  -

  2018.03

  , 

  Laboratory work/practical work/exercise

• 病理学総論（実習）

  Keio University

  2017.04

  -

  2018.03

  , 

  Laboratory work/practical work/exercise

• 病理学各論（講義）

  Keio University

  2016.04

  -

  2017.03

  , 

  Lecture

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• The Japanese Society of Pathology

  　

• Japanese Society of Nephrology

  　

• The Japanese Society of Digital Pathology