総合医科学研究所　遺伝子発見機構学
  1. 研究者リスト
  2. 坪井 直毅

坪井 直毅

ツボイ ナオタケ  (Naotake Tsuboi)

基本情報

所属
藤田医科大学 医学部腎臓内科学 教授
学位
医学博士(名古屋大学)
J-GLOBAL ID
201001034860762065
researchmap会員ID
1000314029

経歴

 16
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学歴

 2

委員歴

 1

受賞

 1

論文

 154
  • Takahiro Kato, Tomohiro Mizuno, Takenao Koseki, Kazuo Takahashi, Shigeki Yamada, Kazuyoshi Imaizumi, Naotake Tsuboi, Naozumi Hashimoto
    Fujita medical journal 11(3) 129-134 2025年8月  
    OBJECTIVES: Sivelestat sodium hydrate (SSH) may be effective in the early stage of acute respiratory distress syndrome (ARDS) before the neutrophil extracellular trap scaffold structure is complete. Therefore, patients with suppression of fibrinolysis (SF) before the secondary fibrinolytic process might benefit from SSH administration. The primary aim of this study was to determine the effect of the SF state and combination therapy on the effect of SSH administration. METHODS: We retrospectively reviewed the data of patients diagnosed with ARDS at Fujita Health University Hospital between July 2005 and December 2016. Patients with ARDS were stratified into the SF and hyperfibrinolysis (HF) groups. Using the fibrin degradation product (FDP)/D-dimer ratio, cut-off values were set as follows: FDP/D-dimer >2 for the HF group and FDP/D-dimer ≤2 for the SF group. The 28-day mortality was the primary endpoint. RESULTS: In total, 168 patients (71 in the HF group and 97 in the SF group) were included in the analysis. The mortality within 28 days was not different based on SSH administration in either group (HF group: p=0.956, SF group: p=0.957). In the SF group, the mortality rate within 28 days in SSH-treated patients who received antithrombotic drugs was significantly higher than that in patients who received SSH only (p<0.05). However, this finding was not present in the HF group (p=0.786). CONCLUSIONS: Concomitant use of SSH and antithrombotic drugs might worsen the treatment outcome of patients with ADRS in the SF state.
  • Masaya Hirayama, Yukako Ohyama, Yudai Tsuji, Tetsuro Enomoto, Midori Hasegawa, Naotake Tsuboi, Jan Novak, Kazuo Takahashi
    Clinical and experimental nephrology 2025年4月7日  
    BACKGROUND: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis. Elevation in the blood levels of aberrantly glycosylated IgA1 is a crucial initial step in IgAN pathogenesis. Here, we aimed to determine the longitudinal changes in the serum levels of IgA1 O- and N-glycoforms in patients with IgAN receiving different treatments. METHODS: We enrolled Japanese patients diagnosed with primary IgAN: 10 patients who underwent tonsillectomy and corticosteroid therapy (T-CST), 7 who received corticosteroid therapy (CST), 8 who received conservative therapy (CO), and 5 with other renal diseases who received corticosteroid therapy (ORD) as disease controls. IgA was purified from patient sera collected at diagnosis and post-treatment. After sample preparation, O-glycoforms of the hinge region (HR) and N-glycoforms of the fragment crystallizable region were analyzed using high-resolution mass spectrometry (MS). RESULTS: The MS analysis of O-glycoforms of IgA1 showed that the relative abundance of IgA1 with 3GalNAc3Gal, which we previously identified as a characteristic IgA1 O-glycoform in IgAN, decreased post-treatment only in the T-CST group (P = 0.0195). Regarding N-glycoforms, the relative abundance of fucosylated N-glycan at asparagine (Asn)340 increased in the IgAN group compared with that in the ORD group (P = 0.0189) and decreased post-treatment only in the T-CST group (P = 0.0195). CONCLUSION: The MS analysis of O- and N-glycoforms of IgA1 revealed substantial changes in their abundance in the T-CST group but not in the CST, CO, and ORD groups. Our study provides new insights into how specific treatments alter the IgA1 glycoform abundance.
  • Masanori Nakanishi, Tomohiro Mizuno, Shinya Sakai, Daiki Hira, Takenao Koseki, Takeshi Matsubara, Hideki Yokoi, Motoko Yanagita, Tomohiro Terada, Shigeki Yamada, Naotake Tsuboi
    Clinical Drug Investigation 2025年3月13日  
  • Toshiyuki Narimiya, Hiroki Hayashi, Soshiro Ogata, Shigeo Hara, Akinao Okamoto, Kazuo Takahashi, Shigehisa Koide, Daijo Inaguma, Midori Hasegawa, Akihiro Tomita, Yukio Yuzawa, Naotake Tsuboi
    Clinical and experimental nephrology 29(3) 259-268 2025年3月  
    INTRODUCTION: Clinical epidemiological data on monoclonal gammopathy of renal significance (MGRS) are lacking. In this retrospective observational study, MGRS was compared with B-cell or plasma cell malignancies (BCM/PCM) with renal involvement to clarify differences in their clinical features. METHODS: Among the 1408 renal biopsies performed at our hospital, 25 MGRS and 18 BCM/PCM patients were identified. We investigated baseline characteristics and hematologic parameters of MGRS in reference to BCM/PCM using multivariable analysis. Cox proportional hazards analysis was performed for end-stage kidney disease (ESKD) and all-cause mortality. RESULTS: Comparing the MGRS with the BCM/PCM, mean differences in creatinine level, estimated glomerular filtration rate, and clonal bone marrow plasma cell percentage were - 2.76 mg/dL, 27.72 mL/min/1.73 m2, and - 18.86%, respectively (all P < 0.001). MGRS group had a predominance of glomerular lesions such as immunoglobulin-associated amyloidosis, cryoglobulinemic GN, and MIDD, and a lower risk of acute kidney injury/acute renal disease compared to BCM/PCM. During a median observation period of 23.7 months, clone-directed therapy was performed in 32.0% of patients in the MGRS group, compared to 83.3% of patients in the BCM/PCM group. Compared with BCM/PCM, MGRS had a hazard ratio of 0.66 (95% confidence interval (CI) 0.23-1.92, P = 0.45) for ESKD and 0.33 (95% CI 0.11-1.03, P = 0.06) for death in multivariate logistic regression analysis. CONCLUSIONS: The clinical characteristics of MGRS and BCM/PCM with monoclonal immunoglobulin-associated renal disease are disparate. Understanding these differences is crucial for developing tailored clinical approaches and therapeutic strategies to improve patient outcome.
  • Yasuhiro Katsumata, Ken-Ei Sada, Tomohiro Kameda, Hiroaki Dobashi, Shinya Kaname, Naotake Tsuboi, Yoshinori Matsumoto, Koichi Amano, Naoto Tamura, Masayoshi Harigai
    Immunological medicine 48(1) 47-57 2025年3月  
    We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.
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MISC

 166
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書籍等出版物

 23
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講演・口頭発表等

 12
  • 伊藤 辰将, 辰川 英樹, 梅田 良祐, 横江 優貴, 高橋 和男, 湯澤 由紀夫, 人見 清隆, 坪井 直毅
    日本腎臓学会誌 2021年6月 (一社)日本腎臓学会
  • 坪井 直毅, 横江 優貴, 北川 章充, 伊藤 辰将, 遠藤 信英, 丸山 彰一
    腎臓内科 2021年6月 (有)科学評論社
  • 細江 眞生, 森 万佑子, 鈴木 むつみ, 山田 幸恵, 新 典雄, 加藤 政雄, 大高 洋平, 長谷川 みどり, 坪井 直毅, 中井 滋
    日本透析医学会雑誌 2021年5月 (一社)日本透析医学会
  • 吉田 浩之, 湯澤 由紀夫, 長谷川 みどり, 稲熊 大城, 坪井 直毅, 林 宏樹, 小出 滋久, 大山 翔也, 多賀谷 知輝, 伊藤 辰将, 成宮 利幸, 磯貝 理恵子, 古田 弘貴, 堀内 雅人
    腎と透析 2020年8月 (株)東京医学社
  • Yuki Yokoe, Naotake Tsuboi, Takahiro Imaizumi, Akimitsu Kitagawa, Munetoshi Karasawa, Takaya Ozeki, Nobuhide Endo, Yuriko Sawa, Sawako Kato, Takayuki Katsuno, Shoichi Maruyama, Kunihiro Yamagata, Joichi Usui, Michio Nagata, Ken-Ei Sada, Hitoshi Sugiyama, Koichi Amano, Yoshihiro Arimura, Tatsuya Atsumi, Yukio Yuzawa, Hiroaki Dobashi, Yoshinari Takasaki, Masayoshi Harigai, Hitoshi Hasegawa, Hirofumi Makino, Seiichi Matsuo
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2020年7月8日
    BACKGROUND: The detection of leukocyte-derived CD11b (α subunit of integrin Mac-1) and CD163 (scavenger receptor) in urine may reflect renal inflammation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). The objective of this study was to evaluate the clinical significance of urinary CD11b (U-CD11b) and CD163 (U-CD163) in ANCA-GN. METHODS: U-CD11b and U-CD163 were examined using enzyme-linked immunosorbent assay in ANCA-GN urine samples from our institutional cohort (n = 88) and a nationwide cohort (n = 138), and their association with renal histology was subsequently analyzed. Logistic regression analyses were performed on a nationwide ANCA cohort to determine the associations of the two urinary molecules with renal remission failure at 6 months or with yearly estimated glomerular filtration rate (eGFR) slope over a 24-month observation period. RESULTS: U-CD11b and U-CD163 were significantly associated with cellular crescent formation and leukocyte accumulation in glomerular crescents. With regard to interstitial inflammation, both levels of U-CD11b and U-CD163 at diagnosis remarkably increased in ANCA-GN compared with the levels observed in nonglomerular kidney disorders including nephrosclerosis, immunoglobulin G4-related disease and tubulointerstitial nephritis; however, the presence of U-CD11b alone was significantly correlated with tubulointerstitial leukocyte infiltrates. Although neither U-CD11b nor U-CD163 at diagnosis was associated with remission failure at 6 months, multivariate analysis demonstrated that the baseline U-CD11b levels were significantly associated with the increase in eGFR following immunosuppressive therapy. CONCLUSIONS: Although both U-CD11b and U-CD163 reflect renal leukocyte accumulation, U-CD11b at diagnosis provides additional clinical value by predicting the recovery rate after the treatment of ANCA-GN.
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担当経験のある科目(授業)

 2

所属学協会

 5

共同研究・競争的資金等の研究課題

 18
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