Details of the Researcher

PHOTO

Sawako Goto
Section
Institute of Medical Research
Job title
Senior Assistant Professor
Degree

Research History 6

  • 2024/04 - Present
    東北大学病院　腎臓内科学分野/腎臓・高血圧内科　助教

  • 2019/04 - 2024/03
    Niigata University　Graduate School of Medical and Dental Sciences

  • 2015/04 - 2019/03
    Niigata University　Graduate School of Medical and Dental Sciences

  • 2014/04 - 2015/03
    Jichi Medical University

  • 2013/04 - 2014/03
    日本海総合病院　循環器内科・腎臓膠原病内科　後期研修医

  • 2011/04 - 2013/03
    山形県立中央病院　初期研修医

Show all Show first 5

Education 3

  • Niigata University　Graduate School of Medical and Dental Sciences　Course of Biological Functions and Medical Control

    2014/04 - 2019/03

  • Niigata University　Faculty of Medicine　School of Medicine

    2005/04 - 2011/03

  • 山形県立山形東高等学校

    2002/04 - 2005/03

Professional Memberships 5

  • JAPANESE SOCIETY FOR BIOMEDICAL MASS SPECTROMETRY

  • JAPAN COLLEGE OF RHEUMATOLOGY

  • THE JAPANESE SOCIETY FOR DIALYSIS THERAPY

  • JAPANESE SOCIETY OF NEPHROLOGY

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

Research Interests 6

  • 糖尿病性腎臓病

  • 慢性腎臓病

  • 急性腎障害

  • 質量分析

  • メガリン

  • 近位尿細管

Research Areas 1

  • Life sciences / Nephrology /

Papers 48

  1. Dapagliflozin ameliorates high-fat diet–induced, megalin-mediated autolysosomal dysfunction in proximal tubules via suppression of megalin-dependent endocytosis

    Kazuya Takemoto, Michihiro Hosojima, Hideyuki Kabasawa, Koichi Komochi, Hiroyuki Aoki, Nanako Sugita, Sawako Goto, Ryohei Kaseda, Satoru Nagatoishi, Kouhei Tsumoto, Ichiei Narita, Suguru Yamamoto, Akihiko Saito

    American Journal of Physiology-Renal Physiology　330　(6)　F712-F723　2026/06/01

    Publisher: American Physiological Society

    DOI： 10.1152/ajprenal.00448.2025 　

    ISSN： 1931-857X

    eISSN： 1522-1466

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    Here, megalin was found to mediate both receptor-mediated and fluid-phase endocytosis in vivo. Dapagliflozin ameliorates high-fat diet–induced autolysosomal dysfunction—particularly in segment 2 of proximal tubules—likely by suppressing megalin-dependent endocytosis without altering megalin expression levels. This suppression reduces metabolic overload in proximal tubules, supporting a renoprotective role for dapagliflozin in chronic kidney disease. These findings highlight a novel mechanism by which dapagliflozin might protect against tubular injury in the context of metabolic stress.

  2. Megalin-Mediated Direct and Indirect Pathways for the Development of Contrast-Induced Proximal Tubule Epithelial Cell Injury. International-journal

    Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Kazuya Takemoto, Hiroyuki Aoki, Koichi Komochi, Ryota Kobayashi, Nanako Sugita, Taeko Endo, Shoji Kuwahara, Takahiro Tanaka, Ryohei Kaseda, Satoru Nagatoishi, Yutaka Yoshida, Ichiei Narita, Suguru Yamamoto, Kouhei Tsumoto, Yoshiaki Hirayama, Akihiko Saito

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology　39　(20)　e71136　2025/10/31

    DOI： 10.1096/fj.202500985R 　

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    Megalin is a multiligand endocytic receptor in proximal tubule epithelial cells (PTECs) that facilitates the reabsorption of certain nephrotoxic drugs. Notably, cilastatin competes with these drugs for binding to megalin. Patients with chronic kidney disease are at increased risk of contrast-induced (CI) acute kidney injury, in which iodine-mediated PTEC toxicity is a crucial pathogenic factor. This study investigated the interplay between megalin and CI-PTEC injury, along with the protective effect of cilastatin, utilizing electron probe microanalysis, a mouse CI-PTEC injury model, quartz crystal microbalance analysis, and binding assays with magnetic beads immobilized with iomeprol, a water-soluble nonionic contrast medium (CM). Electron probe microanalysis revealed the reduced renal uptake of CMs in the kidney cortex of kidney-specific conditional megalin-knockout mice compared with controls. In the CI-PTEC injury model using kidney-specific conditional or mosaic megalin-knockout mice, a significant reduction of vacuolization was observed in PTECs in the cortex compared with controls in the former, while co-expression of megalin and kidney injury molecule-1 was observed in the latter. These findings indicate that megalin is involved in the development of CI-PTEC injury. Cilastatin inhibited the renal uptake of CMs and ameliorated CI-PTEC injury in wild-type mice. Of note, two distinct pathways of renal CM uptake were delineated, both of which cilastatin inhibited: the direct binding of CMs to megalin and an indirect route involving transcobalamin-2, an endocytic megalin ligand, functioning as a CM carrier. Collectively, megalin governs the direct and indirect pathways in the development of CI-PTEC injury, and cilastatin effectively impedes both.

  3. Development of sandwich enzyme-linked immunosorbent assays quantifying mouse urinary megalin, a novel proximal tubular biomarker. International-journal

    Rina Sofuku, Sayaka Miyazaki, Michihiro Hosojima, Sawako Goto, Kazuya Takemoto, Hideyuki Kabasawa, Taeko Endo, Koichi Komochi, Nanako Sugita, Hiroyuki Aoki, Ryota Kobayashi, Ichiei Narita, Akihiko Saito

    Journal of immunological methods　534　113763-113763　2024/11

    DOI： 10.1016/j.jim.2024.113763 　

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    Megalin, a type I transmembrane protein, serves as a multi-ligand endocytic receptor in the apical membrane of proximal tubules. Its ectodomain and full-length forms are excreted into human urine, with the former being more abundant. We previously developed two types of sandwich enzyme-linked immunosorbent assays (ELISAs) utilizing monoclonal antibodies that target the amino-terminal ligand-binding domain-I and the carboxyl-terminal cytoplasmic region of human megalin, respectively. The former, termed "A-megalin" ELISA, primarily identifies ectodomains of megalin, whereas the latter, "C-megalin" ELISA, specifically recognizes full-length megalin originating from urinary extracellular vesicles. This study developed novel sandwich ELISAs to assess mouse urinary A-megalin and C-megalin, thereby facilitating studies involving these biomarkers in mouse disease models. Immunoblotting and immunohistochemistry of monoclonal antibodies against human megalin were performed to assess their compatibility with mouse megalin in novel sandwich ELISAs, which were constructed and validated using human assay protocols. Immunoblot analysis of megalin in urinary extracellular vesicles and supernatant was performed to investigate the ratio of ectodomain to full-length forms in mouse urine. Stable measurements having a precision and accuracy within 15 % were achieved in the measurement of quality control samples. A-megalin and C-megalin were detectable in the urine of C57BL/6 mice, whereas most urine samples from kidney-specific conditional megalin-knockout mice were below detection limits. Ectodomain forms of megalin were at least approximately 70 times more abundant than the full-length form, even in mouse urine. In conclusion, we successfully developed sandwich ELISAs for assessing mouse urinary A-megalin and C-megalin to evaluate primarily ectodomain and full-length forms of megalin, respectively.

  4. マルチビタミンの長期過剰摂取による高Ca血症の遷延と二次性シュウ酸腎症を認めた一例

    入沢 大喜, 逸見 太郎, 後藤 佐和子, 蒲澤 秀門, 細島 康宏, 伊藤 由美, 今井 直史, 山本 卓, 後藤 眞, 成田 一衛

    日本腎臓学会誌　66　(6-E)　889-889　2024/09

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  5. メガリン機能抑制を介したSGLT2阻害薬による腎保護機序

    竹本 和矢, 細島 康宏, 後藤 佐和子, 蒲澤 秀門, 杉田 奈々子, 遠藤 多恵子, 青木 弘行, 小餅 耕一, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　66　(4)　581-581　2024/06

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  6. Cryo-EM structures elucidate the multiligand receptor nature of megalin. International-journal

    Sawako Goto, Akihisa Tsutsumi, Yongchan Lee, Michihiro Hosojima, Hideyuki Kabasawa, Koichi Komochi, Satoru Nagatoishi, Kazuya Takemoto, Kouhei Tsumoto, Tomohiro Nishizawa, Masahide Kikkawa, Akihiko Saito

    Proceedings of the National Academy of Sciences of the United States of America　121　(22)　e2318859121　2024/05/28

    DOI： 10.1073/pnas.2318859121 　

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    Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157, 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori et al., J. Am. Soc. Nephrol. 28, 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic et al., Proc. Natl. Acad. Sci. U.S.A. 93, 4229-4234 (1996)], and other illnesses.

  7. Megalin-related mechanism of hemolysis-induced acute kidney injury and the therapeutic strategy. International-journal

    Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Kaho Arai, Kazuya Takemoto, Hiroyuki Aoki, Koichi Komochi, Ryota Kobayashi, Nanako Sugita, Taeko Endo, Ryohei Kaseda, Yutaka Yoshida, Ichiei Narita, Yoshiaki Hirayama, Akihiko Saito

    The Journal of pathology　2024/05/09

    DOI： 10.1002/path.6284 　

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    Hemolysis-induced acute kidney injury (AKI) is attributed to heme-mediated proximal tubule epithelial cell (PTEC) injury and tubular cast formation due to intratubular protein condensation. Megalin is a multiligand endocytic receptor for proteins, peptides, and drugs in PTECs and mediates the uptake of free hemoglobin and the heme-scavenging protein α1-microglobulin. However, understanding of how megalin is involved in the development of hemolysis-induced AKI remains elusive. Here, we investigated the megalin-related pathogenesis of hemolysis-induced AKI and a therapeutic strategy using cilastatin, a megalin blocker. A phenylhydrazine-induced hemolysis model developed in kidney-specific mosaic megalin knockout (MegKO) mice confirmed megalin-dependent PTEC injury revealed by the co-expression of kidney injury molecule-1 (KIM-1). In the hemolysis model in kidney-specific conditional MegKO mice, the uptake of hemoglobin and α1-microglobulin as well as KIM-1 expression in PTECs was suppressed, but tubular cast formation was augmented, likely due to the nonselective inhibition of protein reabsorption in PTECs. Quartz crystal microbalance analysis revealed that cilastatin suppressed the binding of megalin with hemoglobin and α1-microglobulin. Cilastatin also inhibited the specific uptake of fluorescent hemoglobin by megalin-expressing rat yolk sac tumor-derived L2 cells. In a mouse model of hemolysis-induced AKI, repeated cilastatin administration suppressed PTEC injury by inhibiting the uptake of hemoglobin and α1-microglobulin and also prevented cast formation. Hemopexin, another heme-scavenging protein, was also found to be a novel ligand of megalin, and its binding to megalin and uptake by PTECs in the hemolysis model were suppressed by cilastatin. Mass spectrometry-based semiquantitative analysis of urinary proteins in cilastatin-treated C57BL/6J mice indicated that cilastatin suppressed the reabsorption of a limited number of megalin ligands in PTECs, including α1-microglobulin and hemopexin. Collectively, cilastatin-mediated selective megalin blockade is an effective therapeutic strategy to prevent both heme-mediated PTEC injury and cast formation in hemolysis-induced AKI. © 2024 The Pathological Society of Great Britain and Ireland.

  8. The structure of the rat vitamin B12 transporter TC and its complex with glutathionylcobalamin. International-journal

    Marcel Bokhove, Takashi Kawamura, Hideo Okumura, Sawako Goto, Yoshiaki Kawano, Stefan Werner, Franziska Jarczowski, Victor Klimyuk, Akihiko Saito, Takashi Kumasaka

    The Journal of biological chemistry　300　(5)　107289-107289　2024/05

    DOI： 10.1016/j.jbc.2024.107289 　

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    Vitamin B12 (cobalamin or Cbl) functions as a cofactor in two important enzymatic processes in human cells, and life is not sustainable without it. B12 is obtained from food and travels from the stomach, through the intestine, and into the bloodstream by three B12-transporting proteins: salivary haptocorrin (HC), gastric intrinsic factor, and transcobalamin (TC), which all bind B12 with high affinity and require proteolytic degradation to liberate Cbl. After intracellular delivery of dietary B12, Cbl in the aquo/hydroxocobalamin form can coordinate various nucleophiles, for example, GSH, giving rise to glutathionylcobalamin (GSCbl), a naturally occurring form of vitamin B12. Currently, there is no data showing whether GSCbl is recognized and transported in the human body. Our crystallographic data shows for the first time the complex between a vitamin B12 transporter and GSCbl, which compared to aquo/hydroxocobalamin, binds TC equally well. Furthermore, sequence analysis and structural comparisons show that TC recognizes and transports GSCbl and that the residues involved are conserved among TCs from different organisms. Interestingly, haptocorrin and intrinsic factor are not structurally tailored to bind GSCbl. This study provides new insights into the interactions between TC and Cbl.

  9. Defective C3d caused by C3 p.<scp>W1034R</scp> in inherited atypical hemolytic uremic syndrome

    Masafumi Tsuchida, Shin Goto, Hirofumi Watanabe, Sawako Goto, Hiroki Yamaguchi, Ichiei Narita

    Molecular Genetics &amp; Genomic Medicine　2023/10/05

    Publisher: Wiley

    DOI： 10.1002/mgg3.2288 　

    ISSN： 2324-9269

    eISSN： 2324-9269

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    Abstract Introduction Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy. Personal genome analyses have revealed numerous aHUS‐causing variants, mainly complement‐related genes. However, not all aHUS‐causing variants have been functionally validated. Methods An exome sequence analysis of a Japanese multiplex family composed of three patients diagnosed with aHUS in infancy and showing frequent relapses clustered in a dominant transmission mode was performed. Protein interaction between the C3d and C‐terminal domains of factor H was analyzed using a quartz crystal microbalance. Results Following filtering by heterozygous variants, amino acid substitutions, and allele frequency, the analysis revealed eight rare variants shared by the affected individuals. Variant prioritization listed C3 p.W1034R as the most likely candidate gene mutation in the affected individuals, despite being classified as a variant of uncertain significance. Binding of recombinant C3d harboring 1034R to recombinant short consensus repeats 15 to 20 of factor H was significantly suppressed compared with that of C3 with 1034W. Conclusion C3 p.W1034R results in an inherited form of aHUS that often presents with recurrent episodes, possibly because of impaired interactions between the C3d and C‐terminal domains of factor H. Following comprehensive genomic analysis, functional validation of C3 p.W1034R strengthens the molecular basis for aHUS pathophysiology.

  10. Megalin is involved in angiotensinogen-induced, angiotensin II-mediated ERK1/2 signaling to activate Na+-H+ exchanger 3 in proximal tubules. International-journal Peer-reviewed

    Sawako Goto, Yutaka Yoshida, Michihiro Hosojima, Shoji Kuwahara, Hideyuki Kabasawa, Hiroyuki Aoki, Tomomichi Iida, Ryuhei Sawada, Daisuke Ugamura, Yuta Yoshizawa, Kazuya Takemoto, Koichi Komochi, Ryota Kobayashi, Ryohei Kaseda, Eishin Yaoita, Satoru Nagatoishi, Ichiei Narita, Kouhei Tsumoto, Akihiko Saito

    Journal of hypertension　2023/09/08

    DOI： 10.1097/HJH.0000000000003555 　

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    BACKGROUND: Kidney angiotensin (Ang) II is produced mainly from liver-derived, glomerular-filtered angiotensinogen (AGT). Podocyte injury has been reported to increase the kidney Ang II content and induce Na+ retention depending on the function of megalin, a proximal tubular endocytosis receptor. However, how megalin regulates the renal content and action of Ang II remains elusive. METHODS: We used a mass spectrometry-based, parallel reaction-monitoring assay to quantitate Ang II in plasma, urine, and kidney homogenate of kidney-specific conditional megalin knockout (MegKO) and control (Ctl) mice. We also evaluated the pathophysiological changes in both mouse genotypes under the basal condition and under the condition of increased glomerular filtration of AGT induced by administration of recombinant mouse AGT (rec-mAGT). RESULTS: Under the basal condition, plasma and kidney Ang II levels were comparable in the two mouse groups. Ang II was detected abundantly in fresh spot urine in conditional MegKO mice. Megalin was also found to mediate the uptake of intravenously administered fluorescent Ang II by PTECs. Administration of rec-mAGT increased kidney Ang II, exerted renal extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, activated proximal tubular Na+-H+ exchanger 3 (NHE3), and decreased urinary Na+ excretion in Ctl mice, whereas these changes were suppressed but urinary Ang II was increased in conditional MegKO mice. CONCLUSION: Increased glomerular filtration of AGT is likely to augment Ang II production in the proximal tubular lumen. Thus, megalin-dependent Ang II uptake should be involved in the ERK1/2 signaling that activates proximal tubular NHE3 in vivo, thereby causing Na+ retention.

  11. 【尿細管機能異常の臨床】腎障害における尿細管 慢性腎臓病と尿細管機能

    細島 康宏, 蒲澤 秀門, 後藤 佐和子, 斎藤 亮彦

    腎臓内科　17　(5)　505-512　2023/05

    Publisher: (有)科学評論社

    ISSN： 2435-1903

  12. メガリンが関与する造影剤腎症の発症メカニズムの解明とその予防法の開発

    後藤 佐和子, 細島 康宏, 蒲澤 秀門, 忰田 亮平, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　65　(3)　248-248　2023/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  13. シスプラチンを含むがん化学療法におけるシラスタチンの急性腎障害予防効果を検討するための薬物動態試験

    蒲澤 秀門, 細島 康宏, 後藤 佐和子, 田中 崇裕, 北村 信隆, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　65　(3)　274-274　2023/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  14. SGLT2阻害薬使用時におけるメガリンおよびメガリンリガンドの尿中排泄量の推移

    細島 康宏, 蒲澤 秀門, 田中 崇裕, 北村 信隆, 後藤 佐和子, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　65　(3)　319-319　2023/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  15. 透析患者の甲状腺乳頭癌に対し,放射性ヨウ素内用療法を実施した経験例

    渡邉 和樹, 後藤 佐和子, 渡辺 博文, 細島 康宏, 野林 大幹, 飯田 倫理, 青柳 竜治, 海津 元樹, 山本 卓, 成田 一衛

    日本透析医学会雑誌　56　(Suppl.1)　540-540　2023/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  16. 透析患者の甲状腺乳頭癌に対し,放射性ヨウ素内用療法を実施した経験例

    渡邉 和樹, 後藤 佐和子, 渡辺 博文, 細島 康宏, 野林 大幹, 飯田 倫理, 青柳 竜治, 海津 元樹, 山本 卓, 成田 一衛

    日本透析医学会雑誌　56　(Suppl.1)　540-540　2023/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  17. SGLT2阻害薬使用時における尿中メガリンおよびメガリンリガンド分子の動態

    細島 康宏, 蒲澤 秀門, 田中 崇裕, 北村 信隆, 後藤 佐和子, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    糖尿病　66　(Suppl.1)　S-286　2023/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  18. The endocytosis receptor megalin: From bench to bedside. International-journal

    Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Akihiko Saito

    The international journal of biochemistry & cell biology　157　106393-106393　2023/04

    DOI： 10.1016/j.biocel.2023.106393 　

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    The large (∼600 kDa) endocytosis receptor megalin/low-density lipoprotein receptor-related protein 2 is highly expressed at the apical membrane of proximal tubular epithelial cells (PTECs). Megalin plays an important role in the endocytosis of various ligands via interactions with intracellular adaptor proteins, which mediate the trafficking of megalin in PTECs. Megalin mediates the retrieval of essential substances, including carrier-bound vitamins and elements, and impairment of the endocytic process may result in the loss of those substances. In addition, megalin reabsorbs nephrotoxic substances such as antimicrobial (colistin, vancomycin, and gentamicin) or anticancer (cisplatin) drugs and advanced glycation end product-modified or fatty acid-containing albumin. The megalin-mediated uptake of these nephrotoxic ligands causes metabolic overload in PTECs and leads to kidney injury. Blockade or suppression of the megalin-mediated endocytosis of nephrotoxic substances may represent a novel therapeutic strategy for drug-induced nephrotoxicity or metabolic kidney disease. Megalin reabsorbs urinary biomarker proteins such as albumin, α1-microglobulin, β2-microglobulin, and liver-type fatty acid-binding protein; thus, the above-mentioned megalin-targeted therapy may have an effect on the urinary excretion of these biomarkers. We have previously established a sandwich enzyme-linked immunosorbent assay to measure the ectodomain (A-megalin) and full-length (C-megalin) forms of urinary megalin using monoclonal antibodies against the amino- and carboxyl-terminals of megalin, respectively, and reported their clinical usefulness. In addition, there have been reports of patients with novel pathological anti-brush border autoantibodies targeting megalin in the kidney. Even with these breakthroughs in the characterization of megalin, a large number of issues remain to be addressed in future research.

  19. Rothmund-Thomson症候群に合併した特発性多中心性Castleman病(iMCD)の1例

    米沢 正貴, 後藤 佐和子, 後藤 慧, 蒲澤 秀門, 細島 康宏, 今井 直史, 伊藤 由美, 成田 一衛, 正木 康史

    日本腎臓学会誌　64　(6-E)　584-584　2022/10

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  20. Urinary A- and C-megalin predict progression of diabetic kidney disease: an exploratory retrospective cohort study. International-journal

    Tomomichi Iida, Michihiro Hosojima, Hideyuki Kabasawa, Keiko Yamamoto-Kabasawa, Sawako Goto, Takahiro Tanaka, Nobutaka Kitamura, Mitsutaka Nakada, Shino Itoh, Shinya Ogasawara, Ryohei Kaseda, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

    Journal of diabetes and its complications　36　(11)　108312-108312　2022/09/24

    DOI： 10.1016/j.jdiacomp.2022.108312 　

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    AIMS: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD). METHODS: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin. RESULTS: We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were - 0.904 and -0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was -1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase). CONCLUSIONS: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

  21. 2型糖尿病患者における尿中メガリン測定による腎予後予測

    飯田 倫理, 細島 康宏, 蒲澤 秀門, 蒲澤 佳子, 後藤 佐和子, 田中 崇裕, 北村 信隆, 忰田 亮平, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　64　(3)　240-240　2022/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  22. 2型糖尿病患者における尿中メガリンの腎予後予測能の検討

    飯田 倫理, 細島 康宏, 蒲澤 秀門, 蒲澤 佳子, 後藤 佐和子, 田中 崇裕, 北村 信隆, 忰田 亮平, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    糖尿病　65　(Suppl.1)　S-150　2022/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  23. Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury. International-journal

    Ryo Kawakami, Miki Matsui, Ayumu Konno, Ryosuke Kaneko, Shreya Shrestha, Suman Shrestha, Hiroaki Sunaga, Hirofumi Hanaoka, Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Masaru Obokata, Norimichi Koitabashi, Hiroki Matsui, Tsutomu Sasaki, Akihiko Saito, Motoko Yanagita, Hirokazu Hirai, Masahiko Kurabayashi, Tatsuya Iso

    The Journal of pathology　255　(4)　362-373　2021/08/09

    DOI： 10.1002/path.5775 　

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    Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte- or in a PTEC-specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

  24. 糸球体結節性病変と係蹄壁へのIgG線状沈着を呈した境界型糖尿病の1例

    山口 浩毅, 細島 康宏, 蒲澤 秀門, 後藤 佐和子, 後藤 慧, 伊藤 由美, 今井 直史, 金子 佳賢, 鈴木 芳樹, 齋藤 亮彦, 成田 一衛

    糖尿病　64　(7)　411-411　2021/07

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  25. 糸球体結節性病変と係蹄壁へのIgG線状沈着を呈した境界型糖尿病の1例

    山口 浩毅, 細島 康宏, 蒲澤 秀門, 後藤 佐和子, 後藤 慧, 伊藤 由美, 今井 直史, 金子 佳賢, 鈴木 芳樹, 齋藤 亮彦, 成田 一衛

    糖尿病　64　(7)　411-411　2021/07

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  26. 腎尿細管上皮細胞における二重の脂肪酸取り込み機構の同定

    川上 亮, 花岡 宏史, 金井 彩香, 大日方 英, 中野 大介, 松崎 利行, 後藤 佐和子, 斉藤 亮彦, 西山 成, 柳田 素子, 倉林 正彦, 磯 達也

    血管　44　(1)　43-43　2021/06

    Publisher: 日本心脈管作動物質学会

    ISSN： 0911-4637

  27. 小児尿中メガリン基準値の設定

    金子 昌弘, 山田 剛史, 後藤 佐和子, 蒲澤 秀門, 細島 康宏, 斎藤 亮彦

    日本小児腎臓病学会雑誌　34　(1Suppl.)　136-136　2021/05

    Publisher: (一社)日本小児腎臓病学会

    ISSN： 0915-2245

    eISSN： 1881-3933

  28. 小児尿中メガリン基準値の設定

    金子 昌弘, 山田 剛史, 後藤 佐和子, 蒲澤 秀門, 細島 康宏, 斎藤 亮彦

    日本小児腎臓病学会雑誌　34　(1Suppl.)　136-136　2021/05

    Publisher: (一社)日本小児腎臓病学会

    ISSN： 0915-2245

    eISSN： 1881-3933

  29. Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity. International-journal

    Masashi Arita, Satoshi Watanabe, Nobumasa Aoki, Shoji Kuwahara, Ryo Suzuki, Sawako Goto, Yuko Abe, Miho Takahashi, Miyuki Sato, Satoshi Hokari, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Masachika Hayashi, Yasuyoshi Ohshima, Hideyuki Kabasawa, Michihiro Hosojima, Toshiyuki Koya, Akihiko Saito, Toshiaki Kikuchi

    Scientific reports　11　(1)　750-750　2021/01/12

    DOI： 10.1038/s41598-020-80853-6 　

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    Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

  30. マウス尿中メガリン測定用サンドイッチELISAの開発とその応用

    早福 莉那, 後藤 佐和子, 細島 康宏, 蒲澤 秀門, 忰田 亮平, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　62　(4)　339-339　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  31. メガリンを介する腎内レニン-アンジオテンシン(Ang)系(RAS)の動的均衡化制御機構

    後藤 佐和子, 吉田 豊, 細島 康宏, 蒲澤 秀門, 忰田 亮平, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　62　(4)　370-370　2020/07

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  32. SGLT2阻害薬による腎保護作用機序と尿中コンパニオン診断法の検討

    忰田 亮平, 飯田 倫理, 細島 康宏, 蒲澤 秀門, 後藤 佐和子, 桑原 頌治, 宇賀村 大亮, 吉澤 優太, 田中 崇裕, 成田 一衛, 斎藤 亮彦

    臨床薬理の進歩　(41)　148-153　2020/06

    Publisher: (公財)臨床薬理研究振興財団

    ISSN： 0914-4366

    More details Close

    軽度〜中等度腎機能障害を有する成人2型糖尿病患者(残存機能ネフロンに過剰代謝負荷がかかっていることが推測される)を対象に、エンパグリフロジンによる腎機能保護作用を検証するとともに尿中メガリン(およびメガリンリガンド分子)の動態を調べ、腎機能保護作用がメガリン機能に関連したものであるか検討した。さらに、尿中メガリンなどの検査がコンパニオン診断として有用であるか、探索的な検討を行った。また、SGLT2阻害薬がメガリンの発現・機能に及ぼす影響についても検討を継続した。臨床試験の被験者51名で、平均年齢は62歳であり、男性が32名であった。2名が有害反応のため脱落したが、6ヵ月後、HbA1cとBMIが減少した。現在、メガリンを含む尿中バイオマーカーの推移について解析を行っている。ダパグリフロジン、エンパグリフロジンを投与されたマウスでは尿中の糖排泄増加を認めたが血糖値に差は認められなかった。免疫組織化学染色では近位尿細管におけるメガリンの染色性が低下していることが確認された。またウエスタンブロット法において、メガリンの蛋白がvehicle群と比較して低下していることが認められた。リアルタイムRT-PCRにおいてもメガリンmRNAがvehicle群と比較して低下していることが確認された。ダパグリフロジンを添加されたIRPTCではメガリン蛋白の低下が認められ、mRNAの低下も認められた。

  33. Low bone mineral density due to secondary hyperparathyroidism in the GlatmTg(CAG-A4GALT) mouse model of Fabry disease. International-journal

    Hiroki Maruyama, Atsumi Taguchi, Mariko Mikame, Hongmei Lu, Norihiro Tada, Muneaki Ishijima, Haruka Kaneko, Mariko Kawai, Sawako Goto, Akihiko Saito, Riuko Ohashi, Yuji Nishikawa, Satoshi Ishii

    FASEB bioAdvances　2　(6)　365-381　2020/06

    DOI： 10.1096/fba.2019-00080 　

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    Low bone mineral density (BMD)-diagnosed as osteoporosis or osteopenia-has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [GlatmTg(CAG-A4GALT)] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca2+ reabsorption and hypercalciuria. Here, we investigated bone metabolism in GlatmTg(CAG-A4GALT) mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age via micro-X-ray-computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca2+-not plasma fibroblast growth factor 23 (FGF-23) elevation-by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF-23 levels with phosphaturic action. The expression of 1α-hydroxylase [synthesis of 1α,25(OH)2D3] in the kidney did not decrease, but that of 24-hydroxylase [degradation of 1α,25(OH)2D3] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)2D3 and 25(OH)D3 levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice.

  34. Rice Endosperm Protein Administration to Juvenile Mice Regulates Gut Microbiota and Suppresses the Development of High-Fat Diet-Induced Obesity and Related Disorders in Adulthood. International-journal Peer-reviewed

    Higuchi Y, Hosojima M, Kabasawa H, Kuwahara S, Goto S, Toba K, Kaseda R, Tanaka T, Kitamura N, Takihara H, Okuda S, Taniguchi M, Arao H, Narita I, Saito A

    Nutrients　11　(12)　2019/12

    DOI： 10.3390/nu11122919 　

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    Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear. Therefore, we used a mouse model to experimentally investigate the preconditioning effects of REP intake during childhood on the development of obesity and related disorders in adulthood. Male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP during the juvenile period and then a high-fat diet (HFD) containing casein or REP during adulthood. Mice fed REP during the juvenile period showed better body weight, blood pressure, serum lipid profiles, lipopolysaccharide (LPS)-binding protein levels, and glucose tolerance in adulthood than those fed casein during the juvenile period. HFD-induced renal tubulo-glomerular alterations and hepatic microvesicular steatosis were less evident in REP-fed mice than in casein-fed ones. REP intake during the juvenile period improved HFD-induced dysbiosis (i.e., Escherichia genus proliferation and reduced gut microbiota diversity), thereby suppressing endotoxin-related chronic inflammation. Indeed, REP-derived peptides showed antibacterial activity against Escherichia coli, a major producer of LPS. In conclusion, REP supplementation during the juvenile period may regulate the gut microbiota and thus suppress the development of obesity and related disorders in adulthood in mice.

  35. 自己末梢血幹細胞移植後に血栓性微小血管症(TMA)による腎障害を合併した一例

    白柏 由佳, 後藤 佐和子, 細島 康宏, 保坂 聖子, 山本 卓, 今井 直史, 伊藤 由美, 後藤 眞, 成田 一衛

    日本腎臓学会誌　60　(6)　876-876　2018/08

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  36. SGLT2阻害薬ダパグリフロジンの腎近位尿細管細胞における血糖値非依存的なメガリン発現抑制作用

    飯田 倫理, 桑原 頌治, 細島 康宏, 石川 友美, 後藤 佐和子, 蒲澤 秀門, 忰田 亮平, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    糖尿病　61　(Suppl.1)　S-382　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  37. Bardoxolone methylによる腎近位尿細管のメガリン調節機構の検討

    吉澤 優太, 桑原 頌治, 細島 康宏, 蒲澤 秀門, 忰田 亮平, 宇賀村 大亮, 後藤 佐和子, 飯田 倫理, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    糖尿病　61　(Suppl.1)　S-383　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

    eISSN： 1881-588X

  38. Differences in the adsorption of nafamostat mesilate between polyester-polymer alloy and polysulfone membranes Peer-reviewed

    Sawako Goto, Susumu Ookawara, Akihiko Saito

    JOURNAL OF ARTIFICIAL ORGANS　20　(2)　138-144　2017/06

    DOI： 10.1007/s10047-016-0937-2 　

    ISSN： 1434-7229

    eISSN： 1619-0904

  39. Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity International-journal Peer-reviewed

    Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY　28　(6)　1783-1791　2017/06

    DOI： 10.1681/ASN.2016060606 　

    ISSN： 1046-6673

    eISSN： 1533-3450

  40. Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy International-journal Peer-reviewed

    Shankhajit De, Shoji Kuwahara, Michihiro Hosojima, Tomomi Ishikawa, Ryohei Kaseda, Piyali Sarkar, Yusuke Yoshioka, Hideyuki Kabasawa, Tomomichi Iida, Sawako Goto, Koji Toba, Yuki Higuchi, Yoshiki Suzuki, Masanori Hara, Hiroyuki Kurosawa, Ichiei Narita, Yoshiaki Hirayama, Takahiro Ochiya, Akihiko Saito

    DIABETES　66　(5)　1391-1404　2017/05

    DOI： 10.2337/db16-1031 　

    ISSN： 0012-1797

    eISSN： 1939-327X

  41. Effectiveness of Plasma Exchange for Acute Pancreatitis Induced by Hypertriglyceridemia During Pregnancy International-journal Peer-reviewed

    Sawako Goto, Susumu Ookawara, Kaoru Tabei

    THERAPEUTIC APHERESIS AND DIALYSIS　20　(1)　98-99　2016/01

    DOI： 10.1111/1744-9987.12373 　

    ISSN： 1744-9979

    eISSN： 1744-9987

  42. Case of rapidly progressive glomerulonephritis exhibiting granulomatosis with polyangiitis (GPA) and extremely high level of PR3-ANCA with improvement of renal dysfunction after plasma exchange therapy Peer-reviewed

    Mitsutoshi Shindo, Susumu Ookawara, Kiyonori Ito, Taisuke Kitano, Sawako Goto, Haruhisa Miyazawa, Yuichiro Ueda, Yoshio Kaku, Keiji Hirai, Taro Hoshino, Honami Mori, Izumi Yoshida, Kaoru Tabei, Yoshiyuki Morishita

    Japanese Journal of Nephrology　58　(4)　596-603　2016

    Publisher: Japanese Society of Nephrology

    ISSN： 0385-2385

  43. Effectiveness of plasma exchange for acquired type A hemophilia. Peer-reviewed

    Goto S, Ookawara S, Ueda Y, Ito K, Miyazawa H, Kitano T, Shindo M, Kaku Y, Hirai K, Hoshino T, Ashizawa M, Mori H, Yoshida I, Tabei K

    CEN case reports　4　(2)　196-199　2015/11

    DOI： 10.1007/s13730-015-0168-z 　

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    An 80-year-old man was treated at our hospital for chronic kidney disease, diabetes mellitus and hypertension. He presented a bleeding tendency over the past several weeks. When he was admitted to our hospital with a consciousness disturbance, he had irregular 10-20 cm patches of subcutaneous bleeding. Laboratory findings showed prolonged activated partial thromboplastin time (APTT) but normal platelet count and prothrombin time. The administration of fresh frozen plasma did not control the bleeding tendency and the result of APTT cross-mixing test suggested the presence of factor VIII inhibitor. The diagnosis of acquired hemophilia A was made by a marked decrease in factor VIII activity levels (<1 %) and a high titer of factor VIII inhibitor (11 Bethesda units). To remove the factor VIII inhibitor and suppress its production, plasma exchange was performed and methylprednisolone was administered. Thereafter, the bleeding tendency could be controlled with APTT measurement normalization. Plasma exchange does not have a first priority in the treatment but our case findings suggested that plasma exchange is an effective method for eliminating factor VIII inhibitor and alleviating acquired hemophilia A severity.

  44. Factors Affecting Cerebral Oxygenation in Hemodialysis Patients: Cerebral Oxygenation Associates with pH, Hemodialysis Duration, Serum Albumin Concentration, and Diabetes Mellitus International-journal Peer-reviewed

    Kiyonori Ito, Susumu Ookawara, Yuichiro Ueda, Sawako Goto, Haruhisa Miyazawa, Hodaka Yamada, Taisuke Kitano, Mitsunobu Shindo, Yoshio Kaku, Keiji Hirai, Masashi Yoshida, Taro Hoshino, Aoi Nabata, Honami Mori, Izumi Yoshida, Masafumi Kakei, Kaoru Tabei

    PLOS ONE　10　(2)　e0117474　2015/02

    DOI： 10.1371/journal.pone.0117474 　

    ISSN： 1932-6203

  45. Non-Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency that Developed into Symptomatic Severe Hyponatremia Peer-reviewed

    Sawako Goto, Susumu Ookawara, Kaoru Takase, Mizue Goto, Takahiro Nakayama, Yuhta Oyama, Kaoru Tabei

    INTERNAL MEDICINE　54　(10)　1273-1276　2015

    DOI： 10.2169/internalmedicine.54.3901 　

    ISSN： 0918-2918

    eISSN： 1349-7235

  46. A higher cardiothoracic ratio is associated with 2-year mortality after hemodialysis initiation Peer-reviewed

    Kiyonori Ito, Susumu Ookawara, Yuichiro Ueda, Haruhisa Miyazawa, Hodaka Yamada, Sawako Goto, Hiroki Ishii, Mitsutoshi Shindo, Taisuke Kitano, Keiji Hirai, Masashi Yoshida, Yoshio Kaku, Taro Hoshino, Aoi Nabata, Honami Mori, Izumi Yoshida, Masafumi Kakei, Yoshiyuki Morishita, Kaoru Tabei

    Nephron Extra　5　(3)　100-110　2015

    Publisher: S. Karger AG

    DOI： 10.1159/000442591 　

    ISSN： 1664-5529

  47. Superior mesenteric artery syndrome due to duodenal edema in a chronic renal failure patient: a case report. Peer-reviewed

    Goto S, Ookawara S, Sugai M

    CEN case reports　3　(1)　14-17　2014/05

    DOI： 10.1007/s13730-013-0076-z 　

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    A 74-year-old woman had been treated conservatively for type 2 diabetes mellitus (DM) and DM nephropathy since 2004. Her renal function gradually deteriorated, and she developed chronic renal failure (CRF) with a serum creatinine level between 2.5 and 3.0 mg/dl in 2010. She presented to our hospital with nausea and vomiting related to the progression of CRF in May 2011. An abdominal computed tomography (CT) scan showed distention of the upper digestive tract from the stomach to the third portion of the duodenum, ascites, and compression of the duodenum by the abdominal aortic artery and the overlying superior mesenteric artery (SMA), which was caused by edema along the gastrointestinal tract, in particular, at the duodenum. Therefore, she was diagnosed with SMA syndrome. Decompression of the distended upper digestive tract was achieved using a nasogastric tube, and hemodialysis was also initiated in order to adequately control her fluid balance disorder, which was thought to have induced the duodenal edema and ascites. After initiating these treatments, her condition gradually improved, and she fully recovered after approximately 2 months of treatment. Thus far, there has been no report of SMA syndrome caused by duodenal edema associated with the progression of CRF that was successfully treated by conservative treatment and the initiation of blood purification.

  48. Evaluation of Cerebral Oxygenation in Patients Undergoing Long-Term Hemodialysis International-journal Peer-reviewed

    Taro Hoshino, Susumu Ookawara, Sawako Goto, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Yoshio Kaku, Keiji Hirai, Aoi Nabata, Honami Mori, Izumi Yoshida, Kaoru Tabei

    NEPHRON CLINICAL PRACTICE　126　(1)　57-61　2014

    DOI： 10.1159/000358432 　

    ISSN： 1660-2110

Show all ︎Show first 5

Misc. 22

  1. 尿細管間質障害―最新の知見 抗メガリン/LRP2腎症

    蒲澤秀門, 細島康宏, 後藤佐和子, 斎藤亮彦

    腎と透析　87　(2)　356‐360-360　2019/08/25

    Publisher: (株)東京医学社

    ISSN： 0385-2156

  2. メガリンを介した抗癌化学療法による腎障害の対策

    蒲澤秀門, 細島康宏, 後藤佐和子, 忰田亮平, 斎藤亮彦, 成田一衛

    日本腎臓学会誌　61　(3)　241-241　2019/05/15

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  3. 自己末梢血幹細胞移植後に血栓性微小血管症(TMA)による腎障害を合併した一例

    白柏 由佳, 後藤 佐和子, 細島 康宏, 保坂 聖子, 山本 卓, 今井 直史, 伊藤 由美, 後藤 眞, 成田 一衛

    日本腎臓学会誌　60　(6)　876-876　2018/08

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

  4. SGLT2阻害薬ダパグリフロジンの腎近位尿細管細胞における血糖値非依存的なメガリン発現抑制作用

    飯田 倫理, 桑原 頌治, 細島 康宏, 石川 友美, 後藤 佐和子, 蒲澤 秀門, 忰田 亮平, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    糖尿病　61　(Suppl.1)　S-382　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

  5. Bardoxolone methylによる腎近位尿細管のメガリン調節機構の検討

    吉澤 優太, 桑原 頌治, 細島 康宏, 蒲澤 秀門, 忰田 亮平, 宇賀村 大亮, 後藤 佐和子, 飯田 倫理, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    糖尿病　61　(Suppl.1)　S-383　2018/04

    Publisher: (一社)日本糖尿病学会

    ISSN： 0021-437X

  6. Methotrexate大量療法後の高度排泄遅延および急性腎障害に対して血液浄化療法が有用であったALL患者の1例

    森紗世子, 後藤佐和子, 細島康宏, 山本卓, 成田一衛, 難波亜矢子, 後藤千尋, 柴崎康彦, 柴崎康彦, 増子正義, 曽根博仁, 島田泉, 鈴木直人, 外山聡

    東北腎不全研究会プログラム・抄録集　45th　2018

  7. Methotrexate大量療法後の高度排泄遅延および急性腎障害に対して血液浄化法が有用であったALL患者の1例

    森紗世子, 難波亜矢子, 後藤千尋, 柴崎康彦, 柴崎康彦, 増子正義, 曽根博仁, 後藤佐和子, 細島康宏, 山本卓, 成田一衛, 島田泉, 鈴木直人, 外山聡

    日本医療薬学会年会講演要旨集(Web)　28　2018

    ISSN： 2424-2470

  8. レーザアブレーション誘導結合プラズマ質量分析装置を用いた生体試料のPtイメージング分析

    堀孝太郎, 坂下明子, 花田一利, 井田巌, 藤本京子, 後藤佐和子, 斎藤亮彦

    日本分析化学会年会講演要旨集　66th　336　2017/08/26

  9. LC/MSを用いた選択的反応モニタリングによる臓器・体液の内因性アンジオテンシンペプチド定量法

    後藤佐和子, 吉田豊, 斎藤亮彦

    JSBMS Letters　42　(Supplement)　101　2017/08/25

    ISSN： 1881-5464

  10. 近位尿細管におけるダパグリフロジンによるメガリン機能調節作用

    飯田 倫理, 桑原 頌治, 細島 康宏, 石川 友美, 後藤 佐和子, 蒲澤 秀門, 忰田 亮平, 鈴木 芳樹, 成田 一衛, 斎藤 亮彦

    日本腎臓学会誌　59　(3)　284-284　2017/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  11. CHANGES IN URINARY POTASSIUM EXCRETION IN PATIENTS WITH CHRONIC KIDNEY DISEASE

    Yuichiro Ueda, Susumu Ookawara, Haruhisa Miyazawa, Kiyonori Ito, Sawako Goto, Taisuke Kitano, Mitsunobu Shindo, Yoshio Kaku, Keiji Hirai, Taro Hoshino, Honami Mori, Izumi Yoshida, Kaoru Tabei

    NEPHROLOGY DIALYSIS TRANSPLANTATION　30　2015/05

    DOI： 10.1093/ndt/gfv192.52 　

    ISSN： 0931-0509

    eISSN： 1460-2385

  12. FACTORS ASSOCIATED WITH EARLY PROGNOSIS AFTER DIALYSIS INITIATION

    Kiyonori Ito, Susumu Ookawara, Yuichiro Ueda, Haruhisa Miyazawa, Sawako Goto, Taisuke Kitano, Mitsutoshi Sindo, Yoshio Kaku, Keiji Hirai, Taro Hoshino, Aoi Nabata, Honami Mori, Izumi Yoshida, Kaoru Tabei

    NEPHROLOGY DIALYSIS TRANSPLANTATION　30　2015/05

    DOI： 10.1093/ndt/gfv192.50 　

    ISSN： 0931-0509

    eISSN： 1460-2385

  13. A NON-UNIFORMITY OF CHANGES IN SYSTEMIC BLOOD VOLUME INDUCED BY ULTRAFILTRATION DURING HEMODIALYSIS

    Susumu Ookawara, Kiyonori Ito, Sawako Goto, Yuichiro Ueda, Haruhisa Miyazawa, Taisuke Kitano, Mitsunobu Shindo, Yoshio Kaku, Keiji Hirai, Taro Hoshino, Honami Mori, Izumi Yoshida, Kaoru Tabei

    NEPHROLOGY DIALYSIS TRANSPLANTATION　30　2015/05

    DOI： 10.1093/ndt/gfv179.28 　

    ISSN： 0931-0509

    eISSN： 1460-2385

  14. 単純血漿交換が奏功した妊娠に伴う二次性高脂血症性膵炎の1例

    後藤佐和子, 吉田泉, 北野泰祐, 進藤充稔, 宮澤晴久, 植田裕一郎, 賀来佳男, 平井啓之, 星野太郎, 大河原晋, 田部井薫

    日本腎臓学会誌　56　(6)　850-850　2014/08/25

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  15. Fabry病様の電子顕微鏡所見を呈したブシラミンによる膜性腎症の一例

    宮澤晴久, 星野太郎, 北野泰佑, 進藤充稔, 後藤佐和子, 伊藤聖学, 植田裕一郎, 賀来佳男, 平井啓之, 森穂波, 吉田泉, 大河原晋, 山田茂樹, 田部井薫

    日本腎臓学会誌　56　(6)　854　2014/08/25

    ISSN： 0385-2385

  16. 心血管造影前後における血中・尿中バイオマーカーの変化

    後藤佐和子, 大河原晋, 豊島拓, 高橋徹也, 沓澤大輔, 桐林伸幸, 近江晃樹, 菅原重生, 田部井薫

    日本透析医学会雑誌　47　(Supplement 1)　1009　2014/05/28

    ISSN： 1340-3451

  17. ステロイド治療に奏功した拡張型心筋症様の病態を呈する心サルコイドーシスの一症例

    近江晃樹, 後藤佐和子, 豊島拓, 高橋徹也, 沓澤大輔, 桐林伸幸, 菅原重生, 伊藤啓明

    超音波医学　40　(6)　643　2013/11/15

    ISSN： 1346-1176

  18. 膜性腎症に抗リン脂質抗体症候群を合併した一例

    山陰周, 高崎聡, 高橋俊之, 後藤佐和子

    日本腎臓学会誌　55　(6)　1059　2013/08/25

    ISSN： 0385-2385

  19. 血液透析施行中の脳内局所酸素飽和度の観察

    後藤佐和子, 大河原晋, 田部井薫

    日本透析医学会雑誌　46　(Supplement 1)　490　2013/05/28

    ISSN： 1340-3451

  20. バイパス術後吻合部に形成された動脈瘤に対しコイル塞栓術を行ったもやもや病の1例

    熊谷孝, 渋間啓, 瀬尾恭一, 神宮字伸哉, 菅井努, 妻沼到, 井上明, 根元琢磨, 仁藤敏哉, 後藤佐和子

    山形県対脳卒中治療研究会会誌　(29)　9-14　2013/05/17

    Publisher: 山形県対脳卒中治療研究会事務局

    ISSN： 1345-3912

  21. ソフトドリンクケトーシス様症状で発症した1型糖尿病の1例

    後藤佐和子, 高瀬薫, 鈴木恵綾, 平山敦士, 稲毛雄一, 杉山和彦, 間中英夫

    糖尿病　56　(3)　199　2013/03/30

    ISSN： 0021-437X

  22. 神経線維腫症1型に合併した腎動脈狭窄病変に経皮的腎動脈形成術を施行し良好な拡張を得た一例

    渡部賢, 鈴木恵綾, 後藤佐和子, 玉田芳明, 間中英夫, 後藤敏和

    日本循環器学会東北地方会(Web)　157th　TOHOKU157,56 (WEB ONLY)　2013

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Books and Other Publications 2

  1. 体重管理が困難な透析患者への支援[総論]I 透析療法における体重管理の諸問題(1)血液透析療法における体重管理

    後藤 佐和子, 大河原 晋, 田部井 薫

    臨床透析　2014

  2. 専門医のための腎臓病学 第3版

    (医学書院・東京)

Presentations 10

  1. The role of Megalin in the Regulation of Renal RAS: Investigation Using LC/MS-Based Multiple-Reaction Monitoring Quantification of Angiotensin Peptides

    Goto Sawako, Yutaka Yoshida・Michihiro Hosojima, Tomomichi Iida, Hideyuki Kabasawa, Ryohei Kaseda・Ichiei Narita・Akihiko Saito

    Annual Meeting of American Society of Nephrology　2018/10/25

  2. Investigation of the role of megalin in the renal RAS by LC/MS-based multiple-reaction monitoring quantification of angiotensin peptides

    Sawako Goto, Yutaka Yoshida, Michihiro Hosojima, Shoji Kuwahara, Hideyuki Kabasawa, Ryohei Kaseda, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

    第61回日本腎臓学会学術総会　2018/06

  3. LC/MSを用いた選択的反応モニタリングによる臓器・体液の内因性アンジオテンシンペプチド定量法

    後藤 佐和子, 吉田 豊, 斎藤 亮彦

    第４２回日本医用マススペクトル学会年会　2017/09

  4. Stewart-Fencl法を利用した血液透析導入時における酸塩基平衡異常の検

    後藤 佐和子, 大河原 晋, 進藤 充稔, 北野 泰佑, 宮澤 晴久, 植田 裕一郎, 賀来 佳男, 星野 太郎, 吉田 泉, 田部井 薫

    第58回日本腎臓学会学術総会　2015/06

  5. 血液透析施行中の運動による循環動態および循環血液量変化の観察

    後藤佐和子, 大河原晋, 進藤充稔, 北野泰祐, 宮澤晴久, 植田裕一郎, 伊藤聖学, 賀来佳男, 平井啓之, 星野太郎, 名畑あおい, 森穂波, 吉田泉, 田部井薫

    第43回埼玉透析医学会学術 集会・総会　2014/11

  6. 単純血漿交換が奏功した妊娠に伴う二次性高脂血症性膵炎の1例

    後藤佐和子, 吉田泉, 北野泰祐, 進藤充稔, 宮澤晴久, 植田裕一郎, 賀来佳男, 平井啓之, 星野太郎, 大河原晋, 田部井薫

    第44回日本腎臓学会東部学術大会　2014/10

  7. 心血管造影前後における血中・尿中バイオマーカーの変化

    後藤佐和子, 大河原晋, 豊島拓, 高橋徹也, 沓澤大輔, 桐林伸幸, 近江晃樹, 菅原重生, 田部井薫

    第５９回日本透析医学会総会　2014/06

  8. 単純血漿交換療法が著効した後天性血友病Aの1症例

    後藤佐和子, 吉田泉, 蘆澤正弘, 進藤充稔, 北野泰祐, 宮澤晴久, 植田裕一郎, 賀来佳男, 平井啓之, 星野太郎, 名畑あおい, 森穂波, 大河原晋, 田部井薫

    日本アフェレシス学会 第23回関東甲信越地方会　2014/05

  9. 血液透析施行中の脳内局所酸素飽和度の観察

    後藤 佐和子, 大河原 晋, 田部井 薫

    第５８回日本透析医学会総会　2013/06

  10. 「ソフトドリンクケトーシス様症状で発症した1 型糖尿病の1 例」

    後藤 佐和子, 高瀬 薫, 間中 英夫

    第50 回日本糖尿病学会東北地方会　2012/11

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Industrial Property Rights 6

  1. 腎障害の抑制におけるシラスタチンの利用

    斎藤亮彦, 後藤佐和子, 平山吉朗, 関根盛

    特許第6548803号

    Property Type: Patent

  2. シクロデキストリン誘発腎障害の抑制

    斎藤亮彦,後藤佐和子,細島康宏,蒲澤秀門,平山吉朗

    Property Type: Patent

  3. 横紋筋融解により誘発される腎障害の抑制

    斎藤亮彦, 後藤佐和子, 平山吉朗

    Property Type: Patent

  4. 溶血反応により誘発される腎障害の抑制

    斎藤亮彦, 後藤佐和子, 平山吉朗

    Property Type: Patent

  5. 造影剤腎症のコバラミンを用いた新規予防法の開発

    斎藤亮彦, 後藤佐和子, 平山吉朗, 関根盛

    Property Type: Patent

  6. 質量分析計による腎臓，血液，尿のアンジオテンシンペプチドの定量法の開発

    斎藤 亮彦, 吉田 豊, 後藤 佐和子

    Property Type: Patent

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Research Projects 4

  1. メガリンと腎毒性リガンドの結合様式とメガリン拮抗薬の薬理機序の立体構造学的解析

    後藤 佐和子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究

    Category: 若手研究

    Institution: 新潟大学

    2022/04/01 - 2025/03/31

  2. メガリンの構造と機能の精密解析に基づく腎臓病の病態解明と診断・治療の新たな創薬

    斎藤 亮彦, 細島 康宏, 後藤 佐和子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 新潟大学

    2021/04/01 - 2025/03/31

    More details Close

    メガリンは近位尿細管上皮細胞に発現するエンドサイトーシス受容体で、糸球体を濾過する生理的リガンドの他、腎毒性のタンパク質や薬剤等の「入り口」分子として様々な腎臓病の発症・進展に関わる。本研究の目的は,我々が進めてきたメガリンの構造・機能解析を深化させ、腎臓病の病態解明と診断・治療における「メガリン創薬」を推進することである。具体的には、(A)メガリンの精密な立体構造解析やリガンド結合の物理化学的相互作用解析によって腎毒性リガンドとメガリンの結合様式を解明し、「メガリン拮抗薬」の開発を進める。(B)質量分析法等によるメガリンの構造解析を通して糖尿病性腎臓病の病態を解析し、「メガリン機能抑制薬」による治療理念を提唱する。(C)メガリンの細胞外ドメインの切断・尿中逸脱機序を明らかにすることで「尿中メガリン検査薬」の意義付けを深める。まず、(A) ラット腎から近位尿細管刷子縁膜を抽出・可溶化後、抗メガリンモノクローナル抗体によるアフィニティークロマトグラフィーおよびゲル濾過クロマトグラフィーによりメガリンを精製し、クライオ電子顕微鏡を用いて立体構造を明らかにした。その構造の詳細な解析により、メガリンが多様なリガンドと結合するメカニズムを解明した。また、インシリコ解析により、メガリン拮抗薬であるシラスタチンがメガリンを阻害するメカニズムを解析した。また、表面プラズモン共鳴法を利用して、新規メガリン拮抗薬をスクリーニングするための評価系の構築を行った。(B) マウス・ラット腎近位尿細管の細胞膜（微絨毛）および細胞内におけるメガリンの構造の違いによる分布性を、生化学的および免疫組織化学的に検証した。さらに、質量分析法等によるメガリンの構造解析の基礎検討を行った。また、(C) 2型糖尿病モデルdb/dbマウスにおいて、尿中細胞外ドメイン切断型メガリンの排泄機序の検討を行った。

  3. メガリンの構造と機能の精密解析に基づく腎臓病の病態解明と診断・治療の新たな創薬

    斎藤 亮彦, 後藤 佐和子, 細島 康宏

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 新潟大学

    2021/04/01 - 2025/03/31

  4. Investigation of the role of megalin in the renal renin-angiotensin system

    Goto Sawako

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Niigata University

    2019/04/01 - 2022/03/31

    More details Close

    Megalin, a proximal tubular endocytosis receptor, internalizes molecules involved in the renal renin-angiotensin (Ang) system, however, how megalin regulates the system remains elusive. We evaluated Ang peptides in the biological samples of kidney-specific megalin knockout (MegKO) mice and controls (Ctl) by using a novel mass spectrometry-based, parallel reaction monitoring assay for absolute quantification of Ang peptides. MegKO mice administered recombinant mouse angiotensinogen (rec-mAGT) suppressed the increase in the renal AngⅡ, the activation of renal ERK1/2 and proximal tubular Na+-H+ exchanger 3, with comparable renal Ang1-7 to that of Ctl mice. Urinary Na+ excretion of MegKO administered rec-mAGT was well maintained. Renal Ang-converting enzyme (ACE) and ACE2 were down- and up-regulated, respectively, in MegKO mice. Megalin downregulation may alleviate the pathological consequences of glomerular AGT hyperfiltration by shifting the ACE/AngⅡ axis to the ACE2/Ang1-7 axis.