Details of a Researcher - Hashiguchi, Akinori

Papers - Hashiguchi, Akinori

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Intestinal epithelium dysfunctions cause IgA deposition in the kidney glomeruli of intestine-specific Ap1m2-deficient mice.

Yusuke Kinashi, Keisuke Tanaka, Shunsuke Kimura, Masato Hirota, Seiga Komiyama, Tomoko Shindo, Akinori Hashiguchi, Daisuke Takahashi, Shinsuke Shibata, Shin-Ichiro Karaki, Hiroshi Ohno, Koji Hase

EBioMedicine 106 105256 - 105256 2024.08

Joint Work

BACKGROUND: Intestinal epithelial cells (IECs) serve as robust barriers against potentially hostile luminal antigens and commensal microbiota. Epithelial barrier dysfunction enhances intestinal permeability, leading to leaky gut syndrome (LGS) associated with autoimmune and chronic inflammatory disorders. However, a causal relationship between LGS and systemic disorders remains unclear. Ap1m2 encodes clathrin adaptor protein complex 1 subunit mu 2, which facilitates polarized protein trafficking toward the basolateral membrane and contributes to the establishment of epithelial barrier functions. METHODS: We generated IEC-specific Ap1m2-deficient (Ap1m2ΔIEC) mice with low intestinal barrier integrity as an LSG model and examined the systemic impact. FINDINGS: Ap1m2ΔIEC mice spontaneously developed IgA nephropathy (IgAN)-like features characterized by the deposition of IgA-IgG immune complexes and complement factors in the kidney glomeruli. Ap1m2 deficiency markedly enhanced aberrantly glycosylated IgA in the serum owing to downregulation and mis-sorting of polymeric immunoglobulin receptors in IECs. Furthermore, Ap1m2 deficiency caused intestinal dysbiosis by attenuating IL-22-STAT3 signaling. Intestinal dysbiosis contributed to the pathogenesis of IgAN because antibiotic treatment reduced aberrantly glycosylated IgA production and renal IgA deposition in Ap1m2ΔIEC mice. INTERPRETATION: IEC barrier dysfunction and subsequent dysbiosis by AP-1B deficiency provoke IgA deposition in the mouse kidney. Our findings provide experimental evidence of a pathological link between LGS and IgAN. FUNDING: AMED, AMED-CREST, JSPS Grants-in-Aid for Scientific Research, JST CREST, Fuji Foundation for Protein Research, and Keio University Program for the Advancement of Next Generation Research Projects.

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多発病変の中の小さな最高grade病変は,MRIで検出できるのか

松本一宏, 秋田大宇, 橋口明典, 武田利和, 小坂威雄, 福本桂資郎, 安水洋太, 田中伸之, 森田伸也, 水野隆一, 浅沼宏, 大家基嗣, 陣崎雅弘

泌尿器外科 (医学図書出版(株)) 37 ( 8 ) 942 - 944 2024.08

Joint Work, ISSN 0914-6180

Detection of the Highest-Grade Lesion in Multifocal Discordant Prostate Cancer by Multiparametric Magnetic Resonance Imaging.

Kazuhiro Matsumoto, Hirotaka Akita, Akinori Hashiguchi, Toshikazu Takeda, Takeo Kosaka, Keishiro Fukumoto, Yota Yasumizu, Nobuyuki Tanaka, Shinya Morita, Ryuichi Mizuno, Hiroshi Asanuma, Mototsugu Oya, Masahiro Jinzaki

Clinical genitourinary cancer (Clinical Genitourinary Cancer) 22 ( 3 ) 102084 - 102084 2024.06

Joint Work, ISSN 15587673

PURPOSE: Prostate cancer generally occurs multifocally. The lesions of the largest size and highest-grade are often concordant, and defined as an index tumor. However, these factors sometimes do not coincide within one lesion. In such discordant cases, not the largest size lesion but the highest-grade lesion is known to determine the prognosis. We focused on the multiparametric magnetic resonance imaging (mpMRI) detectability of the highest-grade tumors in discordant cases. MATERIALS AND METHODS: We investigated the detectability of the highest-grade tumor using preoperative mpMRI in 50 discordant patients who underwent radical prostatectomy. The radiologist was informed of the tumor location on the pathological tumor map, and mpMRI interpretation for each tumor was performed. RESULTS: Prostate Imaging-Reporting and Data System (PI-RADS) scores of 1, 2, 3, 4, and 5 on preoperative mpMRI were assigned to 13, 1, 9, 16, and 11 of the largest tumors, respectively. On the other hand, scores of 1, 2, 3, 4, and 5 were assigned to 23, 0, 7, 19, and 1 of the highest-grade tumors, respectively. The difference between them was statistically significant (p=0.007). We also found that the largest anterior tumor frequently hid the ipsilateral posterior highest-grade tumor; the detection rate of the highest-grade tumor in this pattern was 42.1% (8 of 19 cases) CONCLUSION: We found that mpMRI detectability of the highest-grade tumor in discordant cases was inferior to that of the largest tumor with low malignant potential. Our results suggest that the risk of high-grade tumors which determine patient prognosis being overlooked.

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慢性腎臓病患者における腎洞脂肪量と腎血行動態の関連の検証

金子賢司, 満野竜之介, 児島大輝, 畔上達彦, 小杉将太郎, 中村俊文, 橋口明典, 山田祥岳, 陣崎雅弘, 山口慎太郎, 伊藤裕, 吉野純, 林香

日本腎臓学会誌 ((一社)日本腎臓学会) 66 ( 4 ) 586 - 586 2024.06

Joint Work, ISSN 0385-2385

Establishment of artificial intelligence model for precise histological subtyping of lung adenocarcinoma and its application to quantitative and spatial analysis.

Miura E., Emoto K., Abe T., Hashiguchi A., Hishida T., Asakura K., Sakamoto M.

Japanese journal of clinical oncology 54 ( 9 ) 1009 - 1023 2024.05

Joint Work, ISSN 0368-2811

BACKGROUND: The histological subtype of lung adenocarcinoma is a major prognostic factor. We developed a new artificial intelligence model to classify lung adenocarcinoma images into seven histological subtypes and adopted the model for whole-slide images to investigate the relationship between the distribution of histological subtypes and clinicopathological factors. METHODS: Using histological subtype images, which are typical for pathologists, we trained and validated an artificial intelligence model. Then, the model was applied to whole-slide images of resected lung adenocarcinoma specimens from 147 cases. RESULT: The model achieved an accuracy of 99.7% in training sets and 90.4% in validation sets consisting of typical tiles of histological subtyping for pathologists. When the model was applied to whole-slide images, the predominant subtype according to the artificial intelligence model classification matched that determined by pathologists in 75.5% of cases. The predominant subtype and tumor grade (using the WHO fourth and fifth classifications) determined by the artificial intelligence model resulted in similar recurrence-free survival curves to those determined by pathologists. Furthermore, we stratified the recurrence-free survival curves for patients with different proportions of high-grade components (solid, micropapillary and cribriform) according to the physical distribution of the high-grade component. The results suggested that tumors with centrally located high-grade components had a higher malignant potential (P < 0.001 for 5-20% high-grade component). CONCLUSION: The new artificial intelligence model for histological subtyping of lung adenocarcinoma achieved high accuracy, and subtype quantification and subtype distribution analyses could be achieved. Artificial intelligence model therefore has potential for clinical application for both quantification and spatial analysis.

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慢性腎臓病患者における腎洞脂肪量と腎血行動態の関連の検証

金子賢司, 満野竜ノ介, 児島大輝, 畔上達彦, 中村俊文, 橋口明典, 山田祥岳, 陣崎雅弘, 山口慎太郎, 伊藤裕, 吉野純, 林香

日本内分泌学会雑誌 ((一社)日本内分泌学会) 100 ( 1 ) 348 - 348 2024.05

Joint Work, ISSN 0029-0661

慢性腎臓病患者における腎洞脂肪量と腎血行動態の関連の検証

金子賢司, 満野竜ノ介, 児島大輝, 畔上達彦, 中村俊文, 橋口明典, 山田祥岳, 陣崎雅弘, 山口慎太郎, 伊藤裕, 吉野純, 林香

日本内分泌学会雑誌 ((一社)日本内分泌学会) 100 ( 1 ) 348 - 348 2024.05

Joint Work, ISSN 0029-0661

Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease.

Kenji Kaneko, Ryunosuke Mitsuno, Daiki Kojima, Tatsuhiko Azegami, Shotaro Kosugi, Toshifumi Nakamura, Akinori Hashiguchi, Yoshitake Yamada, Masahiro Jinzaki, Shintaro Yamaguchi, Hiroshi Itoh, Jun Yoshino, Kaori Hayashi

Obesity research & clinical practice (Obesity Research and Clinical Practice) 18 ( 2 ) 118 - 123 2024.03

Joint Work, ISSN 1871403X

OBJECTIVE: Obesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. METHODS: We evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). RESULTS: RSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = -0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = -0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (β = -0.26, P < 0.001), RRI (β = 0.17, P = 0.022), global glomerular sclerosis (β = 0.21, P = 0.002), and IFTA (β = 0.17, P = 0.012). CONCLUSION: RSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

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Morphological and etiological analyses of C3 and non-C3 glomerulonephritis in primary membranoproliferative glomerulonephritis using periodic acid-methenamine silver stain electron microscopy: a retrospective multicentered study.

Shiko Honma, Naomi Sato, Ryoko Sakaguchi, Akinori Hashiguchi, Noriko Uesugi, Yasuhiro Nakamura, Hironobu Sasano, Kensuke Joh

Medical molecular morphology (Medical Molecular Morphology) 57 ( 1 ) 23 - 34 2024.03

Joint Work, ISSN 18601480

This study elucidated the etiology of C3 glomerulonephritis (C3GN) and non-C3GN with primary membranoproliferative glomerulonephritis (MPGN) using transmission electron microscopy (TEM) and periodic acid-methenamine silver stain (PAM-EM). Thirty-one primary MPGN cases were analyzed by TEM and PAM-EM to distinguish among MPGN I, MPGN II, MPGN III Burkholder subtype (MPGN IIIB), and Anders and Strife subtype (MPGN IIIA/S). Each case was also classified into C3GN or non-C3GN according to the standard C3GN definition using immunostaining. Four cases of MPGN II met C3 glomerulopathy; whereas, four cases of MPGN IIIB did not meet C3 glomerulopathy. Seven of 11 cases (64%) of MPGN I without GBM disruption and 7 of 12 cases (58%) of MPGN IIIA/S with GBM disruption met the non-C3GN criteria with significant immunoglobulins' deposition. Regardless of the C3GN or non-C3GN diagnosis, the deposits in primary MPGN I and MPGN IIIA/S exhibited ill-defined, amorphous, and foggy characteristics similar to those found in postinfectious GN but were different from immune complex (IC) deposits seen in MPGN IIIB. Not only C3GN but also non-C3GN was due to mechanisms other than IC deposition as found in postinfectious GN. Consequently, GBM disruption of MPGN IIIA/S was not due to IC deposition.

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Clinicopathological prognostic stratification for proteinuria and kidney survival in IgA nephropathy: a Japanese prospective cohort study

Kentaro Koike, Tetsuya Kawamura, Keita Hirano, Masako Nishikawa, Akira Shimizu, Kensuke Joh, Ritsuko Katafuchi, Akinori Hashiguchi, Yuichiro Yano, Keiichi Matsuzaki, Masato Matsushima, Nobuo Tsuboi, Shoichi Maruyama, Ichiei Narita, Yokoo Takashi, Yusuke Suzuki

Clinical Kidney Journal (Clinical Kidney Journal) 17 ( 1 ) sfad294 2024.01

Joint Work, ISSN 20488505

BACKGROUND: We require a clinicopathological risk stratification method for immunoglobulin A nephropathy (IgAN) to predict kidney outcomes. We examined a renal failure risk group (RF-RG) classification system created following a prior multicentre, retrospective study to determine if RF-RG could predict kidney outcomes. METHODS: We collected data from Japanese patients with IgAN registered between 1 April 2005 and 31 August 2015. The primary outcome was a composite 50% increase in serum creatinine from baseline or dialysis induction. The secondary outcomes were times to proteinuria remission (ProR) and haematuria remission (HemR). RESULTS: The enrolled 991 patients from 44 facilities were followed for a median of 5.5 years (interquartile range 2.5-7.5), during which 87 composite events (8.8%) occurred. RF-RG was significantly associated with the primary outcome {hazard ratio [HR] II 2.78 [95% confidence interval (CI) 1.12-6.93], III 7.15 (2.90-17.6), IV 33.4 (14.1-79.0), I as a reference, P < .001}.The discrimination performance was good [C-statistic 0.81 (95% CI 0.76-0.86)] and the time-dependent C-statistics exceeded 0.8 over 10 years. Among the 764 patients with proteinuria and 879 patients with haematuria at baseline, 515 and 645 patients showed ProR and HemR, respectively. ProR was significantly less frequent in patients with advanced disease [subdistribution HR: II 0.79 (95% CI 0.67-0.94), III 0.53 (0.41-0.66), IV 0.15 (0.09-0.23), I as a reference, P < .001]. We also observed an association between HemR and RF-RG. CONCLUSIONS: RF-RG demonstrated good predictive ability for kidney outcomes.

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Associations of corticosteroid therapy and tonsillectomy with kidney survival in a multicenter prospective study for IgA nephropathy.

Tetsuya Kawamura, Keita Hirano, Kentaro Koike, Masako Nishikawa, Akira Shimizu, Kensuke Joh, Ritsuko Katafuchi, Akinori Hashiguchi, Keiichi Matsuzaki, Shoichi Maruyama, Nobuo Tsuboi, Ichiei Narita, Yuichiro Yano, Takashi Yokoo, Yusuke Suzuki

Scientific reports (Scientific Reports) 13 ( 1 ) 18455 - 18455 2023.12

Joint Work

Efficacy of systemic corticosteroid therapy (CS) for long-term kidney survival in patients with IgA nephropathy (IgAN) is controversial. Therefore, prospective studies evaluating targeted therapies to lymphatic tissues in mucosal immune system responsible for production of nephritogenic IgA have been desired worldwide. Here, we aimed to evaluate the associations of CS and combination therapy of CS and tonsillectomy (CS + Tx) with kidney survival, using database from a nationwide multicenter prospective cohort study on IgAN. Primary outcome was a 50% increase in serum creatinine from baseline or dialysis induction. The analysis included 941 patients (CS/CS + Tx/non-CS 239/364/338), 85 (9.0%) of whom reached outcomes during median follow-up of 5.5 (interquartile range 2.0-8.0) years. On overlap weighting analysis with balanced baseline characteristics, CS and CS + Tx were associated with lower risk of kidney events when compared with non-CS (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.29-0.88 and HR 0.20, 95%CI 0.09-0.44, respectively). Notably, when compared with the CS, CS + Tx was associated with a lower risk of kidney events (HR 0.40, 95%CI 0.18-0.91). Present study demonstrated, keeping with favorable association of systemic CS with kidney survival, concurrent tonsillectomy as one of targeted interventions to lymphatic tissues may provide additional improvement to kidney survival in patients with IgAN.

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維持透析後のリツキシマブ寛解維持療法継続により血液透析を離脱した重症難治型ANCA関連血管炎の1例

星健太, 村上英人, 小野田怜依, 熊谷光祐, 佐藤由佳, 渡部統, 中村彰良, 橋口明典, 浦井秀徳

日本透析医学会雑誌 ((一社)日本透析医学会) 56 ( 10 ) 377 - 384 2023.10

Joint Work, ISSN 1340-3451

当院において,コントロール不良の2型糖尿病および間質性肺炎を併存する高齢男性に生じた急速進行性糸球体腎炎(rapidly progressive glomerulonephritis:RPGN)で腎生検組織所見から感染後糸球体腎炎合併ANCA関連糸球体腎炎と診断した症例を経験した.プレドニゾロン(prednisolone:PSL)およびリツキシマブ(rituximab:RTX)で寛解導入療法を行うも腎機能が改善せず,維持血液透析療法導入となった.その後の寛解維持療法の継続により重篤な感染症を呈することなくステロイドを投与終了し残存腎機能の回復を認め,RTXの寛解維持治療中に透析導入後11ヵ月で透析離脱となった.高齢かつ合併症の多いANCA関連血管炎におけるRPGNにおいても,腎予後良好な徴候がみられた場合には適切な感染症予防を行ったうえでRTX療法を継続することで透析離脱が可能となる場合がある.(著者抄録)

当院における腎移植後5年の移植腎生検病理組織の検討

坂巻裕介, 香野日高, 橋口明典, 環聡, 桝田司, 高橋遼平, 萩生田純, 徳山博文, 中川健

移植 ((一社)日本移植学会) 58 ( 総会臨時 ) 336 - 336 2023.09

Joint Work, ISSN 0578-7947

慢性糸球体腎炎の臨床経過で腎生検によりmasked IgG kappa depositsを伴う膜性腎症と診断し保存的加療を行った一例

満野竜ノ介, 吉本憲史, 橋口明典, 内山清貴, 山口慎太郎, 林香

日本腎臓学会誌 ((一社)日本腎臓学会) 65 ( 6-E ) 638 - 638 2023.09

Joint Work, ISSN 0385-2385

Hepatitis B Virus-related Membranous Nephropathy with Crescentic Formation in an Inactive Carrier of Positive Hepatitis B Surface Antigen with Undetectable DNA under Anti-viral Treatment: A Case Report.

Kounoue N., Oguchi H., Mikami T., Yamaguchi Y., Hashiguchi A., Nagai H., Watanabe K., Furukawa S., Hisamatsu K., Sakai K.

Internal medicine (Tokyo, Japan) 63 ( 1 ) 101 - 106 2023.05

Joint Work, ISSN 0918-2918

A man who was an inactive hepatitis B virus (HBV) carrier with positive hepatitis B surface antigen (HBs antigen) and undetectable HBV-DNA under anti-viral treatment developed nephrotic syndrome at 52 years old, and a renal biopsy revealed advanced membranous nephropathy (MN) with focal cellular crescents, interstitial hemorrhaging, and peritubular capillaritis. Immunofluorescence studies demonstrated granular IgG deposition and HBs antigen-positivity along the capillaries. Glomeruli were negative for phospholipase A2 receptor 1. There were no clinical findings of systemic vasculitis. We considered MN combined with small-vessel vasculitis due to HBV infection. These results suggest that HBV-related kidney disease should be considered even in patients with an inactive HBV carrier status under treatment.

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IgA腎症におけるステロイド療法,扁摘と腎予後の関連性

平野景太, 川村哲也, 小池健太郎, 西川正子, 清水章, 城謙輔, 片渕律子, 橋口明典, 松崎慶一, 丸山彰一, 坪井伸夫, 成田一衛, 矢野裕一朗, 横尾隆, 鈴木祐介

日本腎臓学会誌 ((一社)日本腎臓学会) 65 ( 3 ) 272 - 272 2023.05

Joint Work, ISSN 0385-2385

J-IGACSを用いたIgA腎症Oxford分類を構成する病変の組み合わせと治療反応性との関連の検討

坂口涼子, 城謙輔, 小此木英男, 中里毅, 橋口明典, 片渕律子, 清水章, 小池健太郎, 平野景太, 坪井伸夫, 川村哲也, 横尾隆, 成田一衛, 鈴木祐介

日本腎臓学会誌 ((一社)日本腎臓学会) 65 ( 3 ) 320 - 320 2023.05

Joint Work, ISSN 0385-2385

J-IGACSを用いたIgA腎症Oxford分類を構成する病変の組み合わせと治療反応性との関連の検討

坂口涼子, 城謙輔, 小此木英男, 中里毅, 橋口明典, 片渕律子, 清水章, 小池健太郎, 平野景太, 坪井伸夫, 川村哲也, 横尾隆, 成田一衛, 鈴木祐介

日本腎臓学会誌 ((一社)日本腎臓学会) 65 ( 3 ) 320 - 320 2023.05

Joint Work, ISSN 0385-2385

IgA腎症におけるステロイド療法,扁摘と腎予後の関連性

日本腎臓学会誌 ((一社)日本腎臓学会) 65 ( 3 ) 272 - 272 2023.05

Joint Work, ISSN 0385-2385

Immunohistochemistry May Not Replace Immunofluorescence in Paraffin-embedded Tissue for Detecting Masked Monoclonal Immunoglobulin Deposits: A Case Report.

Oda Y, Ikeda Y, Abe H, Hashiguchi A, Hatanaka K, Sawai T, Ushiku T, Nangaku M

Internal medicine (Tokyo, Japan) 62 ( 24 ) 3657 - 3661 2023.04

Joint Work, ISSN 0918-2918

An 84-year-old man developed a membranoproliferative glomerulonephritis pattern of injury, and the most likely cause detected during a workup was monoclonal IgG-λ in the urine and serum. Predominant IgG and λ light chain deposition was confirmed only by immunofluorescence using formalin-fixed, paraffin-embedded tissue and not by immunohistochemistry. A smaller and non-linear dynamic range of immunohistochemistry makes it less quantitative than immunofluorescence staining and may explain why immunohistochemistry failed to detect the light chain restriction. This case suggests that immunohistochemistry may not serve as a substitute for immunofluorescence on formalin-fixed, paraffin-embedded tissue in detecting masked monoclonal immunoglobulin deposits, although further research is warranted.

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