Details of a Researcher - Hashiguchi, Akinori

Papers - Hashiguchi, Akinori

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【来たるべくデジタルヘルスケア革命-乗り遅れるな腎臓病学!-】腎臓領域の現在の取り組み腎生検デジタル病理

橋口明典

腎と透析 ((株)東京医学社) 90 ( 2 ) 253 - 259 2021.02

Joint Work, ISSN 0385-2156

【腎非腫瘍性疾患の病理診断の実践-腎生検病理診断から剖検診断まで-】自己免疫疾患に伴う腎障害ループス腎炎を中心に

橋口明典

病理と臨床 ((株)文光堂) 39 ( 2 ) 141 - 147 2021.02

Joint Work, ISSN 0287-3745

【来たるべくデジタルヘルスケア革命-乗り遅れるな腎臓病学!-】臨床現場でのAI活用 AIと病理診断

橋口明典

腎と透析 ((株)東京医学社) 90 ( 2 ) 229 - 235 2021.02

Joint Work, ISSN 0385-2156

A cross-sectional study in patients with IgA nephropathy of correlations between clinical data and pathological findings at the time of renal biopsy: a Japanese prospective cohort study.

Chisako Kamano, Akira Shimizu, Kensuke Joh, Akinori Hashiguchi, Satoshi Hisano, Ritsuko Katafuchi, Tetsuya Kawamura

Clinical and experimental nephrology (Clinical and Experimental Nephrology) 25 ( 5 ) 509 - 521 2021

Research paper (scientific journal), Joint Work, Accepted, ISSN 13421751

BACKGROUND: The correlations between clinical data and pathological findings at the time of renal biopsy were investigated in IgA nephropathy patients. METHODS: 771 patients diagnosed with IgA nephropathy by renal biopsy were enrolled. The correlations between clinical variables including eGFR, daily proteinuria, mean arterial pressure (MAP), serum uric acid (UA) values, and pathological parameters were examined. These patients were further divided into three groups: children (< 19 years old), young adults (19-60 years), and elderly patients (> 60 years). RESULTS: Daily proteinuria was moderately correlated with all pathological parameters (Rs = 0.23-0.49). The mesangial score, the percentage of glomeruli that contained endocapillary hypercellularity, cellular/fibrocellular crescents or tuft necrosis, and segmental glomerulosclerosis (GS) affected daily proteinuria most on multiple linear regression analysis (MLRA). eGFR, MAP, and serum UA levels were mainly correlated with the degree of GS and interstitial lesions. In children, the degree of cellular/fibrocellular crescents or tuft necrosis was correlated with not only daily proteinuria, but also decreased eGFR (Rs = 0.51, - 0.24). Endocapillary hypercellularity was the only independent variable related to daily proteinuria on MLRA. CONCLUSION: In all age cohorts of IgA nephropathy patients, daily proteinuria was correlated with all histological parameters, including both acute and chronic glomerular lesions, and the mesangial score. Independent variables for daily proteinuria were the meangial score, acute histological lesions, and segmental GS on MLRA, whereas the remaining independent variable in the pediatric group was endocapillary hypercellurality. The clinical pathological correlation at the time of biopsy varied depending on the age group.

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A Case of Glomerulonephritis Caused by Bartonella spp. Infective Endocarditis: The Difficulty and Importance of Differentiation from Anti-neutrophil Cytoplasmic Antibody-related Rapidly Progressive Glomerulonephritis.

Ayumi Yoshifuji, Yuuka Hibino, Motoaki Komatsu, Seiichi Yasuda, Koji Hosoya, Emi Kobayashi, Yuko Baba, Shigemichi Hirose, Akinori Hashiguchi, Yoshihiko Kanno, Munekazu Ryuzaki

Internal medicine (Tokyo, Japan) (Internal Medicine) 60 ( 12 ) 1899 - 1906 2021

Research paper (scientific journal), Joint Work, Accepted, ISSN 09182918

A 65-year-old man with valvular disorder presented to his physician because of widespread purpura in both lower extremities. Blood tests showed elevated serum creatinine levels and proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA) with hematuria, suggesting ANCA-related rapidly progressive glomerulonephritis (RPGN). Although multiple blood cultures were negative, transthoracic echocardiography revealed warts in the valves, and a renal biopsy also showed findings of glomerular infiltration by mononuclear leukocytes and C3 deposition in the glomeruli, suggesting infection-related glomerulonephritis. Later, Bartonella antibody turned positive. Antimicrobial treatment improved the purpura and renal function without any recurrence. ANCA-positive RPGN requires the exclusion of infective endocarditis, especially that induced by Bartonella spp.

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Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy

Hayashi K, Hishikawa A, Hashiguchi A, Azegami T, Yoshimoto N, Nakamichi R, Tokuyama H, Itoh H

Scientific Reports (Scientific Reports) 10 ( 1 ) 237 - 237 2020.12

Research paper (scientific journal), Joint Work, Accepted

© 2020, The Author(s). Accumulation of DNA double-strand breaks (DSBs) is linked to aging and age-related diseases. We recently reported the possible association of DNA DSBs with altered DNA methylation in murine models of kidney disease. However, DSBs and DNA methylation in human kidneys was not adequately investigated. This study was a cross-sectional observational study to evaluate the glomerular DNA DSB marker γH2AX and phosphorylated Ataxia Telangiectasia Mutated (pATM), and the DNA methylation marker 5-methyl cytosine (5mC) by immunostaining, and investigated the association with pathological features and clinical parameters in 29 patients with IgA nephropathy. To evaluate podocyte DSBs, quantitative long-distance PCR of the nephrin gene using laser-microdissected glomerular samples and immunofluorescent double-staining with WT1 and γH2AX were performed. Glomerular γH2AX level was associated with glomerular DNA methylation level in IgA nephropathy. Podocytopathic features were associated with increased number of WT1(+)γH2AX(+) cells and reduced amount of PCR product of the nephrin gene, which indicate podocyte DNA DSBs. Glomerular γH2AX and 5mC levels were significantly associated with the slope of eGFR decline over one year in IgA nephropathy patients using multiple regression analysis adjusted for age, baseline eGFR, amount of proteinuria at biopsy and immunosuppressive therapy after biopsy. Glomerular γH2AX level was associated with DNA methylation level, both of which may be a good predictor of renal outcome in IgA nephropathy.

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最大病変が最高Gleason scoreでないmultifocal前立腺癌症例へのGleason scoreの付け方

松本一宏, 橋口明典, 武田利和, 小坂威雄, 高松公晴, 安水洋太, 田中伸之, 森田伸也, 水野隆一, 浅沼宏, 大家基嗣

日本癌治療学会学術集会抄録集 ((一社)日本癌治療学会) 58回 P - 353 2020.10

Research paper (scientific journal), Joint Work, Accepted

腎臓病理所見からT細胞型悪性リンパ腫と診断し得た一例

押田卓磨, 徳山博文, 安田格, 竜崎正毅, 大島洋一, 内山清貴, 橋口明典, 脇野修, 伊藤裕

日本腎臓学会誌 ((一社)日本腎臓学会) 62 ( 6 ) 567 - 567 2020.09

Joint Work, ISSN 0385-2385

多彩な臨床症状を示した顕微鏡的多発血管炎に続発した血栓性微小血管症の1例

坂巻裕介, 小西孝之助, 橋口明典, 松崎達, 香野日高, 中川健, 寺嶋毅, 林晃一

日本腎臓学会誌 ((一社)日本腎臓学会) 62 ( 5 ) 465 - 476 2020.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

症例は70歳代、女性。微熱、頭重感、両大腿のだるさを契機に他院を受診、腎機能障害を指摘され、精査目的で当院を紹介された。血液検査でミエロペルオキシダーゼ抗好中球細胞質抗体(myeloperoxidase anti-neutrophil cytoplasmic antibody:MPO-ANCA)陽性が判明し、腎生検病理所見の結果、血栓性微小血管症(thrombotic microangiopathy:TMA)を合併した顕微鏡的多発血管炎(microscopic polyangiitis:MPA)と診断した。プレドニゾロン(40mg/日)の投与を開始し、ステロイドパルス療法を2クール、静注シクロホスファミドパルス療法(intravenous cyclophosphamide:IVCY)を1クール行った。また、中等度の高血圧を認めたため、ニフェジピンを投与し、血圧コントロールを行った。その後、両下腿浮腫と両側胸水貯留を認めたため、フロセミドを投与した。患者の病状は安定し、入院37日目に退院した。しかし、退院後に、痙攣と夜間に増悪する呼吸困難を認め、うっ血性心不全の診断で再度入院した。入院後、フロセミドを投与したが、尿量の増加は得られず、急速に呼吸状態の悪化を認めたため、気管内挿管後、人工呼吸器を装着した。14時間にわたる持続低効率血液透析(sustained low efficiency dialysis:SLED)を行い、患者の呼吸状態は著明に改善した。抜管後、意識レベルの低下を伴う痙攣を認め、頭部単純CTでは、両側後頭葉に低吸収域を認めたことから、可逆性後頭葉白質脳症(posterior reversible encephalopathy syndrome:PRES)の関与が示唆された。12誘導心電図検査では、経時的にT波の陰転化を認め、心臓超音波検査では、心尖部に限局した壁運動の低下を認めた。冠動脈造影CTでは、血管病変は認めず、たこつぼ心筋症と診断した。本症例は、重篤で多彩な臨床症状を示した、TMAを合併したMPAの1例である。ANCA関連血管炎に続発したTMA症例では免疫抑制療法開始後も注意深い経過観察が必要である。(著者抄録)

デジタル画像解析を用いたIgA腎症腎生検糸球体病変定量化

橋口明典, 石川雅浩, 城謙輔, 坂本直樹, 山内暁, 大塚武, 福西宗憲, 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) 62 ( 4 ) 317 - 317 2020.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

IgA腎症の組織分類の治療選択における有用性の検証

城謙輔, 中里毅, 橋口明典, 清水章, 片渕律子, 川村哲也

日本腎臓学会誌 ((一社)日本腎臓学会) 62 ( 4 ) 265 - 265 2020.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 0385-2385

IgA腎症の組織学的重症度分類に関する亜型分類(A/C)のエヴィデンスに関する前向き多施設共同研究

城謙輔, 橋口明典, 久野敏, 清水章

日本病理学会会誌 ((一社)日本病理学会) 109 ( 1 ) 291 - 291 2020.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0300-9181

腎生検糸球体病変定量化の試み

橋口明典, 石川雅浩, 城謙輔, 清水章, 久野敏, 片渕律子, 川村哲也

日本病理学会会誌 ((一社)日本病理学会) 109 ( 1 ) 435 - 435 2020.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0300-9181

T細胞性悪性リンパ腫の腎浸潤により尿蛋白をきたした一例

押田卓磨, 徳山博文, 橋口明典, 大島洋一, 内山清貴, 脇野修, 伊藤裕

日本内科学会雑誌 ((一社)日本内科学会) 109 ( Suppl. ) 206 - 206 2020.02

Joint Work, ISSN 0021-5384

腎病理で診断に至ったFabry病を背景に多発性骨髄腫を発症したと疑われる一例

安達京華, 徳山博文, 橋口明典, 大島洋一, 伊藤智章, 脇野修, 伊藤裕

日本内科学会雑誌 ((一社)日本内科学会) 109 ( Suppl. ) 206 - 206 2020.02

Joint Work, ISSN 0021-5384

Evaluation of Gleason Grade Group 5 in a Contemporary Prostate Cancer Grading System and Literature Review

Kamitani R, Matsumoto K, Kosaka T, Takeda T, Hashiguchi A, Tanaka N, Morita S, Mizuno R, Shinojima T, Asanuma H, Oya M

Clinical Genitourinary Cancer (Clinical Genitourinary Cancer) 19 ( 1 ) 69 - 75.e5 2020

Research paper (scientific journal), Joint Work, Accepted, ISSN 15587673

© 2020 Elsevier Inc. Introduction: The aim of this study was to validate contemporary grading systems, in particular, the Gleason grade group (GGG) 5. Patients and Methods: We retrospectively reviewed the clinicopathologic data of 176 patients who underwent radical prostatectomy and whose pathologic results were GGG 4 or 5. The endpoints were biochemical recurrence (BCR) and castration-resistant prostate cancer (CRPC). Results: The GGG 4 group was composed of 69 patients. The GGG 5 group consisted of 78 patients with GS 4+5 and 29 patients with GS 5+4 or higher. The 5-year BCR-free survival rates for men with GGG 4, GS 4+5, and GS 5+4 or higher were 59%, 54%, and 20%, respectively, and the 5-year CRPC-free survival rates were 98%, 100%, and 88%, respectively. Both the BCR- and CRPC-free survival rates were significantly higher in GS 4+5 than in GS 5+4 or higher (P < .001 and P = .002, respectively), but there were no significant differences between GGG 4 and GS 4+5 (P = .702 and P = .803, respectively). The multivariate analysis demonstrated that GS 5+4 or higher (hazard ratio, 3.4; P = .002) and lymphovascular invasion (hazard ratio, 3.4; P < .001) greatly affected BCR. Conclusion: Our follow-up study revealed that men with GS 4+5 and those with GGG 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4+5 and GS 5+4 or higher. This suggested that GGG 4 and 5 in the contemporary prostate cancer grading system should be reviewed. Furthermore, lymphovascular invasion may be useful to subgroup these pathologically high-risk patients.

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Maternal undernutrition aggravates renal tubular necrosis and interstitial fibrosis after unilateral ureteral obstruction in male rat offspring

Awazu M, Abe T, Hashiguchi A, Hida M

PLoS ONE (PLoS ONE) 14 ( 9 ) e0221686 2019.09

Research paper (scientific journal), Joint Work, Accepted

© 2019 Awazu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Maternal undernutrition is known to reduce glomerular number but it may also affect tubulointerstitium, capillary density, and response to oxidative stress. To investigate whether the latter elements are affected, we examined the response to unilateral ureteral obstruction (UUO), an established model of renal tubulointerstitial fibrosis, in the kidney of offspring from control and nutrient restricted rats. Six-week old male offspring from rats given food ad libitum (CON) and those subjected to 50% food restriction throughout pregnancy (NR) were subjected to UUO for 7 days. Body weight was significantly lower in NR. Systolic blood pressure and blood urea nitrogen increased similarly in CON and NR after UUO. Tubular necrosis in the obstructed kidney, on the other hand, was more extensive in NR. Also, the collagen area, a marker of fibrosis, of the obstructed kidney was significantly increased compared with the contralateral kidney only in NR. Capillary density was decreased similarly in the obstructed kidney of CON and NR compared with the contralateral kidney. Urine nitrate/ nitrite, a marker of nitric oxide production, from the obstructed kidney was significantly increased in NR compared with CON. Nitrotyrosine, a marker of nitric oxide-mediated free radical injury, was increased in the obstructed kidney compared with the contralateral kidney in both CON and NR, but the extent was significantly greater in NR. In conclusion, more severe tubular necrosis and fibrosis after UUO was observed in NR, which was thought to be due to increased nitrosative stress.

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Fabry病を背景にMyeloma Cast Nephropathyを生じたと疑われる一例

安達京華, 徳山博文, 橋口明典, 大島洋一, 伊藤智章, 脇野修, 伊藤裕

日本腎臓学会誌 ((一社)日本腎臓学会) 61 ( 6 ) 773 - 773 2019.08

Joint Work, ISSN 0385-2385

イムノタクトイド腎症との鑑別が困難であったクリオグロブリン血症性糸球体腎炎の1例

相馬友美, 小杉将太郎, 伊藤智章, 神田武志, 橋口明典, 徳山博文, 脇野修, 伊藤裕

日本腎臓学会誌 ((一社)日本腎臓学会) 61 ( 6 ) 724 - 724 2019.08

Joint Work, ISSN 0385-2385

Acute Interstitial Nephritis With Karyomegalic Epithelial Cells After Nivolumab Treatment—Two Case Reports

Ryuzaki M, Tokuyama H, Uchiyama K, Nakaya H, Hasegawa K, Miyashita K, Konishi K, Hashiguchi A, Wakino S, Itoh H

Clinical Medicine Insights: Case Reports (Clinical Medicine Insights: Case Reports) 12 1179547619853647 - 1179547619853647 2019.06

Research paper (scientific journal), Joint Work, Accepted

© The Author(s) 2019. Clinical application of immune checkpoint inhibitors (CPIs) including nivolumab is expanding in the field of oncology treatment. Nivolumab is an anti-programmed death 1 protein (PD-1) antibody designed to augment an immunologic reaction against cancer cells. On the contrary, CPIs are known to cause a unique variety of side effects termed as immune-related adverse events, which can affect any organ including kidney. However, the characteristics of renal disorders by nivolumab treatment are poorly described. We describe two cases of acute kidney injury that were treated with nivolumab. Two patients, one with renal-cell carcinoma and the other with lung cancer, exhibited progressive renal dysfunction after the initiation of nivolumab treatment. By kidney biopsy, each case was diagnosed as acute interstitial nephritis (AIN). Of note, tubular epithelial cells enlarged with hyperchromatic nuclei were focally observed, and this finding was consistent with karyomegalic tubular epithelial cells. In immunostaining, most of the enlarged tubular epithelial cells were positive for Ki-67, which suggested regeneration of tubular epithelial cells. Clinically, in one case, re

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