論文 - 橋口　明典

A girl with membranous nephropathy associated with ventriculoperitoneal shunt infection.

Awazu M, Miyahara M, Chiga M, Hashiguchi A, Takahashi H

CEN case reports （CEN case reports）  12 （ 1 ） 130 - 134 2022年09月

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　概要を見る

Glomerulopathy associated with shunt infection is commonly membranoproliferative glomerulonephritis, whereas the causative organisms of secondary membranous nephropathy are usually viruses. We report a case of membranous nephropathy associated with shunt infection. The patient was born at 29-week gestation with a birth weight of 1178 g. Ventriculoperitoneal shunt surgery had been performed for congenital hydrocephalus. Thereafter, she had experienced seven shunt infections. At the age 13 years, proteinuria was detected in a school urinary screening. Urinalysis at our hospital demonstrated 3 + protein and 3 + blood. Laboratory testing demonstrated a serum creatinine 0.5 m/dl, albumin 2.5 g/dl, C-reactive protein (CRP) 13.7 mg/dl, and C3 182 mg/dl. Prior to repeat urinalysis, the patient developed vomiting and was admitted with suspected shunt infection. On admission, her body temperature was 36.0 ºC. Physical examination was unremarkable other than small stature and a palpable mass in the left upper quadrant. Urinalysis demonstrated 2 + protein and 1 + blood with no cells or casts. The urinary protein excretion was 3 g/day. Abnormal laboratory tests included erythrocyte sedimentation rate 102 mm/hr, CRP 11.67 mg/dl, IgG 2442 mg/dl, C3 177 mg/dl, and C4 44 mg/dl. Antibiotic therapy was initiated for a presumptive diagnosis of shunt infection and the shunt catheter was removed. Cultures obtained after antibiotic administration were negative. Proteinuria persisted after control of the shunt infection. Histology of a renal biopsy demonstrated membranous nephropathy with diffuse granular IgG staining and subepithelial deposits. Three possible pathomechanisms for her membranous nephropathy were considered.

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Structural modeling for Oxford histological classifications of immunoglobulin A nephropathy

Joh K., Nakazato T., Hashiguchi A., Shimizu A., Katafuchi R., Okonogi H., Koike K., Hirano K., Tsuboi N., Kawamura T., Yokoo T., Narita I., Suzuki Y.

PLoS ONE （PLoS ONE）  17 （ 9 September ） e0268731 2022年09月

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　概要を見る

In immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria, eGFR, mean arterial pressure (MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy (ST) and renin-angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the model's goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity and active crescent (C) had an attenuating indirect effect via ST. Segmental sclerosis (S) had an attenuating indirect effect via eGFR and mesangial hypercellularity (M) had accelerative indirect effect for RFD via proteinuria. Moreover, M and C had accelerative indirect effect via proteinuria, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR or MAP at biopsy, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.

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キャッスルマン病で治療中に壊死性筋膜炎及び急性腎障害を呈した2型糖尿病患者の1例

山口 慎太郎, 安達 京華, 吉本 憲史, 安田 格, 内山 清貴, 田島 敬也, 吉野 純, 橋口 明典, 神田 武志, 目黒 周, 伊藤 裕

糖尿病 （(一社)日本糖尿病学会）  65 （ 7 ） 395 - 395 2022年07月

共著,  ISSN  0021-437X

興味深い経過をたどった糖尿病性胃腸症の1例

鍛治場 寛, 村田 祥磨, 生形 晃男, 清水 彩, 北川 清宏, 野田 まりん, 久武 祐太, 野島 淳, 橋口 明典, 寺元 研, 東澤 俊彦, 関根 忠一, 岡村 幸重

日本消化器病学会関東支部例会プログラム・抄録集 （日本消化器病学会-関東支部）  370回   25 - 25 2022年07月

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Diagnosis of monoclonal immunotactoid glomerulopathy with positive λ chain by immunoelectron microscopy.

Sugita E, Sonoda H, Ryuzaki M, Hashiguchi A, Tokuyama H, Wakino S, Kanda T, Itoh H

CEN case reports （CEN case reports）  12 （ 1 ） 7 - 13 2022年06月

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We report the case of a 73-year-old-man who developed immunotactoid glomerulopathy (ITG). ITG is a rare disease characterized by proliferative glomerulonephritis and capillary wall deposits with a 10-60 nm diameter microtubular substructure. In monoclonal ITG, immunofluorescence analysis typically exhibits IgG with light chain restriction. Recent reviews recommend distinguishing monoclonal ITG from polyclonal ITG because monoclonal ITG is associated with a higher incidence of hematological disorders and better responsiveness to clone-directed therapy and renal prognosis. In our case, IgG, IgA, and IgM were negative by routine immunofluorescence; however, immunoelectron microscopy revealed positive λ chain. At 6 months after renal biopsy, the IgG λ chain was detected in the serum and urine, reflecting possible monoclonality. Therefore, it is useful to perform immunoelectron microscopy and follow-up with serum and urine protein electrophoresis and immunofixation to diagnose monoclonal ITG, even when routine immunofluorescence shows negative or nonspecific findings.

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MPO-ANCA、抗GBM抗体共陽性かつ膜性腎症を合併した急速進行性糸球体腎炎に対して選択的血漿交換(SePE)を行った一例

星 健太, 浦井 秀徳, 渡部 統, 中村 彰良, 橋口 明典, 村上 円人

日本急性血液浄化学会雑誌 （(NPO)日本急性血液浄化学会）  13 （ 1 ） 48 - 51 2022年06月

共著,  ISSN  2185-1085

　概要を見る

当院において、半月体形成性糸球体腎炎を呈したMPO-ANCA、抗糸球体基底膜(glomerular basement membrane:GBM)抗体共陽性かつ膜性腎症を合併した急速進行性糸球体腎炎(rapidly progressive glomerulonephritis:RPGN)を経験した。血清Crの上昇がみられた早期に副腎皮質ステロイド、静注シクロホスファミドパルス療法(intravenous cyclophosphamide:IVCY)に加え選択的血漿交換(selective plasma exchange:SePE)を行ったところ、2抗体の陰性化を得られ肺障害を生じることなく腎機能障害も改善した。発症早期に、免疫抑制療法に加えて凝固因子補充不要なSePEを行うことが新規抗体産生抑制および抗体除去に有用であると考えられた。(著者抄録)

【IgA腎症-最新の知見】腎生検組織標本へのAIの活用

橋口 明典

腎と透析 （(株)東京医学社）  92 （ 6 ） 1072 - 1076 2022年06月

共著,  ISSN  0385-2156

Clinical and pathological characteristics of patients with acute kidney injury in Japan in whom kidney biopsy was performed: a cross-sectional analysis of the Japan Renal Biopsy Registry (J‑RBR).

Moniwa N, Tanaka M, Sato H, Shimizu A, Sugiyama H, Yokoyama H, Tsuruya K, Hashiguchi A, Committee for Renal Biopsy and Disease Registry of the Japanese Society of Nephrology.

Clinical and experimental nephrology （Clinical and Experimental Nephrology）  26 （ 10 ） 963 - 973 2022年05月

共著,  ISSN  1342-1751

　概要を見る

Introduction: Acute kidney injury (AKI) is a worldwide concern and it leads to a poor prognosis or end-stage kidney disease. The purpose of this study was to clarify the characteristics of patients with AKI in whom kidney biopsy was performed using data of the Japan Renal Biopsy Registry (J-RBR). Methods: We screened 38,351 cases that were registered in the J-RBR from 2007 to 2018. We obtained data for 383 patients with AKI based on clinical diagnosis for analysis 1 and data for 714 patients with acute interstitial nephritis (AIN) or acute tubular necrosis (ATN) based on pathological diagnosis for analysis 2. Results: Of the cases screened, 383 patients with AKI (1.0%) were included in analysis 1. The main pathological diagnoses of AKI were AIN, ATN, chronic interstitial nephritis, nephro-sclerosis and crescentic glomerulonephritis. Of the cases screened, 589 patients with AIN (1.5%) and 110 patients with ATN (0.3%) were included in analysis 2. The main clinical diagnoses of AIN were AKI, rapidly progressive glomerulonephritis (RPGN), chronic nephritic syndrome (CNS) and drug-induced nephropathy (DIN), whereas those of ATN were AKI, RPGN, DIN and CNS. ATN patients had a higher serum creatinine level than that of AIN patients. Conclusion: Our results revealed that cases in the J-RBR included 1.0% of AKI cases based on clinical diagnosis and 1.5% and 0.3% of AIN and ATN cases, respectively, based on pathological diagnosis. In patients with suspected intrinsic AKI, kidney biopsy should be performed for diagnosis of the precise etiology and selection of appropriate treatment.

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無症候性血尿で経過観察中にSARS-CoV-2ワクチンによる肉眼的血尿を伴いIgA腎症と診断した2例

森澤 和美, 高橋 努, 濱田 陸, 幡谷 浩史, 本田 尭, 三上 直朗, 松岡 健太郎, 緒方 謙太郎, 山中 真理子, 尾原 健太郎, 橋口 明典, 本田 雅敬

日本小児腎臓病学会雑誌 （(一社)日本小児腎臓病学会）  35 （ 1Suppl. ） 156 - 156 2022年04月

共著,  ISSN  0915-2245

異なる撮像機のデジタルスライドに対して抗酸菌検出AIの再現性を得るための検討

江本 桂, 松田 紘典, 阿部 時也, 橋口 明典, 坂元 亨宇

日本病理学会会誌 （(一社)日本病理学会）  111 （ 1 ） 240 - 240 2022年03月

共著,  ISSN  0300-9181

当院で施行した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, 萩生田 純, 桝田 司, 宍戸 偉海, 井上 博之, 徳山 博文, 中川 健

日本臨床腎移植学会プログラム・抄録集 （(一社)日本臨床腎移植学会）  55回   288 - 288 2022年02月

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Quantitative evaluation of color difference between actual specimens and whole-slide imaging-scanned images calibrated with commercial color charts

Murayama Y., Sugiyama T., Ogino Y., Furuta H., Kambara T., Kamisono K., Abe T., Emoto K., Hashiguchi A., Kajimura Y., Sakamoto M.

Progress in Biomedical Optics and Imaging - Proceedings of SPIE （Progress in Biomedical Optics and Imaging - Proceedings of SPIE）  12039 2022年

共著,  ISSN  16057422

　概要を見る

When using different cameras and displays in the shot and display of one subject, different color images are often showed. To solve this problem, we have developed a color chart in which the constituent colors dyed with dyes are evenly distributed in the color space. We have also developed a tool that creates an International Color Consortium (ICC) profile from the captured image of this color chart. In this report, we will describe the color difference correction accuracy when our method is applied to actual stained pathological specimens taken with multiple whole-slide imaging (WSI). We confirmed color correction accuracy of Lab values in major parts such as the cell nucleus. The Lab value of the specimen itself measured by a spectrocolorimeter was compared with that of the captured image. As a result, the color difference ?E in H&E-stained cell nucleus was improved from 32.2 to 6.4 for Nanozoomer and from 13.5 to 7.2 for ultra-fast scanner (UFS) by our color correction. The results of the evaluations for other areas and other stain methods (PAS, EVG, MT, and PAM) were good. In the future, high-accuracy color correction of teacher data/evaluation data in AI diagnosis using pathological images will be important.

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DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation

Hishikawa A., Hayashi K., Kubo A., Miyashita K., Hashiguchi A., Kinouchi K., Yoshimoto N., Nakamichi R., Akashio R., Sugita E., Azegami T., Monkawa T., Suematsu M., Itoh H.

iScience （iScience）  24 （ 12 ） 103436 - 103436 2021年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2589-0042

　概要を見る

The “preconditioning effect” in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5.

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A Case of Fibronectin Glomerulopathy Confused with Glomerular Endothelial Injury in a Patient with Takotsubo Cardiomyopathy.

Azegami T, Hashiguchi A, Nakayama T, Hayashi K, Kanda T, Itoh H

Internal medicine (Tokyo, Japan) （Internal Medicine）  61 （ 13 ） 2027 - 2032 2021年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0918-2918

　概要を見る

A 46-year-old woman developed takotsubo cardiomyopathy and nephrotic syndrome. The first kidney biopsy suggested non-immune-complex-mediated membranoproliferative glomerulonephritis (MPGN), and she was diagnosed with glomerular endothelial injury associated with takotsubo cardiomyopathy. A second biopsy was performed two years later because of persistent proteinuria despite renin-angiotensin system inhibition. This biopsy indicated non-immune-complex-mediated MPGN, but a mesangial and subendothelial substance of a higher electron density than that in the first biopsy was detected, suggesting the possibility of glomerular disease with non-immune deposits rather than endothelial injury. Finally, she was diagnosed with fibronectin nephropathy. Although rare, fibronectin glomerulopathy should be considered in non-immune-complex-mediated MPGN.

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Diabetic condition induces hypertrophy and vacuolization in glomerular parietal epithelial cells

Kawaguchi T., Hasegawa K., Yasuda I., Muraoka H., Umino H., Tokuyama H., Hashiguchi A., Wakino S., Itoh H.

Scientific Reports （Scientific Reports）  11 （ 1 ） 1515 - 1515 2021年12月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Diabetic nephropathy (DN) is accompanied by characteristic changes in the glomerulus, but little is known about the effect of diabetes on parietal epithelial cells (PECs). In this study, a descriptive analysis of PECs was undertaken in diabetic db/db mice and in diabetic patients. PEC hypertrophy was significantly more prominent in diabetic mice than in nondiabetic mice, and this was evident even at the early stage. Additionally, the number of vacuoles in PECs was markedly increased in diabetic mice, suggesting the presence of cellular injury in PECs in DN. Although rare, binuclear cells were observed in mice with early diabetes. In cultured PECs, a high glucose condition, compared with normal glucose condition, induced cellular hypertrophy and apoptosis. Flow cytometry showed that some PECs in the G0 phase reentered the cell cycle but got arrested in the S phase. Finally, in human diabetic subjects, hypertrophy and vacuolization were observed in the PECs. Our data showed that PECs undergo substantial changes in DN and may participate in rearrangement for differentiation into podocytes.

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手術標本および生検標本のH&E染色組織画像を用いた畳み込みニューラルネットワークによる肝細胞癌の識別

高木 弦, 山口 雅浩, 阿部 時也, 橋口 明典, 坂元 亨宇

日本医用画像工学会大会予稿集 （(一社)日本医用画像工学会）  40回   133 - 137 2021年10月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

本研究では,H&E染色病理標本のデジタルスライド画像に対して畳み込みニューラルネットワーク(CNN)による肝細胞癌と非癌の識別を行った.CNNとしてEfficientNetB3を採用し,高解像度の病理画像を分割して学習させ,その結果を統合する方法について検討するとともに,学習率などについて改善行い精度向上を図った.2048×2048画素の手術標本及び生検標本の画像それぞれ約1,000枚に対して5-foldの交差検証を行った結果,先行研究において特徴量ベースのSVMで約90%の精度であったデータに対して,正解率約97%と極めて高い精度を得ることかができた.このとき,生検標本と手術標本の両者の画像を合わせて教師データとした際に,高精度でロバストな識別器が作成できることが示された.さらに,生検標本と手術標本の両方を学習させた際に,CNNが両者に共通する特徴を抽出しているのかについても考察を行った.(著者抄録)

Fabry disease associated with multiple myeloma: a case report.

Keika Adachi, Hirobumi Tokuyama, Yoichi Oshima, Tomoaki Itoh, Akinori Hashiguchi, Hiroyuki Yamakawa, Tadayasu Togawa, Hitoshi Sakuraba, Shu Wakino, Hiroshi Itoh

CEN case reports （CEN case reports）  11 （ 1 ） 146 - 153 2021年09月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

Fabry disease (FD) is an X-linked genetic lysosomal disorder caused by alpha-galactosidase A (GLA) deficiency. Multiple myeloma (MM) predominately affects older adults, which ranks as the second commonest hematological malignancy. Their overlap has rarely been reported. We present a case of the coexistence of FD and MM in a patient. We report the case of a 68-year-old woman who was referred to our hospital for the evaluation of thoracic spine tumor with bone destruction. On admission, her serum creatinine (Cr) level was elevated to 12.70 mg/dL from the baseline value of 0.91 mg/dL. Bone marrow aspiration revealed MM. Renal biopsy showed myeloma cast nephropathy, which was the primary cause of acute kidney injury. Renal pathology also showed podocyte swelling and tubule myeloid bodies in a mosaic pattern compatible with female FD. Consequently, the patient was diagnosed as FD based on the germ line mutation in GLA. The patient was treated with bortezomib and dexamethasone therapy, which significantly improved the renal function. This is the second case demonstrating a potential pathogenic relationship between FD and MM. Since FD is one of the few genetic diseases for which there are therapeutic agents with fewer side effects, diagnostic value of FD is high. If an MM patient has multiple organ abnormalities or any familial history, the physician should suspect FD.

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Undifferentiated carcinoma of the mandible detected simultaneously with the liver: A case report

Asoda S., Morita M., Soma T., Sato H., Hasegawa T., Nakagawa T., Hashiguchi A., Kawana H.

Oral and Maxillofacial Surgery Cases （Oral and Maxillofacial Surgery Cases）  7 （ 3 ） 100228 - 100228 2021年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2214-5419

　概要を見る

We herein report a rare case of undifferentiated carcinoma that originated in the mandible with the same pathological findings as seen in the liver. A 64-year-old man underwent surgery for a hepatic tumor in October 2006, and the pathological diagnosis was undifferentiated carcinoma. The patient was referred to our department in January 2007, when whole-body positron emission tomography/computed tomography showed the uptake of fluorodeoxyglucose in the right mandibular ramus. The patient underwent right hemimandibulectomy in April 2007. The resected tumor was also undifferentiated carcinoma. In May 2014, seven years after the lower mandibular operation, the tumor recurred at the site corresponding to the right mandibular ramus after resection, and tumor resection and right neck dissection were performed. As a result of the histopathological examination, the undifferentiated carcinoma findings were the same as before. There have been no signs of local recurrence or metastases for over six years since the second mandibular surgery.

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MPGN様の病理像を呈したλ鎖単独陽性イムノタクトイド腎症の一例

杉田 絵里那, 神田 武志, 竜崎 正毅, 橋口 明典, 林 香, 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）  63 （ 6-E ） 739 - 739 2021年09月

共著,  ISSN  0385-2385

たこつぼ心筋症の発症後に、内皮細胞障害との鑑別を要したフィブロネクチン腎症の1例

畔上 達彦, 中山 尭振, 林 香, 橋口 明典, 神田 武志, 伊藤 裕

日本腎臓学会誌 （(一社)日本腎臓学会）  63 （ 6-E ） 685 - 685 2021年09月

共著,  ISSN  0385-2385