論文 - 橋口　明典

IgA血管炎と鑑別を要した本態性クリオグロブリン血症性糸球体腎炎の一例

堤 遼太郎, 大島 洋一, 中村 彰良, 杉浦 康平, 圓谷 泰章, 杉原 晋之介, 加藤 亜唯, 橋口 明典, 小松 素明

日本腎臓学会誌 （(一社)日本腎臓学会）  65 （ 6-E ） 607 - 607 2023年09月

共著,  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年05月

共著,  ISSN  0918-2918

　概要を見る

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.

• Access to Document (DOI)

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年05月

共著,  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年05月

共著,  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年05月

共著,  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

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年05月

共著,  ISSN  0385-2385

短腸症候群による二次性オキサローシスが腎機能障害の原因と考えられた1例

熊谷 聡佑, 川口 隆久, 有馬 功一郎, 橋口 明典, 高木 英恵, 野崎 博之, 安藤 孝

日本内科学会関東地方会 （日本内科学会-関東地方会）  686回   48 - 48 2023年05月

共著

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年04月

共著,  ISSN  0918-2918

　概要を見る

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.

• Access to Document (DOI)

DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation

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 （ 4 ） 112302 - 112302 2023年04月

共著

　概要を見る

Recent epigenome-wide studies suggest an association between blood DNA methylation and kidney function. However, the pathological importance remains unclear. Here, we show that the homing endonuclease I-PpoI-induced DNA double-strand breaks in kidney glomerular podocytes cause proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis with DNA methylation changes in blood cells as well as in podocytes. Single-cell RNA-sequencing analysis reveals an increase in cytotoxic CD8+ T cells with the activating/costimulatory receptor NKG2D in the kidneys, which exhibit a memory precursor effector cell phenotype, and the CD44high memory CD8+ T cells are also increased in the peripheral circulation. NKG2D blockade attenuates the renal phenotype caused by podocyte DNA damage. Blood methylome shows increased DNA methylation in binding sites for STAT1, a transcription factor contributing to CD8+ T cell homeostasis. Collectively, podocyte DNA damage alters the blood methylome, leading to changes in CD8+ T cells, which contribute to sustained renal injury in chronic kidney disease.

• Access to Document (DOI)

Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria

Yoshimoto N., Hayashi K., Hishikawa A., Hashiguchi A., Nakamichi R., Sugita-Nishimura E., Yoshida-Hama E., Azegami T., Nakayama T., Itoh H.

Hypertension Research （Hypertension Research）  46 （ 4 ） 1000 - 1008 2023年04月

共著,  ISSN  09169636

　概要を見る

The number of chronic kidney disease (CKD) patients is increasing worldwide, and it is necessary to diagnose CKD patients in earlier stages to improve their prognosis. Previously, in a study using human samples, we reported that DNA methylation and DNA damage in podocytes are potential markers for kidney function decline in IgA nephropathy; however, these candidate markers have not been adequately investigated in other glomerular diseases. Here, we report that the association of podocyte DNA damage and DNA methylation with eGFR decline and proteinuria differs depending on the type of glomerular disease. Patients diagnosed with minor glomerular abnormality (MGA, n = 33), membranous nephropathy (MN, n = 9) or diabetic nephropathy (DN, n = 10) following kidney biopsy at Keio University Hospital from 2015 to 2017 were included. In MGA patients, both podocyte DNA damage and glomerular DNA methylation were associated with the severity of proteinuria. In DN patients, podocyte DNA double-strand breaks (DSBs) and glomerular DNA methylation were associated with an eGFR decline. When patients with urinary protein levels of more than 1 g/gCr were examined, fewer podocyte DNA DSBs were detected in MN patients than in MGA patients, and the level of glomerular DNA methylation was lower in MN patients than in MGA or DN patients. These results indicate that investigating podocyte DNA DSBs and DNA methylation changes may be useful for understanding the pathogenesis of CKD with proteinuria in humans. [Figure not available: see fulltext.].

• Access to Document (DOI)

Case report: Importance of early and continuous tocilizumab therapy in nephrotic syndrome associated with idiopathic multicentric Castleman disease: A case series

Kojima D., Yamaguchi S., Hashiguchi A., Hayashi K., Uchiyama K., Yoshimoto N., Adachi K., Nakayama T., Nishioka K., Tajima T., Morimoto K., Yoshino J., Yoshida T., Monkawa T., Kanda T., Itoh H.

Frontiers in Medicine （Frontiers in Medicine）  9   1037032 - 1037032 2023年01月

共著,  ISSN  2296-858X

　概要を見る

Idiopathic multicentric Castleman disease (iMCD) is a systemic and polyclonal lymphoproliferative disease involving multiple organs, including the kidneys, due to the overproduction of interleukin-6 (IL-6). Recently, several reports have suggested that excessive IL-6 actions in iMCD could have a causal relationship with the development of diverse histopathological renal manifestations that cause nephrotic syndrome. However, the treatment for such cases remains unclear. We report a series of three cases of nephrotic syndrome due to iMCD that helps to delineate the importance of early and continuous therapy with the anti-interleukin-6 receptor antibody tocilizumab. First, treatment was suspended for infectious control, and the patient presented with nephrotic syndrome due to diffuse mesangial and endocapillary hypercellularity without immune deposits complicating acute kidney injury. Second, iMCD was treated with prednisolone alone. The patient suddenly developed nephrotic syndrome due to immune-complex glomerulonephritis, not otherwise specified, complicated with acute kidney injury. In the third case, nephrotic syndrome secondary to membranous glomerulonephritis was diagnosed, with a skin rash and IgE antibodies to tocilizumab, and was therefore treated with prednisolone alone. In contrast to the first two cases, the third progressed to end-stage renal disease on hemodialysis. Taken together, this series suggests that clinicians should maintain clinical vigilance for iMCD as a possible underlying component of nephrotic syndrome, since iMCD presents with a variety of renal pathologies. Prompt initiation and continuous administration of tocilizumab are likely key determinants of renal outcomes in such cases. In particular, when tocilizumab is suspended due to infection or in the perioperative period, consideration of its expeditious resumption should be made, taking into account both the withdrawal period and systemic conditions.

• Access to Document (DOI)

Antineutrophil cytoplasmic antibody-associated vasculitis predominantly manifesting tubulointerstitial nephritis: A case report

Nishioka K., Yamaguchi S., Hashiguchi A., Yoshimoto N., Tajima T., Yasuda I., Uchiyama K., Kaneko K., Aso M., Yoshino J., Monkawa T., Kanda T., Hayashi K., Itoh H.

SAGE Open Medical Case Reports （SAGE Open Medical Case Reports）  11   2050313X231197324 2023年01月

共著,  ISSN  2050-313X

　概要を見る

The common histopathology of antineutrophil cytoplasmic antibody-associated vasculitis comprises pauci-immune crescentic glomerulonephritis with concomitant tubulointerstitial nephritis. Tubulointerstitial nephritis in the absence of glomerular involvement in patients with antineutrophil cytoplasmic antibody-associated vasculitis is uncommon. We report a case of antineutrophil cytoplasmic antibody-associated vasculitis-associated acute kidney injury manifesting as tubulointerstitial nephritis without glomerulonephritis. A 75-year-old woman with fever, cough, and myalgia developed kidney dysfunction with inflammatory reactions and tubular-type proteinuria, without glomerular hematuria. A kidney biopsy revealed tubulointerstitial nephritis with arteritis. We ruled out important underlying etiologies of tubulointerstitial nephritis, including infection, drug reactions, and autoimmune diseases. Since chest high-resolution computed tomography demonstrated mild interstitial pneumonia in bilateral lower lung fields, myeloperoxidase antineutrophil cytoplasmic antibody was measured and found to be positive. Therefore, we diagnosed the patient with antineutrophil cytoplasmic antibody-associated vasculitis-associated tubulointerstitial nephritis but not glomerulonephritis, and interstitial pneumonia. The patient’s kidney function and symptoms markedly improved with prednisolone treatment. Clinicians should maintain high-level vigilance for antineutrophil cytoplasmic antibody-associated vasculitis as a possible underlying component of tubulointerstitial nephritis, particularly when kidney function deteriorates with tubulointerstitial injuries without glomerular features.

• Access to Document (DOI)

Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report

Kohatsu K., Suzuki T., Takimoto M., Matsui K., Hashiguchi A., Koike J., Shirai S.

BMC Nephrology （BMC Nephrology）  23 （ 1 ） 367 2022年12月

共著

　概要を見る

Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3+ regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency. Case presentation: A 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4+ T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents. Conclusions: There have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.

• Access to Document (DOI)

肺炎球菌性菌血症で発見されたC3 nephritic factor陽性のC3腎炎/MPGNの7歳女児

森下 俊真, 遠藤 翔太, 武政 洋一, 大貫 裕太, 櫻谷 浩志, 村上 仁彦, 藤永 周一郎, 橋口 明典

日本小児腎臓病学会雑誌 （(一社)日本小児腎臓病学会）  35 （ 2 ） 175 - 176 2022年11月

共著,  ISSN  0915-2245

寛解後もC3低値が持続し追跡腎生検でC3NeF陽性C3腎炎と診断した1例

荒尾 正人, 飛田和 えりか, 吉村 萌, 秋岡 祐子, 橋口 明典

日本小児腎臓病学会雑誌 （(一社)日本小児腎臓病学会）  35 （ 2 ） 175 - 175 2022年11月

共著,  ISSN  0915-2245

尿細管・間質病変主体のANCA関連血管炎の一例

西岡 謙, 山口 慎太郎, 安田 格, 吉本 憲史, 田島 敬也, 林 香, 吉野 純, 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）  64 （ 6-E ） 549 - 549 2022年10月

共著,  ISSN  0385-2385

間質にIgM-λ陽性の沈着物を認めたprimary renal lymphomaの一例

川口 隆久, 唐澤 隆明, 橋口 明典, 大嶋 洋佑, 渡辺 雄祐, 熊谷 聡佑, 有馬 功一郎, 安藤 孝

日本腎臓学会誌 （(一社)日本腎臓学会）  64 （ 6-E ） 550 - 550 2022年10月

共著,  ISSN  0385-2385

膜性腎症とMPO-ANCA関連血管炎を合併した高齢男性の1例

野間 悠太朗, 竜崎 正毅, 田島 敬也, 伊藤 亘, 松本 朋美, 坂口 知広, 森田 洋平, 貫井 紀宏, 池上 良, 橋口 明典, 久保田 英司

日本腎臓学会誌 （(一社)日本腎臓学会）  64 （ 6-E ） 570 - 570 2022年10月

共著,  ISSN  0385-2385

妊娠末期に発症した膜性腎症の1例

伊藤 智章, 中村 健吾, 篠塚 圭祐, 二木 功治, 緒方 謙太郎, 橋口 明典

日本腎臓学会誌 （(一社)日本腎臓学会）  64 （ 6-E ） 563 - 563 2022年10月

共著,  ISSN  0385-2385

腎臓の間質にIgM-λ陽性の沈着物を認めた低悪性度B細胞リンパ腫の一例

川口 隆久, 唐澤 隆明, 橋元 奈津子, 橋口 明典, 熊谷 聡佑, 有馬 功一郎, 安藤 孝

神奈川腎炎研究会抄録集 （神奈川腎炎研究会）  79回   np93 - np114 2022年10月

共著