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 】

• Biopsy-proven kidney-limited thrombotic microangiopathy associated with bevacizumab and pegylated liposomal doxorubicin: a case with a biphasic clinical course

  Chigusa N., Azegami T., Nakayama T., Yoshimoto N., Hishikawa A., Hagiwara A., Hashiguchi A., Hayashi K.

  Cen Case Reports 15 ( 5 )  2026.10

  Joint Work

  　View Summary

  Drug-induced thrombotic microangiopathy (TMA) is an important cause of kidney injury in patients receiving anticancer therapy, although kidney-limited forms without systemic manifestations are often difficult to recognize. Pegylated liposomal doxorubicin (PLD)-associated TMA remains under-recognized, particularly in patients receiving concomitant vascular endothelial growth factor (VEGF) inhibitors. We report a case of biopsy-proven kidney-limited TMA associated with bevacizumab and PLD in a 52-year-old woman with metastatic ovarian serous adenocarcinoma, characterized by a biphasic clinical course. She developed progressive kidney dysfunction and proteinuria during treatment with bevacizumab followed by PLD. Despite discontinuation of bevacizumab, kidney dysfunction persisted. Kidney biopsy demonstrated findings consistent with TMA, including mesangiolysis, glomerular basement membrane duplication, and focal PAS-positive pseudothrombi suggestive of VEGF inhibitor–associated endothelial injury. Electron microscopy further revealed endothelial detachment, accompanied by a substance containing liposome-like particles, suggestive of the characteristic ultrastructural findings previously reported in PLD-associated TMA. The patient had no evidence of microangiopathic hemolytic anemia or thrombocytopenia, and no alternative cause of TMA was identified. Following discontinuation of PLD, kidney function improved markedly with complete resolution of proteinuria. This case highlights the importance of kidney biopsy and careful clinicopathological correlation in diagnosing drug-induced kidney-limited TMA.

  • Access to Document (DOI)

• Long-Term Clinical Course of COL4A1-Associated Nephropathy and Assessment of α1 Chain of Type IV Collagen Expression in Kidney Biopsy Specimens: A Case Report

  Yoshida R., Hashiguchi A., Nakayama T., Nakamura T., Miya F., Kosaki K., Azegami T., Hayashi K.

  American Journal of Kidney Diseases 88 ( 4 ) 631 - 635 2026.10

  Joint Work,  ISSN  02726386

  　View Summary

  COL4A1 variants cause a spectrum of systemic disorders encompassed by Gould syndrome. While kidney involvement is recognized, its long-term progression and detailed kidney pathology remain uncharacterized. We present a 39-year-old man with a heterozygous p.G1239R COL4A1 variant, persistent microscopic hematuria, and a progressive estimated glomerular filtration rate decline of −1.2 mL/min/1.73 m² per year over a 10-year follow-up. Light microscopy showed only focal global glomerulosclerosis and mild tubular dilatation. Immunofluorescence for the α1 chain of type IV collagen (α1[IV]) revealed reduced signal intensity in the tubular basement membrane (TBM). Electron microscopy demonstrated focal thinning of the glomerular basement membrane (GBM) and heterogeneous abnormalities, including thinning, focal thickening, reticulation, and lamellation, of the TBM. Immunoelectron microscopy using FluoroNanogold showed decreased density of gold particles in the TBM, correlating with the fluorescence intensity. This report analyzes COL4A1 expression using correlative light and electron microscopy (CLEM), and describes the long-term kidney function decline. In patients with hematuria and a thin GBM, in addition to Alport syndrome, COL4A1 -associated nephropathy should also be considered. Recognizing this entity is essential for accurate systemic risk assessment and genetic counseling. Semi-quantitative assessment of COL4A1 expression in biopsy specimens using CLEM may be a key diagnostic tool for patients with heterozygous COL4A1 variants.

  • Access to Document (DOI)

• Kidney-limited thrombotic microangiopathy caused by relative hypertension in a hemodynamically vulnerable kidney allograft, mimicking malignant hypertension

  Sugihara S., Azegami T., Morita S., Hashiguchi A., Hayashi K.

  Cen Case Reports 15 ( 3 )  2026.06

  Joint Work

  　View Summary

  Malignant hypertension is traditionally defined as severe systemic blood pressure elevation accompanied by end-organ damage. In kidney transplant recipients, however, kidney allografts may be particularly vulnerable to hypertensive injury even at lower blood pressure levels, owing to impaired autoregulation associated with denervation and calcineurin inhibitor exposure. We report a 52-year-old kidney transplant recipient presenting with severe kidney injury (serum creatinine, 4.90 mg/dL) 16 months after transplantation. Although systemic blood pressure remained within the range of 140–170/90–105 mmHg—below the classical threshold of malignant hypertension—an allograft biopsy revealed the lesions suggestive of thrombotic microangiopathy (TMA), including mesangiolysis and edematous intimal thickening of the arteries. After exclusion of antibody-mediated rejection, calcineurin inhibitor toxicity, and primary TMAs, the patient was diagnosed with kidney-limited TMA attributable to relative hypertension producing a malignant hypertension-like phenotype in the setting of graft-specific vulnerability. Given the presumed contribution of the renin-angiotensin system (RAS)-mediated vascular injury, an angiotensin II receptor blocker was initiated despite severe kidney dysfunction, resulting in marked improvement in kidney function and proteinuria. This case illustrates that kidney allografts may develop a malignant hypertension-like pathophysiology with kidney-limited TMA at blood pressure levels below the classical malignant range. Awareness of this discrepancy may help clinicians recognize atypical hypertensive injury in transplant recipients, and early RAS blockade may be considered as a potential strategy to preserve allograft function, even in the setting of severe kidney injury.

  • Access to Document (DOI)

• Endothelial DNA Damage Orchestrates Cardio-Kidney-Metabolic Dysfunction Through Endothelin-1 Signaling

  Ito W., Nakamichi R., Hishikawa A., Yoshimoto N., Nishimura E.S., Hama E.Y., Maruki T., Iwabuchi S., Yoshida R., Toda M., Kosugi S., Yamaguchi S., Kanda T., Hashiguchi A., Itoh H., Hayashi K.

  Arteriosclerosis Thrombosis and Vascular Biology 46 ( 6 ) e324564 2026.06

  Joint Work,  ISSN  10795642

  　View Summary

  BACKGROUND: – Cardiovascular diseases increase with aging and are closely linked to metabolic dysfunction and kidney disease through the cardiovascular-kidney-metabolic axis, but the underlying molecular mechanisms remain unclear. Accumulating evidence suggests that vascular endothelial cells (ECs) are particularly vulnerable to aging stressors, such as DNA damage. We investigated whether EC DNA damage drives cardiovascular-kidney-metabolic dysfunction. METHODS: – We generated mice with EC-specific DNA double-strand breaks using an endonuclease I-PpoI and subjected them to a high-fat diet (HFD). This approach allowed us to investigate the impact of EC-specific DNA damage on cardiovascular, metabolic, and renal systems. Furthermore, we analyzed the correlation between EC DNA damage markers (γH2AX [phosphorylated histone H2AX]) and clinical parameters in human kidney biopsy samples. RESULTS: – High-fat diet-fed endonuclease I-PpoI mice rapidly developed hypertension, dyslipidemia (low high-density lipoprotein cholesterol), hepatic steatosis, and visceral fat accumulation. Mechanistically, high-fat diet feeding compromised DNA repair capacity by suppressing ATM (ataxia-telangiectasia mutated) expression in the aorta. Consequently, DNA damage in aortic ECs triggered ET-1 (endothelin-1) secretion. This induced hepatic hypoxia and ETAR (endothelin type A receptor) activation, which promoted lipid metabolic reprogramming via ACSS2 (acetyl-CoA synthetase 2) upregulation. In addition, renal aging was accelerated. The selective ETAR antagonist atrasentan normalized blood pressure, reversed hepatic steatosis, restored high-density lipoprotein cholesterol, reduced visceral fat, and attenuated renal aging. In humans, EC DNA damage correlated negatively with estimated glomerular filtration rate and high-density lipoprotein cholesterol and positively with hepatic steatosis indices and renal cortical ETAR expression. CONCLUSIONS: – Endothelial DNA damage is a pivotal driver of cardiovascular-kidney-metabolic dysfunction through the ET-1-ETAR-ACSS2 signaling cascade. ETAR blockade offers a mechanism-based therapeutic strategy for age-related cardiovascular, renal, and metabolic diseases.

  • Access to Document (DOI)

• Association Between Microscopic Hematuria and Proteinuria Remission in Adult Nephrotic Syndrome.

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

  Kidney medicine 8 ( 5 ) 101333 2026.05

  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 】

• Comparison of Oxford versus Japanese Histological Grading to predict renal function decline in IgA nephropathy: a Japanese prospective cohort study

  Sakaguchi R, Joh K, Honma S, Shimizu A, Hashiguchi A, Katafuchi R, Nishikawa M, Koike K, Hirano K, Tsuboi N, Kawamura T, Yokoo T, Suzuki Y

  Scientific Reports  2026.02

  Joint Work

  • Access to Document (DOI)

• 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

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Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• IgA腎症組織学的重症度分類におけるA/C亜分類の有用性

  本間 志功, 城 謙輔, 坂口 涼子, 橋口 明典, 片渕 律子, 清水 章, 川村 哲也, 横尾 隆, 鈴木 祐介, 下田 将之

  日本病理学会会誌, 

  2026.03

  , 

  (一社)日本病理学会

• NanoCTによる糸球体病変の観察(Observation of Glomerular Lesions Using NanoCT)

  橋口 明典

  日本病理学会会誌, 

  2026.03

  , 

  (一社)日本病理学会

• 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

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• GENERAL PATHOLOGY

  2026

• DISEASES OF ORGAN SYSTEMS

  2026

• GENERAL PATHOLOGY

  2025

• DISEASES OF ORGAN SYSTEMS

  2025

• GENERAL PATHOLOGY

  2024

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Courses Previously Taught 【 Display / hide 】

Courses Previously Taught 【 Display / hide 】

• 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

  2017.04

  -

  2018.03

  , 

  Lecture

• 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