Details of the Researcher

PHOTO

Yuji Oe
Section
Tohoku University Hospital
Job title
Senior Assistant Professor
e-Rad No.
00791980

Research History 7

  • 2026/04 - Present
    東北大学病院　腎臓・高血圧内科　講師

  • 2023/11 - 2026/03
    東北大学病院腎臓・高血圧内科　助教

  • 2021/09 - 2023/10
    カリフォルニア大学サンディエゴ校腎臓内科 訪問研究員

  • 2021/04 - 2021/07
    東北大学病院 血液浄化療法部 助教

  • 2019/04 - 2021/03
    Tohoku University　Tohoku Medical Megabank Organization, Department of Community Medical Supports

  • 2016/04 - 2019/03
    東北メディカル・メガバンク機構母児医科学分野　日本学術振興会特別研究員PD

  • 2012/04 - 2016/03
    東北大学医学系研究科腎高血圧内分泌学分野　博士課程

Show all Show first 5

Professional Memberships 3

  • THE JAPANESE SOCIETY FOR DIALYSIS THERAPY

  • JAPANESE SOCIETY OF NEPHROLOGY

  • THE JAPANESE SOCIETY OF INTERNAL MEDICINE

Research Areas 2

  • Life sciences / Experimental pathology /

  • Life sciences / Nephrology /

Awards 3

  1. Japan Kidney Council 2018 奨励賞

    2018

  2. 第39回日本高血圧学会総会YIA優秀賞

    2016

  3. 辛酉優秀学生賞特別賞

    2015　東北大学

Papers 67

  1. Systematic review and network meta-analysis for the 2026 update of the evidence-based clinical practice guidelines for the management with immunosuppressive therapies and biologic agents of membranous nephropathy

    Reiji Takami, Hiroki Nishiwaki, Yasushi Tsujimoto, Yuji Oe, Keisuke Onishi, Yuki Oba, Shinnosuke Sugihara, Yoshitaka Miyaoka, Mai Yoshida, Masahiko Yazawa, Tadashi Sofue, Izaya Nakaya, Takuji Ishimoto, Takehiko Kawaguchi, Noriaki Kurita, Sayaka Shimizu, Kengo Furuichi, Hirokazu Okada, Takehiko Wada

    Clinical and Experimental Nephrology　2026/09/19

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s10157-026-02944-4 　

    ISSN： 1342-1751

    eISSN： 1437-7799

  2. Disulfiram Attenuates Adenine‐Induced Renal Fibrosis by Modulating Inflammatory and Immunometabolic Responses

    Saori Kin, Yuji Oe, Shun Ishigaki, Ichiro Fujio, Mariko Miyazaki, Tetsuhiro Tanaka

    The FASEB Journal　40　(18)　2026/09/17

    Publisher: Wiley

    DOI： 10.1096/fj.202601271rr 　

    ISSN： 0892-6638

    eISSN： 1530-6860

    More details Close

    ABSTRACT Chronic kidney disease (CKD) is partly driven by excessive innate immune activation, which contributes to progressive renal injury and fibrosis. Disulfiram (DSF), an approved treatment for alcohol dependence, has recently emerged as an inhibitor of innate immune responses such as pyroptosis. In this study, we investigated whether DSF attenuates kidney injury in adenine‐induced nephropathy and explored the underlying mechanisms. DSF treatment markedly ameliorated kidney injury in adenine‐induced nephropathy, accompanied by suppression of inflammatory cell infiltration and inflammasome‐ and pyroptosis‐related markers. RNA sequencing revealed restoration of disrupted fatty acid metabolism in the kidneys following DSF treatment. Furthermore, DSF alleviated DNA damage, cellular senescence, and fibrosis. Importantly, activation of gasdermin D, a central executor of pyroptosis, was closely associated with disease severity in human CKD biopsy samples, supporting the clinical relevance of this pathway. Collectively, these findings suggest a potential role for DSF in modulating inflammatory and immunometabolic pathways in CKD.

  3. Genetic Testing Unveils a Novel Thrombospondin‐1 Domain Containing Protein 1 Gene Variant as the Cause of Chronic Edema in a 79‐Year‐Old Woman

    Eiko Amo, Takafumi Toyohara, Naoya Saijo, Satoko Sato, Jun Takayama, Yoshiko Suto, Yuji Noguchi, Sosuke Kinomura, Yusuke Ishizuka, Shun Watanabe, Koichi Kikuchi, Rui Makino, Mai Yoshida, Yuji Oe, Tasuku Nagasawa, Koji Okamoto, Takehiro Suzuki, Mariko Miyazaki, Shinya Kawaguchi, Takashi Suzuki, Takaaki Abe, Shigeo Kure, Atsuo Kikuchi, Tetsuhiro Tanaka

    Clinical Genetics　2026/09/09

    Publisher: Wiley

    DOI： 10.1111/cge.70247 　

    ISSN： 0009-9163

    eISSN： 1399-0004

    More details Close

    ABSTRACT Edema requires management tailored to its underlying etiology; however, in some cases the cause remains elusive. We describe a 79‐year‐old woman with lifelong unexplained peripheral edema. Comprehensive evaluation excluded common etiologies such as heart failure, renal dysfunction, and venous thrombosis. Whole‐genome sequencing identified a novel homozygous splice‐site variant (NM_018676.4:c.58+2T>G) in the thrombospondin‐1 domain–containing protein 1 ( THSD1 ) gene, which has previously been associated with non‐immune hydrops fetalis (NIHF). This report describes, to our knowledge, the first elderly patient with chronic peripheral edema harboring a likely pathogenic THSD1 variant, suggesting that THSD1‐related disease may, in rare instances, persist beyond the perinatal period and present into late adulthood. Although causality cannot be established definitively from a single case, the findings highlight the potential utility of genetic testing in adults with chronic unexplained edema.

  4. Glomerular hyperfiltration and enhanced sensitivity to kidney ischemia reperfusion with a blunted KIM-1 response in young male aging-accelerated SAMP8 mice. International-journal

    Helen A Goodluck, Sadhana Kanoo, Young Chul Kim, Natalia Lopez, Yuji Oe, Antonio Jose Martins Currais, Pamela Maher, Volker Vallon

    American journal of physiology. Renal physiology　330　(4)　F483-F497　2026/04/01

    DOI： 10.1152/ajprenal.00377.2025 　

    More details Close

    To better understand the impact of accelerated aging on kidney function, we compared standard C57BL6 mice (C57BL6) with senescence-accelerated mouse-prone 8 mice (SAMP8). Young male SAMP8 (3 and 6 mo) showed glomerular hyperfiltration compared with C57BL6 (absolute and per body weight), followed by gradual glomerular filtration rate (GFR) decline, lower blood pressure, and enhanced mortality over the first 15 mo of life. This was associated with higher kidney, heart, and liver but not brain weights. Female SAMP8 likewise showed a faster early rise in body weight, higher organ weights, and a somewhat higher mortality, but GFR and blood pressure appeared unaltered versus C57BL6. Since GFR phenotype was stronger in male mice, they were subjected to bilateral renal artery clamping-induced kidney ischemia reperfusion (IR). One day after IR, young SAMP8 (3 mo) showed higher plasma creatinine and kidney VCAM1 expression and subsequent mortality but a blunted rise in kidney Kim-1 mRNA and urine KIM-1 versus C57BL6. Kidney proteomics indicated suppressed pathways of phagocytosis and apoptosis but enhanced necroptosis in SAMP8 versus C57BL6. When ischemia time was lowered in SAMP8 to induce a similar initial rise in plasma creatinine and urine NGAL versus C57BL6, plasma creatinine recovery over 24 days was similar between strains in young mice, and despite impaired plasma creatinine recovery in older SAMP8 (10 mo) kidney injury or inflammation seemed not enhanced. In conclusion, male SAMP8 mice have a shortened life span, large kidneys, and at young age temporal hyperfiltration and enhanced sensitivity to IR-induced acute kidney injury associated with a blunted KIM-1 response.NEW & NOTEWORTHY The impact of accelerated aging on kidney function is incompletely understood. The current work shows that male mice of an accelerated aging mouse strain have a shortened lifespan that is associated with large kidneys. At young age, the mice have temporal glomerular hyperfiltration, reminiscent of the early diabetic kidney, and show enhanced sensitivity to renal ischemia reperfusion-induced acute kidney injury associated with a blunted upregulation of the tubular injury marker KIM-1.

  5. Editorial: Pathophysiology of Chronic Kidney Disease and Its Complications, Second Edition. International-journal

    Yuji Oe

    Biomedicines　14　(2)　2026/02/14

    DOI： 10.3390/biomedicines14020432 　

    More details Close

    The number of patients with chronic kidney disease (CKD) is increasing, and CKD is a major risk factor for progression to end-stage kidney disease (ESKD) requiring renal replacement therapy [...].

  6. Nicotinamide Attenuates Complement and Coagulation Pathways and Resultant Renal Fibrosis. International-journal

    Saori Kin, Yuji Oe, Taku Obara, Emiko Sato, Nobuyuki Takahashi, Mariko Miyazaki, Tetsuhiro Tanaka

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology　39　(23)　e71263　2025/12/15

    DOI： 10.1096/fj.202502028R 　

    More details Close

    The coagulation and complement pathways interact with each other, promoting inflammation and increasing thrombotic risk. However, their roles in chronic kidney disease (CKD) remain unclear. In our CKD cohort, elevated plasma fibrinogen and shortened prothrombin time were associated with higher serum complement C3 and C4 levels. Moreover, gene expression analysis of CKD renal tissues in public databases showed a positive correlation between fibrinogen β chain and C3 expression levels. Finally, tissue factor (factor III), fibrinogen, and C3 deposition and the genes related to coagulation and complement cascades were upregulated in fibrotic kidneys of mice treated with adenine or folic acid. To explore the modulators of these systems, the therapeutic effects of nicotinamide (NAM), a NAD+ precursor with anti-inflammatory and antithrombotic properties, were investigated. KEGG pathway analysis with RNA sequencing identified a significant inhibition of coagulation and complement cascades by NAM administration in adenine-induced nephropathy. Moreover, NAM suppressed innate immune responses associated with the prothrombotic state, including inflammasome and neutrophil extracellular trap formation. Collectively, these results suggest that excessive coagulation and complement activities are involved in the pathogenesis of CKD and are modulated by NAM.

  7. A case of malignant hypertension due to sarcoidosis. International-journal

    Sosuke Kinomura, Takafumi Toyohara, Yuki Chiba, Hidekazu Aoki, Yusuke Ishizuka, Yuji Noguchi, Saori Kin, Maho Akiu, Koichi Kikuchi, Rui Makino, Mai Yoshida, Yuji Oe, Tasuku Nagasawa, Koji Okamoto, Mariko Miyazaki, Hiroshi Sato, Kei Takase, Takaaki Abe, Tetsuhiro Tanaka

    Journal of hypertension　43　(10)　1721-1725　2025/10/01

    DOI： 10.1097/HJH.0000000000004110 　

    More details Close

    Sarcoidosis is a systemic inflammatory disease that is difficult to diagnose. This report describes a 54-year-old man who presented with an incidental finding of abnormal hilar shadows on imaging, indicating sarcoidosis. During follow-up, he experienced a sudden blood pressure increase (210/140 mmHg) accompanied by headaches, nausea, hypertensive retinopathy, and renal dysfunction, diagnosed as malignant hypertension. Contrast-enhanced computed tomography (CT) revealed wedge-shaped areas of poor enhancement in both kidneys, suggesting impaired perfusion due to interlobar artery compression. Renal biopsy showed noncaseating epithelioid cell granulomas, confirming renal sarcoidosis. After prednisolone treatment, the active renin concentration decreased from 265 pg/ml to 89 pg/ml, and the renal perfusion abnormalities improved on repeat CT. Renovascular hypertension due to sarcoidosis nodules disrupting the interlobar artery strongly suggests the cause of malignant hypertension. This is the first reported case of malignant hypertension due to renal sarcoidosis. Therefore, sarcoidosis should be considered as a differential diagnosis in patients with malignant hypertension.

  8. ASK1 limits kidney glucose reabsorption, growth, and mid-late proximal tubule KIM-1 induction when diabetes and Western diet are combined with SGLT2 inhibition. International-journal

    Maria Crespo-Masip, Helen A Goodluck, Young Chul Kim, Yuji Oe, Allie M Roach, Sadhana Kanoo, Natalia Lopez, Haiyan Zhang, Shawn S Badal, Volker Vallon

    American journal of physiology. Renal physiology　328　(5)　F662-F675　2025/05/01

    DOI： 10.1152/ajprenal.00031.2025 　

    More details Close

    Selonsertib is an apoptosis signal-regulating kinase 1 inhibitor (ASK1i) that attenuated the decline in creatinine-based estimated GFR in humans with type 2 diabetes and kidney disease but increased the rate of acute kidney injury. This study explored the individual and combined kidney effects of selonsertib and the antihyperglycemic sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in Western diet-fed male Akita mice, a murine model of early type 1 diabetes mellitus showing signs of systemic but no kidney inflammation. ASK1i reduced elevated plasma levels of proinflammatory cytokines/chemokines (IL-6, MCP1/CCL2, KC/CXCL1, and IP-10/CXCL10) without significantly changing hyperglycemia, glomerular hyperfiltration, and albuminuria or affecting the blood glucose and glomerular hyperfiltration-lowering effect of SGLT2i. A potential sign of tubular stress, SGLT2i modestly upregulated kidney cortex transcription of proinflammatory and profibrotic genes and distal tubule injury marker Ngal. Adding ASK1i to SGLT2i lowered the transcription of many of these genes, including Ngal. However, ASK1i enhanced kidney glucose reabsorption independent of SGLT2i, and combined ASK1i + SGLT2i increased kidney weight by 30%. This was associated with and positively correlated with the upregulation of the tubular stress/injury marker KIM-1, primarily in the mid-to-late proximal tubule. Combined ASK1i + SGLT2i increased the tubular injury score but not signs of kidney inflammation or fibrosis beyond a robust increase in kidney mRNA expression of Il6, Ccl2 (Mcp1), and Timp1, associated with increased plasma IL-6 levels. The data support the hypothesis that housekeeping functions of ASK1 limit glucose reabsorption and the associated growth and cellular stress induced in the mid-to-late proximal tubule by combining hyperglycemia and Western diet with SGLT2 inhibition.NEW & NOTEWORTHY Selonsertib is an apoptosis signal-regulating kinase 1 (ASK1) inhibitor that attenuated creatinine-based eGFR decline in humans with type 2 diabetes and kidney disease but increased acute kidney injury rates. Here, we report evidence in a murine model of early type 1 diabetes mellitus that housekeeping functions of ASK1 limit glucose reabsorption and the associated growth and cellular stress induced in the mid-to-late proximal tubule by combining hyperglycemia and Western diet with SGLT2 inhibition.

  9. Nicotinamide ameliorates podocyte injury and albuminuria in adriamycin-induced nephropathy. International-journal Peer-reviewed

    Kei Takahashi, Emiko Sato, Seiko Yamakoshi, Mizuki Ogane, Akiyo Sekimoto, Takamasa Ishikawa, Kiyomi Kisu, Yuji Oe, Koji Okamoto, Mariko Miyazaki, Tetsuhiro Tanaka, Nobuyuki Takahashi

    American journal of physiology. Renal physiology　2025/03/04

    DOI： 10.1152/ajprenal.00297.2024 　

    More details Close

    Podocytes are key components of the glomerular filtration barrier, and their injury leads to proteinuria, chronic kidney disease (CKD), and nephrotic syndrome. Effective treatments for these conditions are not well established, and prevention of podocyte injury is a crucial challenge. Nicotinamide (NAM), a form of vitamin B3, has been reported to exert beneficial effects in various renal disease models due to its antioxidant and anti-inflammatory properties and its ability to replenish nicotinamide adenine dinucleotide (NAD+). However, its impact on adriamycin (ADR)-induced nephropathy, a model of nephrotic syndrome caused by podocyte injury, remains unclear. We investigated the effects of NAM administration in a mouse model of ADR nephropathy. BALB/c mice were intravenously administered ADR to induce nephropathy. In the NAM-treated group, mice received 0.6% NAM in drinking water ad libitum starting 7 days before ADR administration. After 14 days, NAM treatment decreased albuminuria, glomerular sclerosis, and podocyte injury, and reduced inflammation and oxidative stress markers in the kidneys. NAM and NAD+ levels were decreased in ADR-treated kidneys, and the expression of the NAD+-consuming enzymes SIRT1 and PARP-1 was decreased and increased, respectively. Nicotinamide N-methyltransferase expression was increased. NAM canceled these abnormalities. In cultured rat podocytes, NAD+ alleviated ADR-induced cytotoxicity, apoptosis, and inflammation. These findings suggest that NAM prevents ADR nephropathy and podocyte injury, likely through NAD+ replenishment.

  10. The Many Faces of Protease-Activated Receptor 2 in Kidney Injury. International-journal Peer-reviewed

    Yuji Oe, Tetsuhiro Tanaka, Nobuyuki Takahashi

    Biomedicines　13　(2)　2025/02/08

    DOI： 10.3390/biomedicines13020414 　

    More details Close

    Protease-activated receptor 2 (PAR2) is a seven-transmembrane, G-protein-coupled receptor that is activated by coagulation proteases such as factor VIIa and factor Xa and other serine proteases. It is a potential therapeutic target for kidney injury, as it enhances inflammatory and fibrotic responses via the nuclear factor-kappa B and mitogen-activated protein kinase cascades. The body of knowledge regarding the role of PAR2 in kidney disease is currently growing, and its role in various kidney disease models, such as acute kidney injury, renal fibrosis, diabetic kidney disease, aging, and thrombotic microangiopathy, has been reported. Here, we review the literature to better understand the various aspects of PAR2 in kidney disease.

  11. Waldenström's Macroglobulinemia/Lymphoplasmacytic Lymphoma Developing Renal AA Amyloidosis: A Case Report and Literature Review. Peer-reviewed

    Yusuke Ishizuka, Yuji Oe, Sosuke Kinomura, Saori Kin, Yuji Noguchi, Koichi Kikuchi, Mai Yoshida, Rui Makino, Koji Okamoto, Tasuku Nagasawa, Takafumi Toyohara, Mariko Miyazaki, Hiroshi Sato, Yasushi Onishi, Hitoshi Warita, Tetsuhiro Tanaka

    Internal medicine (Tokyo, Japan)　2025/02/08

    DOI： 10.2169/internalmedicine.4678-24 　

    More details Close

    AA amyloidosis is a rare renal complication of Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL). A 66-year-old man with WM/LPL presented with nephrotic syndrome. A renal biopsy showed AA amyloidosis. Chemotherapy resulted in the remission of hematologic and nephrotic syndromes. Two years into follow-up, he became infected with COVID-19 and had massive proteinuria, despite no relapse of WM/LPL. A second renal biopsy confirmed a diagnosis of AA amyloidosis. However, increased prednisolone did not improve proteinuria. The patient ultimately died of cryptococcal meningitis. This case highlights the diverse spectrum of renal involvement in monoclonal IgM-secreting diseases and difficulty in managing fatal complications.

  12. Deep learning-based histopathological assessment of tubulo-interstitial injury in chronic kidney diseases. International-journal Peer-reviewed

    Nonoka Suzuki, Kaname Kojima, Silvia Malvica, Kenshi Yamasaki, Yoichiro Chikamatsu, Yuji Oe, Tasuku Nagasawa, Ekyu Kondo, Satoru Sanada, Setsuya Aiba, Hiroshi Sato, Mariko Miyazaki, Sadayoshi Ito, Mitsuhiro Sato, Tetsuhiro Tanaka, Kengo Kinoshita, Yoshihide Asano, Avi Z Rosenberg, Koji Okamoto, Kosuke Shido

    Communications medicine　5　(1)　3-3　2025/01/05

    DOI： 10.1038/s43856-024-00708-3 　

    More details Close

    BACKGROUND: Chronic kidney disease (CKD) causes progressive and irreversible damage to the kidneys. Renal biopsies are essential for diagnosing the etiology and prognosis of CKD, while accurate quantification of tubulo-interstitial injuries from whole slide images (WSIs) of renal biopsy specimens is challenging with visual inspection alone. METHODS: We develop a deep learning-based method named DLRS to quantify interstitial fibrosis and inflammatory cell infiltration as tubulo-interstitial injury scores, from WSIs of renal biopsy specimens. DLRS segments WSIs into non-tissue areas, glomeruli, tubules, interstitium, and arteries, and detects interstitial nuclei. It then quantifies these tubulo-interstitial injury scores using the segmented tissues and detected nuclei. RESULTS: Applied to WSIs from 71 Japanese CKD patients with diabetic nephropathy or benign nephrosclerosis, DLRS-derived scores show concordance with nephrologists' evaluations. Notably, the DLRS-derived fibrosis score has a higher correlation with the estimated glomerular filtration rate (eGFR) at biopsy than scores from nephrologists' evaluations. Validated on WSIs from 28 Japanese tubulointerstitial nephritis patients and 49 European-ancestry patients with nephrosclerosis, DLRS-derived scores show a significant correlation with eGFR. In an expanded analysis of 238 Japanese CKD patients, including 167 from another hospital, deviations in eGFR from expected values based on DLRS-derived scores correlate with annual eGFR decline after biopsy. Inclusion of these deviations and DLRS-derived fibrosis scores improve predictions of the annual eGFR decline. CONCLUSIONS: DLRS-derived tubulo-interstitial injury scores are concordant with nephrologists' evaluations and correlated with eGFR across different populations and institutions. The effectiveness of DLRS-derived scores for predicting annual eGFR decline highlights the potential of DLRS as a predictor of renal prognosis.

  13. Erratum for Waldenström's Macroglobulinemia/Lymphoplasmacytic Lymphoma Developing Renal AA Amyloidosis: A Case Report and Literature Review.

    Yusuke Ishizuka, Yuji Oe, Sosuke Kinomura, Saori Kin, Yuji Noguchi, Koichi Kikuchi, Mai Yoshida, Rui Makino, Koji Okamoto, Tasuku Nagasawa, Takafumi Toyohara, Mariko Miyazaki, Hiroshi Sato, Yasushi Onishi, Hitoshi Warita, Tetsuhiro Tanaka

    Internal medicine (Tokyo, Japan)　64　(12)　1951-1951　2025

    DOI： 10.2169/internalmedicine.E001-25 　

  14. Western diet exacerbates a murine model of Balkan nephropathy. International-journal

    Yuji Oe, Young Chul Kim, Sadhana Kanoo, Helen A Goodluck, Natalia Lopez, Jolene Diedrich, Antonio Michel Pinto, K Garrett Evensen, Antonio Jose Martins Currais, Pamela Maher, Volker Vallon

    American journal of physiology. Renal physiology　328　(1)　F15-F28　2025/01/01

    DOI： 10.1152/ajprenal.00185.2024 　

    More details Close

    Aristolochic acid (AA) ingestion causes Balkan nephropathy, characterized by tubular injury and progression to chronic kidney disease (CKD). AA is taken up by proximal tubule cells via organic anion transport and induces p21-mediated DNA damage response, but little is known about dietary modulating factors. Western diet (WD) is rich in saturated fats and sugars and can promote metabolic disorders and CKD progression. Here, we determined the impact of WD on AA-induced kidney injury. Five-week-old male C57BL/6J mice were fed WD or normal chow (NC) for 8 wk, followed by administration of AA every 3 days for 3 wk. Measurements were performed after the last injection and following a 3-wk recovery. Independent of dosing AA by body weight (3 mg/kg/day) or same dose/mouse (0.1125 mg/day), the AA-induced increase in plasma creatinine and reduction of hematocrit were greater in WD versus NC. This was associated with increased kidney gene expression in WD vs. NC of markers of DNA damage (p21), injury (Kim1 and Ngal), and inflammation (Tnfa) and kidney fibrosis staining. WD alone increased fractional excretion of indoxyl sulfate by 7.5-fold, indicating enhanced kidney organic anion transport. Kidney proteomics identified further WD-induced changes that could increase kidney sensitivity to AA and contribute to the altered response to AA including weakening of energy metabolism, potentiation of immune and infection pathways, and disruption in RNA regulation. In conclusion, WD can increase the susceptibility of mice to Balkan nephropathy, possibly in part through facilitating kidney uptake of the organic anion AA.NEW & NOTEWORTHY This study shows that a Western diet (WD) aggravates a murine model of Balkan nephropathy induced by the application of the organic anion and nephrotoxin aristolochic acid (AA). Mechanistically, this may involve WD-induced kidney organic anion secretion, which can facilitate the AA uptake into proximal tubular cells and thereby contribute to the injury. Kidney proteomics identified further changes induced by feeding a WD that could have increased the sensitivity of the kidney to stress and injury.

  15. Editorial for the Special Issue: Pathophysiology of Chronic Kidney Disease and Its Complications. International-journal

    Yuji Oe

    Biomedicines　12　(2)　2024/02/10

    DOI： 10.3390/biomedicines12020416 　

    More details Close

    Chronic kidney disease (CKD) is a risk factor for end-stage kidney disease, requiring renal replacement therapy [...].

  16. SGLT2 inhibitor dapagliflozin protects the kidney in a murine model of Balkan nephropathy. International-journal

    Yuji Oe, Young Chul Kim, Viktoriya S Sidorenko, Haiyan Zhang, Sadhana Kanoo, Natalia Lopez, Helen A Goodluck, Maria Crespo-Masip, Volker Vallon

    American journal of physiology. Renal physiology　326　(2)　F227-F240　2024/02/01

    DOI： 10.1152/ajprenal.00228.2023 　

    More details Close

    Proximal tubular uptake of aristolochic acid (AA) forms aristolactam (AL)-DNA adducts, which cause a p53/p21-mediated DNA damage response and acute tubular injury. Recurrent AA exposure causes kidney function loss and fibrosis in humans (Balkan endemic nephropathy) and mice and is a model of (acute kidney injury) AKI to chronic kidney disease (CKD) transition. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. C57BL/6J mice (15-wk-old) were administered vehicle or AA every 3 days for 3 wk (10 and 3 mg/kg ip in females and males, respectively). Dapagliflozin (dapa, 0.01 g/kg diet) or vehicle was initiated 7 days prior to AA injections. All dapa effects were sex independent, including a robust glycosuria. Dapa lowered urinary kidney-injury molecule 1 (KIM-1) and albumin (both normalized to creatinine) after the last AA injection and kidney mRNA expression of early DNA damage response markers (p53 and p21) 3 wk later at the study end. Dapa also attenuated AA-induced increases in plasma creatinine as well as AA-induced up-regulation of renal pro-senescence, pro-inflammatory and pro-fibrotic genes, and kidney collagen staining. When assessed 1 day after a single AA injection, dapa pretreatment attenuated AL-DNA adduct formation by 10 and 20% in kidney and liver, respectively, associated with reduced p21 expression. Initiating dapa application after the last AA injection also improved kidney outcome but in a less robust manner. In conclusion, the first evidence is presented that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.NEW & NOTEWORTHY Recurrent exposure to aristolochic acid (AA) causes kidney function loss and fibrosis in mice and in humans, e.g., in the form of the endemic Balkan nephropathy. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. Here we provide the first evidence in a murine model that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.

  17. Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

    Takehiko Wada, Sayaka Shimizu, Masahiro Koizumi, Tadashi Sofue, Hiroki Nishiwaki, Sho Sasaki, Izaya Nakaya, Yuji Oe, Takuji Ishimoto, Kengo Furuichi, Hirokazu Okada, Noriaki Kurita

    Clinical and experimental nephrology　2023/06/13

    DOI： 10.1007/s10157-023-02366-6 　

    More details Close

    BACKGROUND: With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). METHODS: This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. RESULTS: In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). CONCLUSION: Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

  18. CRRT 2023 Meeting: Targeting Amino Acid Transport to Improve Acute Kidney Injury Outcome. International-journal

    Yuji Oe, Volker Vallon

    Nephron　147　(12)　774-777　2023

    DOI： 10.1159/000531918 　

    More details Close

    BACKGROUND: In acute kidney injury (AKI), proximal tubules are a primary site of injury, resulting in significant alterations in amino acid transport and metabolism. However, little is known about the therapeutic potential of targeting amino acid transporters. Here, we briefly review the first experimental evidence that targeting the sodium-coupled amino acid transporter SLC6A19 (B0AT1) can improve AKI outcome. SUMMARY: SLC6A19 is expressed in the small intestine and early proximal tubules, where it absorbs and reabsorbs most of the ingested and filtered neutral amino acids, respectively. Systemic SLC6A19 deficiency alleviates renal cellular senescence and suppresses subsequent inflammation and fibrosis in a murine model of aristolochic acid-induced nephropathy, which targets the proximal tubule. The underlying mechanisms remain to be determined, but potentially may include reduced tubular workload, an inhibitory effect on SGLT2, downstream shift in transport and preconditioning of late proximal tubules, and induction of a fasting-like phenotype and lowering tubular accumulation of branched-chain amino acids, which all can promote tubular health.

  19. Tissue Factor, Thrombosis, and Chronic Kidney Disease. International-journal

    Yuji Oe, Nobuyuki Takahashi

    Biomedicines　10　(11)　2022/10/28

    DOI： 10.3390/biomedicines10112737 　

    More details Close

    Coagulation abnormalities are common in chronic kidney disease (CKD). Tissue factor (TF, factor III) is a master regulator of the extrinsic coagulation system, activating downstream coagulation proteases, such as factor Xa and thrombin, and promoting fibrin formation. TF and coagulation proteases also activate protease-activated receptors (PARs) and are implicated in various organ injuries. Recent studies have shown the mechanisms by which thrombotic tendency is increased under CKD-specific conditions. Uremic toxins, such as indoxyl sulfate and kynurenine, are accumulated in CKD and activate TF and coagulation; in addition, the TF-coagulation protease-PAR pathway enhances inflammation and fibrosis, thereby exacerbating renal injury. Herein, we review the recent research studies to understand the role of TF in increasing the thrombotic risk and CKD progression.

  20. Marked reduction of proteinuria after removal of a growth hormone-producing pituitary adenoma in a patient with focal segmental glomerulosclerosis: a case report and literature review.

    Shizuka Ishigaki, Yuji Oe, Kei Omata, Yoshikiyo Ono, Yuta Tezuka, Ryo Morimoto, Shun Watanabe, Hiroyasu Nishioka, Fumitoshi Satoh, Mai Yoshida, Rui Makino, Koji Okamoto, Tasuku Nagasawa, Naoko Inoshita, Shozo Yamada, Hiroshi Sato, Sadayoshi Ito, Mariko Miyazaki

    CEN case reports　2022/10/06

    DOI： 10.1007/s13730-022-00739-6 　

    More details Close

    Focal segmental glomerulosclerosis is a rare complication of acromegaly. A 74-year-old man was found to have acromegaly features such as enlargement of the forehead, nose, and hands. Laboratory tests showed a urine protein/creatinine ratio of 3.16 g/gCr and serum creatinine of 1.34 mg/dL. The levels of growth hormone and insulin-like growth factor I were markedly elevated, and the growth hormone level was not suppressed after 75 g oral glucose loading. Magnetic resonance imaging revealed a pituitary tumor with a diameter of 1.2 cm. Renal biopsy confirmed the diagnosis of focal segmental glomerulosclerosis. Transsphenoidal resection of the pituitary tumor led to remission of acromegaly and reduction in proteinuria highlighting the causal link between growth hormone overproduction and proteinuria. Treatment of acromegaly may be effective for acromegaly-associated focal segmental glomerulosclerosis.

  21. Aristolochic acid-induced nephropathy is attenuated in mice lacking the neutral amino acid transporter B0AT1 (Slc6a19) Peer-reviewed

    Aleix Navarro Garrido, Young Chul Kim, Yuji Oe, Haiyan Zhang, Maria Crespo-Masip, Helen A. Goodluck, Sadhana Kanoo, Paul W. Sanders, Stefan Bröer, Volker Vallon

    American Journal of Physiology-Renal Physiology　323　(4)　F455-F467　2022/10/01

    Publisher: American Physiological Society

    DOI： 10.1152/ajprenal.00181.2022 　

    ISSN： 1931-857X

    eISSN： 1522-1466

    More details Close

    Based on insights from studies manipulating glucose transport, the hypothesis has been proposed that inhibiting intestinal uptake or renal reabsorption of energy substrates has unique therapeutic potential to improve metabolic disease and kidney outcome in response to injury. The present study takes this idea to B0AT1, the major transporter for neutral amino acids in the intestine and kidney, and shows that its absence attenuates aristolochic acid-induced nephropathy.

  22. The Pathophysiological Basis of Diabetic Kidney Protection by Inhibition of SGLT2 and SGLT1 Peer-reviewed

    Yuji Oe, Volker Vallon

    Kidney and Dialysis　2　(2)　349-368　2022/06/18

    Publisher: MDPI AG

    DOI： 10.3390/kidneydial2020032 　

    eISSN： 2673-8236

    More details Close

    SGLT2 inhibitors can protect the kidneys of patients with and without type 2 diabetes mellitus and slow the progression towards end-stage kidney disease. Blocking tubular SGLT2 and spilling glucose into the urine, which triggers a metabolic counter-regulation similar to fasting, provides unique benefits, not only as an anti-hyperglycemic strategy. These include a low hypoglycemia risk and a shift from carbohydrate to lipid utilization and mild ketogenesis, thereby reducing body weight and providing an additional energy source. SGLT2 inhibitors counteract hyperreabsorption in the early proximal tubule, which acutely lowers glomerular pressure and filtration and thereby reduces the physical stress on the filtration barrier, the filtration of tubule-toxic compounds, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity and improved mitochondrial function and autophagy, can reduce pro-inflammatory, pro-senescence, and pro-fibrotic signaling and preserve tubular function and GFR in the long-term. By shifting transport downstream, SGLT2 inhibitors more equally distribute the transport burden along the nephron and may mimic systemic hypoxia to stimulate erythropoiesis, which improves oxygen delivery to the kidney and other organs. SGLT1 inhibition improves glucose homeostasis by delaying intestinal glucose absorption and by increasing the release of gastrointestinal incretins. Combined SGLT1 and SGLT2 inhibition has additive effects on renal glucose excretion and blood glucose control. SGLT1 in the macula densa senses luminal glucose, which affects glomerular hemodynamics and has implications for blood pressure control. More studies are needed to better define the therapeutic potential of SGLT1 inhibition to protect the kidney, alone or in combination with SGLT2 inhibition.

  23. Glomerulonephritis Associated with Infective Endocarditis Showing Serological Positivity for PR3-anti-neutrophil Cytoplasmic Antibody and Anti-glomerular Basement Membrane Antibody. Peer-reviewed

    Yuki Chiba, Kei Takahashi, Rui Makino, Mai Yoshida, Yuji Oe, Tasuku Nagasawa, Hiroshi Sato, Mariko Miyazaki, Koji Okamoto

    Internal medicine (Tokyo, Japan)　61　(14)　2179-2185　2021/12/28

    DOI： 10.2169/internalmedicine.8385-21 　

    More details Close

    We herein report a case of crescentic glomerulonephritis associated with infective endocarditis (IE). A 61-year-old-woman presented with a fever and renal dysfunction and was diagnosed with IE. The patient was positive for PR3-ANCA and anti-GBM antibodies. Renal biopsy findings showed crescentic glomerulonephritis with isolated deposition of C3c, a serum conversion product of complement C3. Given these clinical findings, the patient was diagnosed with IE-associated glomerulonephritis. Antibiotic therapy was continued without immunosuppressive agents. After the initiation of the antibiotics, the fever resolved, and the renal function gradually recovered. This case highlights the notion that laboratory findings should be carefully evaluated with reference to other findings.

  24. A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020.

    Takehiko Wada, Takuji Ishimoto, Izaya Nakaya, Takehiko Kawaguchi, Tadashi Sofue, Sayaka Shimizu, Noriaki Kurita, Sho Sasaki, Hiroki Nishiwaki, Masahiro Koizumi, Shoji Saito, Nobuhiro Nishibori, Yuji Oe, Mai Yoshida, Yoshitaka Miyaoka, Shin'ichi Akiyama, Yuya Itano, Masaki Okazaki, Takaya Ozeki, Daisuke Ichikawa, Hideyo Oguchi, Satoshi Kohsaka, Shiho Kosaka, Yuki Kataoka, Hideaki Shima, Sayuri Shirai, Kazuhiro Sugiyama, Tomo Suzuki, Daisuke Son, Tomomi Tanaka, Eishu Nango, Kakuya Niihata, Yoko Nishijima, Kandai Nozu, Midori Hasegawa, Rei Miyata, Masahiko Yazawa, Yoshihiro Yamamoto, Ryohei Yamamoto, Yugo Shibagaki, Kengo Furuichi, Hirokazu Okada, Ichiei Narita

    Clinical and experimental nephrology　25　(12)　1277-1285　2021/12

    DOI： 10.1007/s10157-021-02098-5 　

  25. Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet Peer-reviewed

    Shu Yamakage, Yuji Oe, Emiko Sato, Koji Okamoto, Akiyo Sekimoto, Satoshi Kumakura, Hiroshi Sato, Mai Yoshida, Tasuku Nagasawa, Mariko Miyazaki, Sadayoshi Ito, Nigel Mackman, Nobuyuki Takahashi

    Scientific Reports　11　(1)　2021/12

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-021-91586-5 　

    eISSN： 2045-2322

    More details Close

    <title>Abstract</title>Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases. However, the role of monocyte myeloid cell TF in CKD progression remains unclear. We aimed to clarify this issue, and the present study found that patients with CKD had elevated levels of D-dimer, a marker of fibrin degradation, which was associated with decreased estimated glomerular filtration rate and increased serum levels of uremic toxins, such as indoxyl sulfate. In vitro studies showed that several uremic toxins increased cellular TF levels in monocytic THP-1 cells. Mice with TF specifically deleted in myeloid cells were fed an adenine diet to cause uremic kidney injury. Myeloid TF deletion reduced tubular injury and pro-inflammatory gene expression in the kidneys of adenine-induced CKD but did not improve renal function as measured by plasma creatinine or blood urea nitrogen. Collectively, our findings suggest a novel concept of pathogenesis of coagulation-mediated kidney injury, in which elevated TF levels in monocytes under uremic conditions is partly involved in the development of CKD.

  26. A Novel Mutation in LMX1B (p.Pro219Ala) Causes Focal Segmental Glomerulosclerosis with Alport Syndrome-like Phenotype. Peer-reviewed

    Yuji Oe, Eikan Mishima, Takayasu Mori, Koji Okamoto, Yohei Honkura, Tasuku Nagasawa, Mai Yoshida, Hiroshi Sato, Jun Suzuki, Ryoukichi Ikeda, Eisei Sohara, Shinichi Uchida, Yukio Katori, Mariko Miyazaki

    Internal medicine (Tokyo, Japan)　60　(18)　2991-2996　2021/04/05

    DOI： 10.2169/internalmedicine.6987-20 　

    More details Close

    A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.

  27. Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet Peer-reviewed

    Yuji Oe, Shohei Mitsui, Emiko Sato, Naoko Shibata, Kiyomi Kisu, Akiyo Sekimoto, Mariko Miyazaki, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

    The American Journal of Pathology　191　(2)　283-293　2021/02

    Publisher: Elsevier BV

    DOI： 10.1016/j.ajpath.2020.10.012 　

    ISSN： 0002-9440

  28. Spontaneous remission of minimal change nephrotic syndrome in an elderly man. Peer-reviewed

    Yuki Chiba, Tasuku Nagasawa, Saori Kin, Kei Takahashi, Mai Yoshida, Yuji Oe, Koji Okamoto, Hiroshi Sato, Mariko Miyazaki

    CEN case reports　10　(2)　301-307　2021/01/04

    DOI： 10.1007/s13730-020-00554-x 　

    More details Close

    Minimal change nephrotic syndrome (MCNS) cases achieving spontaneous remission without external factors are rarely reported. We report a case of MCNS that achieved spontaneous remission without external factors that triggered its onset. An 82-year-old male patient was admitted to the hospital for close examination of nephrotic syndrome. Renal biopsy was performed and MCNS was diagnosed. Owing to the patient's age and history of foot and microvascular arteriovenous thrombosis, we did not start immunosuppressive drugs, including steroids, and opted for conservative management. After conservative treatment, proteinuria gradually decreased, and the patient achieved complete remission. Given that the patient had a history of urinary protein and thrombosis, recurrence of MCNS was considered again this time. In addition, the involvement of external factors that trigger the onset of MCNS was not found. In conclusion, in elderly-onset MCNS, clinicians generally hesitate to initiate treatment with an immunosuppressive drug, containing steroids, because of its many complications. Thus, our data provide valuable insight into MCNS.

  29. Coagulation, Protease-Activated Receptors, and Diabetic Kidney Disease: Lessons from eNOS-Deficient Mice Peer-reviewed

    Yuji Oe, Mariko Miyazaki, Nobuyuki Takahashi

    The Tohoku Journal of Experimental Medicine　255　(1)　1-8　2021

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.255.1 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  30. Questionnaire survey on the prescription of renal replacement therapy for acute phase patients on maintenance dialysis who developed cerebrovascular disease Peer-reviewed

    Maho Akiu, Tae Yamamoto, Emi Fujikura, Koji Okamoto, Atsuhiro Nakagawa, Mai Yoshida, Takashi Nakamichi, Taro Fukushi, Tasuku Nagasawa, Yuji Oe, Masaaki Nakayama, Hiroshi Sato, Teiji Tominaga, Sadayoshi Ito, Hideo Harigae, Mariko Miyazaki

    Clinical and Experimental Nephrology　24　(9)　821-828　2020/09

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s10157-020-01905-9 　

    ISSN： 1342-1751

    eISSN： 1437-7799

    More details Close

    BACKGROUND: There is limited information about acute phase renal replacement therapy (RRT) for maintenance hemodialysis patients after the onset of cerebrovascular disease. This study aimed to investigate which modality of renal replacement therapy is currently selected in practice. METHODS: We conducted a mail-based survey in 317 dialysis facilities that were certified by three academic societies that focus on dialysis, neurology, and neurosurgery in Japan. RESULTS: We received responses from 103 facilities (32.5%). In cases of cerebral infarction (CI) and intracerebral hemorrhage (ICH), more than 80% of the facilities selected only intermittent RRT, and 22.3% (CI)/8.7% (ICH) of the facilities selected intermittent HD which is the same setting in normal conditions. Although continuous hemodiafiltration and peritoneal dialysis are recommended in the Japanese guidelines, these were selected in only a few facilities: 16.5% and 0% in CI, 16.5% and 1% in ICH, respectively. RRT on the day of onset tended to be avoided, irrespective of the duration following the last HD session. Furthermore, physicians preferred to modify anticoagulants and reduce dialysis performance in the acute phase. CONCLUSION: This questionnaire survey uncovered a gap between guidelines and actual practice, even in hospitals accredited as educational facility, which is a novel and important finding. Further studies with larger sample sizes are needed to determine the optimal modality of RRT for the acute phase of cerebrovascular disease.

  31. The effect of aldosterone on adiposity - The role of glucose absorption in the small intestine International-journal Peer-reviewed

    Hidekazu Shirai, Emiko Sato, Akiyo Sekimoto, Taeko Uchida, Yuji Oe, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    Biochemical and Biophysical Research Communications　531　(4)　628-635　2020/08

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2020.07.119 　

    ISSN： 0006-291X

    More details Close

    We have previously demonstrated that manipulation of the renin angiotensin system (RAS) has large effects on digestive efficiency. However, the effects of aldosterone on body weight, adiposity, and glucose absorption in the intestine remains unknown. We here demonstrated that lack of aldosterone synthase (ASKO) in mice did not affect adiposity. In contrast, mice administered with aldosterone were resistant to diet-induced obesity. This is due to gastrointestinal loss of dietary glucose. As expected, ASKO mice had increased glucose absorption, whereas mice administered with aldosterone had reduced glucose absorption in the small intestine. Furthermore, the level of protein expression of sodium glucose transporter 1 (SGLT1) in the mucosa of the jejunum was higher in ASKO mice, and lower in mice administered with aldosterone than control mice. Our findings indicate that aldosterone plays an important role on SGLT-1-mediated glucose absorption in the small intestine.

  32. Metabolomics of a mouse model of preeclampsia induced by overexpressing soluble fms-like tyrosine kinase 1. International-journal Peer-reviewed

    Emiko Sato, Yukako Tsunokuni, Manami Kaneko, Daisuke Saigusa, Ritsumi Saito, Shuichi Shimma, Akiyo Sekimoto, Yoshiko Kawana, Yuji Oe, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    Biochemical and biophysical research communications　527　(4)　1064-1071　2020/07/05

    DOI： 10.1016/j.bbrc.2020.04.079 　

    More details Close

    Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model. To generate the PE model, a recombinant adenovirus to overproduce soluble fms-like tyrosine kinase 1 (sFlt-1) was administered to mice (Jcl:ICR) at 8.5 day post-coitum (dpc). Plasma and placenta samples were harvested at 12.5 dpc. Fetal and placental weight was significantly decreased at 12.5 dpc in PE mice. Plasma and placental acylcarnitine levels were significantly higher in PE mice than those in control mice. Glycolysis was accelerated and glucose metabolic flow was altered with hypoxia, leading to ATP shortage in the labyrinth of PE mice. In PE mice, ATP production was diminished, and fatty acid oxidation was accelerated in the placenta, consequently, blood carnitine and acylcarnitine levels were increased. The mitochondrial morphology in BeWo cells was impaired under hypoxia. Nicotinamide treatment reversed fetal growth restriction, placental development, and altered metabolic flow in the early stage in PE. In addition, nicotinamide normalized impaired mitochondrial morphology. Hence, targeting this metabolic alteration in the placenta using nicotinamide may serve as a potential therapeutic approach for PE treatment.

  33. Protease-activated receptor 2 contributes to placental development and fetal growth in mice. International-journal Peer-reviewed

    Shu Yamakage, Yuji Oe, Akiyo Sekimoto, Hirofumi Obata, Miho Yasuta, Emiko Sato, Satoshi Kumakura, Hiroshi Sato, Junichi Sugawara, Sadayoshi Ito, Nobuyuki Takahashi

    Thrombosis research　193　173-179　2020/07/02

    DOI： 10.1016/j.thromres.2020.06.039 　

    More details Close

    BACKGROUND: Protease-activated receptor 2 (PAR2) is activated by serine proteases such as coagulation tissue factor/VIIa complex, factor Xa or trypsin and is pro-angiogenic in several disease models. Impaired angiogenesis in placenta causes placental dysfunction and fetal growth restriction. PAR2 is expressed in the placenta trophoblast. However, the role of PAR2 in pregnancy remains unknown. OBJECTIVE: The present study aimed to examine the role of PAR2 in placental development and fetal growth using a murine model. METHODS: PAR2-/- or PAR2+/+ mice in the ICR background were used. Female PAR2-/- mice were mated with male PAR2-/- mice, and female PAR2+/+ mice were mated with male PAR2+/+ mice to obtain PAR2-/- and PAR2+/+ fetuses, respectively. The day a virginal plug was observed in the morning was determined as 0.5-day post-coitum (dpc). Pregnant mice were sacrificed on 13.5 or 18.5 dpc to collect samples. RESULTS: A deficiency of PAR2 significantly reduced the fetal and placental weight and impaired placental labyrinth development in mice on 18.5 dpc. Collagen IV expression in placenta labyrinth was smaller in PAR2 knockout mice compared to that of wild-type mice. A deficiency of PAR2 also reduced the expression levels of genes related to angiogenesis and coagulation in placenta. CONCLUSION: Our data suggest that PAR2 is required for fetal growth and angiogenesis in the placenta and is thus important for a normal pregnancy.

  34. Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition

    Emiko Sato, Koji Hosomi, Akiyo Sekimoto, Eikan Mishima, Yuji Oe, Daisuke Saigusa, Sadayoshi Ito, Takaaki Abe, Hiroshi Sato, Jun Kunisawa, Toshimitsu Niwa, Nobuyuki Takahashi

    Biochemical and Biophysical Research Communications　525　(3)　773-779　2020/05/07

    Publisher: Elsevier B.V.

    DOI： 10.1016/j.bbrc.2020.02.141 　

    ISSN： 1090-2104 0006-291X

  35. Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease International-journal Peer-reviewed

    Shohei Mitsui, Yuji Oe, Akiyo Sekimoto, Emiko Sato, Yamato Hashizume, Shu Yamakage, Satoshi Kumakura, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

    American Journal of Physiology-Renal Physiology　318　(5)　F1067-F1073　2020/05/01

    Publisher: American Physiological Society

    DOI： 10.1152/ajprenal.00595.2019 　

    ISSN： 1931-857X

    eISSN： 1522-1466

    More details Close

    Protease-activated receptors (PARs) are coagulation protease targets, and they increase expression of inflammatory cytokines and chemokines in various diseases. Of all PARs, previous reports have shown that PAR1 or PAR2 inhibition is protective against diabetic glomerular injury. However, how PAR1 and PAR2 cooperatively contribute to diabetic kidney disease (DKD) pathogenesis and whether dual blockade of PARs is more effective in DKD remain elusive. To address this issue, male type I diabetic Akita mice heterozygous for endothelial nitric oxide synthase were used as a model of DKD. Mice (4 mo old) were divided into four treatment groups and administered vehicle, PAR1 antagonist (E5555, 60 mg·kg−1·day−1), PAR2 antagonist (FSLLRY, 3 mg·kg−1·day−1), or E5555 + FSLLRY for 4 wk. The results showed that the urinary albumin creatinine ratio was significantly reduced when both PAR1 and PAR2 were blocked with E5555 + FSLLRY compared with the vehicle-treated group. Dual blockade of PAR1 and PAR2 by E5555 + FSLLRY additively ameliorated histological injury, including mesangial expansion, glomerular macrophage infiltration, and collagen type IV deposition. Marked reduction of inflammation- and fibrosis-related gene expression in the kidney was also observed. In vitro, PAR1 and PAR2 agonists additively increased mRNA expression of macrophage chemoattractant protein 1 or plasminogen activator inhibitor-1 in human endothelial cells. Changes induced by the PAR1 agonist were blocked by a NF-κB inhibitor, whereas those of the PAR2 agonist were blocked by MAPK and/or NF-κB inhibitors. These findings suggest that PAR1 and PAR2 additively contribute to DKD pathogenesis and that dual blockade of both could be a novel therapeutic option for treatment of patients with DKD.

  36. Longitudinal plasma amino acid profiling with maternal genomic background throughout human pregnancy International-journal Peer-reviewed

    Matsuyuki Shirota, Daisuke Saigusa, Riu Yamashita, Yasutake Kato, Mitsuyo Matsumoto, Junya Yamagishi, Noriko Ishida, Kazuki Kumada, Yuji Oe, Hisaaki Kudo, Junji Yokozawa, Yoko Kuroki, Ikuko Motoike, Fumiki Katsuoka, Masao Nagasaki, Seizo Koshiba, Keiko Nakayama, Osamu Tanabe, Jun Yasuda, Shigeo Kure, Kengo Kinoshita, Hirohito Metoki, Shinichi Kuriyama, Nobuo Yaegashi, Masayuki Yamamoto, Junichi Sugawara

    Medical Mass Spectrometry　4　(1)　36-49　2020/04/16

    DOI： 10.24508/mms.2020.06.001 　

  37. Uremic toxins alter coagulation and fibrinolysis-related genes expression in human endothelial cells International-journal Peer-reviewed

    Yuji Oe, Emiko Sato, Hiroshi Sato, Mariko Miyazaki, Sadayoshi Ito, Nobuyuki Takahashi

    Thrombosis Research　186　75-77　2020/02

    Publisher: Elsevier BV

    DOI： 10.1016/j.thromres.2019.12.017 　

    ISSN： 0049-3848

  38. Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. International-journal Peer-reviewed

    Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Fumika Nanto-Hara, Jiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching-Chin Yang, Chitose Suzuki, Matthew C Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

    Nature communications　10　(1)　1835-1835　2019/04/23

    DOI： 10.1038/s41467-019-09735-4 　

    More details Close

    Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

  39. Glomerular Injury Is Exacerbated in Lupus-Prone MRL/lpr Mice Treated with a Protease-Activated Receptor 2 Antagonist

    Rina Itto, Yuji Oe, Kenta Imaruoka, Emiko Sato, Akiyo Sekimoto, Shu Yamakage, Satoshi Kumakura, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

    The Tohoku Journal of Experimental Medicine　249　(2)　127-133　2019

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.249.127 　

    ISSN： 0040-8727

    eISSN： 1349-3329

  40. Protease-activated receptor 2 protects against VEGF inhibitor-induced glomerular endothelial and podocyte injury. Peer-reviewed

    Oe Y, Fushima T, Sato E, Sekimoto A, Kisu K, Sato H, Sugawara J, Ito S, Takahashi N

    Sci Rep　9　(1)　2986　2019

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1038/s41598-019-39914-8 　

    eISSN： 2045-2322

  41. Nicotinamide alleviates kidney injury and pregnancy outcomes in lupus-prone MRL/lpr mice treated with lipopolysaccharide. Peer-reviewed

    Imaruoka K, Oe Y(equal contribution, Fushima T, Sato E, Sekimoto A, Sato H, Sugawara J, Ito S, Takahashi N

    Biochem Biophys Res Commun　510　(4)　587-593-593　2019

    Publisher: Elsevier BV

    DOI： 10.1016/j.bbrc.2019.01.110 　

    ISSN： 0006-291X

  42. Protease-activated receptor 2 exacerbates cisplatin-induced nephrotoxicity Peer-reviewed

    Watanabe M, Oe Y(equal contribution, Sato E, Sekimoto A, Sato H, Ito S, Takahashi N

    Am J Physiol Renal Physiol　316　F654-F659　2019

  43. Vitamin B3 nicotinamide: A promising candidate for treating preeclampsia and improving fetal growth Invited Peer-reviewed

    Nobuyuki Takahashi, Feng Li, Tomofumi Fushima, Gen Oyanagi, Emiko Sato, Yuji Oe, Akiyo Sekimoto, Daisuke Saigusa, Hiroshi Sato, Sadayoshi Ito

    Tohoku Journal of Experimental Medicine　244　(3)　243-248　2018/03/01

    Publisher: Tohoku University Medical Press

    DOI： 10.1620/tjem.244.243 　

    ISSN： 1349-3329 0040-8727

  44. Hepatic dysfunction and thrombocytopenia induced by excess sFlt1 in mice lacking endothelial nitric oxide synthase. Peer-reviewed

    Oe Y, Ko M, Fushima T, Sato E, Karumanchi SA, Sato H, Sugawara J, Ito S, Takahashi N

    Sci Rep　8　(1)　102　2018

  45. Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques. International-journal Peer-reviewed

    Emiko Sato, Daisuke Saigusa, Eikan Mishima, Taeko Uchida, Daisuke Miura, Tomomi Morikawa-Ichinose, Kiyomi Kisu, Akiyo Sekimoto, Ritsumi Saito, Yuji Oe, Yotaro Matsumoto, Yoshihisa Tomioka, Takefumi Mori, Nobuyuki Takahashi, Hiroshi Sato, Takaaki Abe, Toshimitsu Niwa, Sadayoshi Ito

    Toxins　10　(1)　E19　2017/12/28

    DOI： 10.3390/toxins10010019 　

    More details Close

    Elevated circulating uremic toxins are associated with a variety of symptoms and organ dysfunction observed in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are representative uremic toxins that exert various harmful effects. We recently showed that IS induces metabolic alteration in skeletal muscle and causes sarcopenia in mice. However, whether organ-specific accumulation of IS and PCS is associated with tissue dysfunction is still unclear. We investigated the accumulation of IS and PCS using liquid chromatography/tandem mass spectrometry in various tissues from mice with adenine-induced CKD. IS and PCS accumulated in all 15 organs analyzed, including kidney, skeletal muscle, and brain. We also visualized the tissue accumulation of IS and PCS with immunohistochemistry and mass spectrometry imaging techniques. The oral adsorbent AST-120 prevented some tissue accumulation of IS and PCS. In skeletal muscle, reduced accumulation following AST-120 treatment resulted in the amelioration of renal failure-associated muscle atrophy. We conclude that uremic toxins can accumulate in various organs and that AST-120 may be useful in treating or preventing organ dysfunction in CKD, possibly by reducing tissue accumulation of uremic toxins.

  46. Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure Peer-reviewed

    Tomofumi Fushima, Akiyo Sekimoto, Yuji Oe, Emiko Sato, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY　312　(2)　F366-F372　2017/02

    DOI： 10.1152/ajprenal.00501.2016 　

    ISSN： 1931-857X

    eISSN： 1522-1466

  47. Nicotinamide ameliorates a preeclampsia-like condition in mice with reduced uterine perfusion pressure Peer-reviewed

    Tomofumi Fushima, Akiyo Sekimoto, Yuji Oe, Emiko Sato, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    American Journal of Physiology - Renal Physiology　312　(2)　F366-F372　2017

    Publisher: American Physiological Society

    DOI： 10.1152/ajprenal.00501.2016 　

    ISSN： 1522-1466 0363-6127

  48. Protease-activated receptor 2 exacerbates adenine-induced renal tubulointerstitial injury in mice Peer-reviewed

    Sakiko Hayashi, Yuji Oe, Tomofumi Fushima, Emiko Sato, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　483　(1)　547-552　2017/01

    DOI： 10.1016/j.bbrc.2016.12.108 　

    ISSN： 0006-291X

    eISSN： 1090-2104

  49. Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia Peer-reviewed

    Feng Li, Tomofumi Fushima, Gen Oyanagi, H. W. Davin Townley-Tilson, Emiko Sato, Hironobu Nakada, Yuji Oe, John R. Hagaman, Jennifer Wilder, Manyu Li, Akiyo Sekimoto, Daisuke Saigusa, Hiroshi Sato, Sadayoshi Ito, J. Charles Jennette, Nobuyo Maeda, S. Ananth Karumanchi, Oliver Smithies, Nobuyuki Takahashi

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA　113　(47)　13450-13455　2016/11

    DOI： 10.1073/pnas.1614947113 　

    ISSN： 0027-8424

  50. Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease Peer-reviewed

    Emiko Sato, Takefumi Mori, Eikan Mishima, Arisa Suzuki, Sanae Sugawara, Naho Kurasawa, Daisuke Saigusa, Daisuke Miura, Tomomi Morikawa-Ichinose, Ritsumi Saito, Ikuko Oba-Yabana, Yuji Oe, Kiyomi Kisu, Eri Naganuma, Kenji Koizumi, Takayuki Mokudai, Yoshimi Niwano, Tai Kudo, Chitose Suzuki, Nobuyuki Takahashi, Hiroshi Sato, Takaaki Abe, Toshimitsu Niwa, Sadayoshi Ito

    SCIENTIFIC REPORTS　6　36618　2016/11

    DOI： 10.1038/srep36618 　

    ISSN： 2045-2322

  51. Effects of cyclophosphamide on the prognosis of Japanese patients with renal vasculitis associated with anti-neutrophil cytoplasmic antibody-positive microscopic polyangiitis Peer-reviewed

    Masashi Iwabuchi, Izaya Nakaya, Yoshinori Tsuchiya, Yugo Shibagaki, Takuhiro Yamaguchi, Shunichi Fukuhara, Yuji Oe, Tsutomu Sakuma, Toshinobu Sato, Yoshio Taguma, Jun Soma

    CLINICAL AND EXPERIMENTAL NEPHROLOGY　20　(5)　712-719　2016/10

    DOI： 10.1007/s10157-015-1200-5 　

    ISSN： 1342-1751

    eISSN： 1437-7799

  52. AN ORAL FACTOR XA INHIBITOR, EDOXABAN, ALLEVIATES DIABETIC NEPHROPATHY IN MICE LACKING eNOS

    Oe Yuji, Fushima Tomofumi, Sato Emiko, Sato Hiroshi, Ito Sadayoshi, Takahashi Nobuyuki

    JOURNAL OF HYPERTENSION　34　E102　2016/09

    DOI： 10.1097/01.hjh.0000500125.77396.fa 　

    ISSN： 0263-6352

  53. IGA NEPHROPATHY IS EXACERBATED BY PREGNANCY AND IS A RISK FACTOR FOR PREECLAMPSIA IN GROUPED DDY MICE

    Fushima Tomofumi, Oe Yuji, Sato Emiko, Suzuki Yusuke, Tomino Yasuhiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

    JOURNAL OF HYPERTENSION　34　E427　2016/09

    DOI： 10.1097/01.hjh.0000501101.72126.01 　

    ISSN： 0263-6352

  54. PAR2 SIGNALING EXACERBATES DIABETIC NEPHROPATHY

    Oe Yuji, Hayashi Sakiko, Fushima Tomofumi, Sato Emiko, Kisu Kiyomi, Sato Hiroshi, Ito Sadayoshi, Takahashi Nobuyuki

    JOURNAL OF HYPERTENSION　34　E326　2016/09

    DOI： 10.1097/01.hjh.0000500812.17722.74 　

    ISSN： 0263-6352

  55. PIVOTAL ROLE OF HEME OXYGENASE IN AMELIORATION BY NICOTINAMIDE OF FETAL GROWTH RESTRICTION ASSOCIATED WITH PREECLAMPSIA

    Nakada Hironobu, Fushima Tomofumi, Sekimoto Akiyo, Oe Yuji, Sato Emiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

    JOURNAL OF HYPERTENSION　34　E236　2016/09

    DOI： 10.1097/01.hjh.0000500524.43340.2b 　

    ISSN： 0263-6352

  56. NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN MICE

    Fushima Tomofumi, Sekimoto Akiyo, Minato Takahiro, Ito Takuya, Oe Yuji, Kisu Kiyomi, Sato Emiko, Funamoto Kenichi, Kimura Yoshitaka, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

    JOURNAL OF HYPERTENSION　34　E237　2016/09

    DOI： 10.1097/01.hjh.0000500527.66210.66 　

    ISSN： 0263-6352

  57. INHIBITING PROTEASE-ACTIVATED RECEPTOR 2 ALLEVIATED PREECLAMPSIA

    Takahashi Nobuyuki, Ko Mieko, Oe Yuji, Fushima Tomofumi, Sekimoto Akiyo, Sato Emiko, Ito Sadayoshi, Sato Hiroshi

    JOURNAL OF HYPERTENSION　34　E101　2016/09

    DOI： 10.1097/01.hjh.0000500120.73302.2e 　

    ISSN： 0263-6352

  58. APPLICATION OF NOVEL REDUCED UTERINE PERFUSION PRESSURE (RUPP) MODEL OF PREECLAMPSIA IN C57BL/6J MICE

    Sekimoto Akiyo, Fushima Tomofumi, Oe Yuji, Kisu Kiyomi, Sato Emiko, Ito Sadayoshi, Sato Hiroshi, Takahashi Nobuyuki

    JOURNAL OF HYPERTENSION　34　E409　2016/09

    DOI： 10.1097/01.hjh.0000501052.07978.d5 　

    ISSN： 0263-6352

  59. Coagulation Factor Xa and Protease-Activated Receptor 2 as Novel Therapeutic Targets for Diabetic Nephropathy Peer-reviewed

    Yuji Oe, Sakiko Hayashi, Tomofumi Fushima, Emiko Sato, Kiyomi Kisu, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY　36　(8)　1525-1533　2016/08

    DOI： 10.1161/ATVBAHA.116.307883 　

    ISSN： 1079-5642

    eISSN： 1524-4636

  60. Reduced Uterine Perfusion Pressure (RUPP) Model of Preeclampsia in Mice Peer-reviewed

    Tomofumi Fushima, Akiyo Sekimoto, Takahiro Minato, Takuya Ito, Yuji Oe, Kiyomi Kisu, Emiko Sato, Kenichi Funamoto, Toshiyuki Hayase, Yoshitaka Kimura, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    PLOS ONE　11　(5)　e0155426　2016/05

    DOI： 10.1371/journal.pone.0155426 　

    ISSN： 1932-6203

  61. THE ROLE OF COAGULATION FACTOR XA AND PROTEASE ACTIVATED RECEPTORS IN DIABETIC NEPHROPATHY

    Yuji Oe, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

    NEPHROLOGY　19　88-89　2014/05

    ISSN： 1320-5358

  62. THERAPEUTIC EFFECT OF NICOTINAMIDE ON IgA NEPHROPATHY

    Tomofumi Fushima, Yuji Oe, Saki Iwamori, Emiko Sato, Yusuke Suzuki, Yasuhiko Tomino, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

    NEPHROLOGY　19　146　2014/05

    ISSN： 1320-5358

  63. Proliferative glomerulonephritis with monoclonal IgM-κ deposits in chronic lymphocytic leukemia/small lymphocytic leukemia: case report and review of the literature. Peer-reviewed

    Oe Y, Joh K, Sato M, Taguma Y, Onishi Y, Nakayama K, Sato T

    CEN Case Rep　2　(2)　222-227　2013

    DOI： 10.1007/s13730-013-0068-z 　

    More details Close

    A 48-year-old man with chronic lymphocytic leukemia presented with nephrotic syndrome, hematuria, and mild deterioration of renal function. Further analysis using serum immunofixation electrophoresis detected monoclonal immunoglobulin (Ig) M-κ and IgG-κ M-protein. Testing for cryoglobulin in serum was negative. Light microscopy of a renal biopsy specimen showed membranoproliferative glomerulonephritis features with marked mononuclear cell infiltration in the interstitium. On immunofluorescence study, the deposition of IgM heavy chain was predominantly observed with the same distribution of κ light chain, whereas no λ light chain was found. Electron microscopy revealed fine granular deposits in the mesangial, subendothelial, and subepithelial areas, mimicking those observed in the immune complex-mediated glomerulonephritis. These pathological findings were consistent with recently described cases of proliferative glomerulonephritis with monoclonal IgG deposits. Thus, monoclonal IgM deposition can also cause proliferative glomerulonephritis.

  64. kappa I light chain AL amyloidosis presenting with rapidly progressive renal and hepatic failure with unusual renal amyloid distribution Peer-reviewed

    Yuji Oe, Izaya Nakaya, Mayumi Yahata, Okinora Murata, Hiroshi Yaegashi, Tsutomu Sakuma, Hiroshi Sato, Juris J. Liepnieks, Merrill D. Benson, Jun Soma

    CLINICAL NEPHROLOGY　77　(1)　66-70　2012/01

    DOI： 10.5414/CN106804 　

    ISSN： 0301-0430

  65. 腹膜アクセス 悪性高血圧における重度腎機能障害 維持透析導入時期の検討

    木村 朋由, 宮坂 康宣, 佐藤 功造, 石山 勝也, 岩渕 將, 土屋 善慎, 家入 伯夫, 高橋 和也, 佐藤 浩司, 水野 真一, 大江 佑治, 古川 暁子, 奥田 拓史, 阿部 倫明, 佐藤 光博, 宮崎 真理子, 野城 宏夫, 佐藤 寿伸, 田熊 淑男

    腎と透析　71　(別冊 腹膜透析2011)　335-337　2011/09

    Publisher: (株)東京医学社

    ISSN： 0385-2156

    More details Close

    悪性高血圧における重度腎機能障害について、維持透析導入時期から検討した。悪性高血圧に伴う重度腎機能障害症17例を経験し、透析導入時期に関する検討を行った。緊急に透析療法を要したのは6例、3例が維持透析継続、残り3例は透析を離脱できた。治療開始後1〜2週をピークに腎機能が改善する例が多く、維持透析決定・アクセス作製は最低2週の経過をみて行うのが望ましいと考えた。17例中7例に透析アクセス作製も1年以内に維持透析を要したのは3例のみ、2年の経過では離脱した1例が14ヵ月で再導入となったが、残りは2年間安定した腎機能経過であった。MAHA合併の有無が治療反応、腎予後を推測するうえで重要な所見と考えた。

  66. Impact of the Oral Adsorbent AST-120 on Organ-Specific Accumulation of Uremic Toxins: LC-MS/MS and MS Imaging Techniques Peer-reviewed

    Sato E, Saigusa D, Mishima E, Uchida T, Miura D, Morikawa-Ichinose T, Kisu K, Sekimoto A, Saito R, Oe Y, Matsumoto Y, Tomioka Y, Mori T, Takahashi N, Sato H, Abe T, Niwa T, Ito S

    Toxins (Basel)　10　(1)　pii: E19　2011

  67. A Case of gamma 1-Heavy Chain Deposition Disease Successfully Treated with Melphalan and Prednisolone Therapy Peer-reviewed

    Yuji Oe, Izaya Nakaya, Mayumi Yahata, Tsutomu Sakuma, Hiroshi Sato, Jun Soma

    INTERNAL MEDICINE　49　(14)　1411-1415　2010

    DOI： 10.2169/internalmedicine.49.3499 　

    ISSN： 0918-2918

Show all ︎Show first 5

Misc. 44

  1. 慢性腎臓病におけるウレミックトキシンと心血管病・血栓関連マーカーの相関

    大江 佑治, 佐藤 恵美子, 宮崎 真理子, 田中 哲洋

    日本透析医学会雑誌　58　(Suppl.1)　2505-2505　2025/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  2. IgG4関連腎臓病に合併し,急性腎障害から血液透析を要した微小変化型ネフローゼ症候群の一例

    大江 佑治, 石垣 駿, 渡邉 駿, 後藤 佐和子, 菊地 晃一, 吉田 舞, 牧野 塁, 長澤 将, 豊原 敬文, 佐藤 博, 宮崎 真理子, 田中 哲洋

    日本透析医学会雑誌　58　(Suppl.1)　2558-2558　2025/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

    eISSN： 1883-082X

  3. 慢性腎臓病における凝固・補体経路の役割とnicotinamideの治療効果

    金沙織, 大江佑治, 小原拓, 佐藤恵美子, 高橋信行, 田中哲洋

    日本腎臓学会誌(Web)　67　(4)　2025

    ISSN： 1884-0728

  4. AKI to CKD移行に対するダパグリフロジンの腎保護作用:アリストロキア酸腎症の検討

    大江佑治, KIM Young Chul, SIDORENKO S Viktoriya, ZHANG Haiyan, KANOO Sadhana, LOPEZ Natalia, GOODLUCK Helen, CRESPO MASIP Maria, VALLON Volker

    日本腎臓学会誌(Web)　66　(4)　2024

    ISSN： 1884-0728

  5. 分娩時大量出血により発症した妊娠関連血栓性微小血管症(TMA)の一例

    吉田舞, 石塚悠奨, 木之村聡介, 野口雄司, 金沙織, 菊地晃一, 大江佑治, 岡本好司, 豊原敬文, 宮崎真理子, 田中哲洋

    日本腎臓学会誌(Web)　66　(6-E)　2024

    ISSN： 1884-0728

  6. 原発性アルドステロン症加療中に腎血管性高血圧を診断・治療し得た難治性高血圧の一例

    石垣駿, 豊原敬文, 石塚悠奨, 渡邉駿, 菊地晃一, 吉田舞, 牧野塁, 大江佑治, 手塚雄太, 小野美澄, 宮崎真理子, 片桐秀樹, 田中哲洋

    日本腎臓学会誌(Web)　66　(6-E)　2024

    ISSN： 1884-0728

  7. WM/LPL及びAA型アミロイドーシスの治療中にクリプトコッカス髄膜炎を発症した一例

    石塚悠奨, 大江佑治, 木之村聡介, 野口雄司, 金沙織, 菊地晃一, 吉田舞, 長澤将, 豊原敬文, 宮崎真理子, 割田仁, 田中哲洋

    日本腎臓学会誌(Web)　66　(6-E)　2024

    ISSN： 1884-0728

  8. 結節性多発動脈炎による腎障害の治療中に眼窩先端症候群を発症した一例

    石塚悠奨, 大江佑治, 木之村聡介, 野口雄司, 金沙織, 豊原敬文, 宮崎真理子, 光澤志緒, 池田謙輔, 田中哲洋

    日本腎臓学会誌(Web)　66　(6-E)　2024

    ISSN： 1884-0728

  9. 非典型的な臨床経過と腎病理を呈した多発血管炎性肉芽腫症

    木之村聡介, 豊原敬文, 白井剛志, 秋保真穂, 菊地晃一, 牧野塁, 吉田舞, 大江佑治, 岡本好司, 長澤将, 宮崎真理子, 佐藤博, 藤井博司, 田中哲洋

    日本腎臓学会誌(Web)　66　(6-E)　2024

    ISSN： 1884-0728

  10. ウレミックトキシンが凝固線溶系因子発現に及ぼす影響

    大江佑治, 佐藤恵美子, 佐藤博, 宮崎真理子, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌(Web)　63　(4)　2021

    ISSN： 1884-0728

  11. ニコチンアミドは炎症の抑制によりアデニン腎症発生を予防する.

    熊倉慧, 佐藤恵美子, 堰本晃代, 大江佑治, 宮崎真理子, 高橋信行

    日本腎臓学会誌(Web)　62　(4)　2020

    ISSN： 1884-0728

  12. 単球・マクロファージ由来組織因子の慢性腎臓病における役割

    山陰周, 大江佑治, 佐藤恵美子, 堰本晃代, 岡本好司, 宮崎真理子, 佐藤博, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌(Web)　62　(4)　2020

    ISSN： 1884-0728

  13. 内皮型NO合成酵素欠損はCKD関連異所性石灰化を誘導する

    大江佑治, 佐藤恵美子, 宮崎真理子, 岡本好司, 佐藤博, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌(Web)　62　(4)　2020

    ISSN： 1884-0728

  14. 肥満に対するアルドステロンの影響-小腸におけるグルコース吸収の役割-

    白井英和, 内田多恵子, 橋爪大和, 大屋咲子, 堰本晃代, 大江佑治, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集(CD-ROM)　42nd　2019

  15. 血液凝固系に関連した糖尿病性腎症早期診断・薬効マーカー

    佐藤 恵美子, 大江 佑治, 佐藤 博, 伊藤 貞嘉, 高橋 信行

    日本腎臓学会誌　60　(3)　402-402　2018/04

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

  16. 新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの開発

    伊丸岡健太, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　40th　362-362　2017/10/20

    Publisher: (NPO)日本高血圧学会

  17. Reduced Uterine Perfusion Pressure(RUPP)preeclampsia(PE)モデルにおけるマウス系統および術式の検討

    堰本晃代, 堰本晃代, 伏間智史, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　40th　362　2017/10/20

  18. sFlt‐1過剰発現eNOS欠損マウスは重症肝障害と血小板減少症を発症する

    大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　40th　362-362　2017/10/20

    Publisher: (NPO)日本高血圧学会

  19. 新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの開発

    大江佑治, 大江佑治, 伊丸岡健太, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

    日本妊娠高血圧学会雑誌　24　74-74　2017/09

    Publisher: (一社)日本妊娠高血圧学会

    ISSN： 1880-3172

  20. sFlt‐1過剰発現eNOS欠損マウスは重症肝障害と血小板減少症を発症する

    大江佑治, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行, 高橋信行

    日本妊娠高血圧学会雑誌　24　60-60　2017/09

    Publisher: (一社)日本妊娠高血圧学会

    ISSN： 1880-3172

  21. RUPP PEモデルにおけるマウス系統および術式の検討

    堰本晃代, 堰本晃代, 伏間智史, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

    日本妊娠高血圧学会雑誌　24　73　2017/09

    ISSN： 1880-3172

  22. 新規Reduced Uterine Perfusion Pressure(RUPP)PEモデルの開発におけるマウス系統の重要性

    堰本晃代, 伏間智史, 大江佑治, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 高橋信行

    日本腎臓学会誌　59　(3)　304　2017/04/25

    ISSN： 0385-2385

  23. アデニン腎症におけるプロテアーゼ活性化受容体2の役割

    林咲貴子, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌　59　(3)　290　2017/04/25

    ISSN： 0385-2385

  24. 新規全身性エリテマトーデス合併妊娠高血圧腎症モデルマウスの作製

    伊丸岡健太, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌　59　(3)　360-360　2017/04/25

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  25. 妊娠高血圧腎症モデルマウスにおけるプロテアーゼ活性化受容体2の役割

    小畑裕史, 江美恵子, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌　59　(3)　305　2017/04/25

    ISSN： 0385-2385

  26. 上皮‐内皮クロストーク機構の破綻と肝腎障害の新規メカニズム

    大江佑治, 伏間智史, 佐藤恵美子, 佐藤博, 菅原準一, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌　59　(3)　230-230　2017/04/25

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

    eISSN： 1884-0728

  27. ニコチンアミドによるIgA腎症合併妊娠への治療効果

    伏間智史, 堰本晃代, 大江佑治, 佐藤恵美子, 鈴木祐介, 佐藤博, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌　59　(3)　305　2017/04/25

    ISSN： 0385-2385

  28. 慢性腎臓病におけるプロテアーゼ活性化受容体2の役割

    林咲貴子, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

    日本薬学会年会要旨集(CD-ROM)　137th　ROMBUNNO.27I‐am13S　2017

  29. 妊娠高血圧腎症の新規薬物治療

    高橋信行, 高橋信行, 伏間智史, 大柳元, 佐藤恵美子, 佐藤恵美子, 中田宏伸, 大江佑治, 堰本晃代, 堰本晃代, 三枝大輔, 佐藤博, 佐藤博, 伊藤貞嘉, LI Feng, JENNETTE JC, 前田信代, KARUMANCHI Ananth, SMITHIES Oliver

    日本薬学会年会要旨集(CD-ROM)　137th　ROMBUNNO.25F‐pm16　2017

  30. LPS投与妊娠高血圧腎症モデルマウスにおけるプロテアーゼ活性化受容体2の役割

    江美恵子, 小畑裕史, 大江佑治, 大江佑治, 伏間智史, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　39th　325　2016/09/30

  31. C57BL/6Jマウスでの新規Reduced Uterine Perfusion Pressure(RUPP)モデルの開発

    堰本晃代, 堰本晃代, 伏間智史, 大江佑治, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　39th　342　2016/09/30

  32. eNOS欠損糖尿病性腎症モデルマウスにおける血液凝固第Xa因子‐プロテアーゼ活性化受容体2の役割

    大江佑治, 林咲貴子, 伏間智史, 佐藤恵美子, 佐藤恵美子, 金須清美, 佐藤博, 佐藤博, 伊藤貞嘉, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　39th　325　2016/09/30

  33. IgA腎症は妊娠により増悪し,妊娠高血圧腎症の危険因子となる

    伏間智史, 大江佑治, 佐藤恵美子, 佐藤恵美子, 鈴木祐介, 富野康日己, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

    日本高血圧学会総会プログラム・抄録集　39th　342　2016/09/30

  34. ニコチンアミドの妊娠高血圧腎症治療効果におけるヘムオキシゲナーゼの役割

    高橋信行, 高橋信行, 中田宏伸, 伏間智史, 堰本晃代, 堰本晃代, 大江佑治, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉

    日本妊娠高血圧学会雑誌　23　67　2016/09

    ISSN： 1880-3172

  35. C57BL/6Jマウスでの新規Reduced Uterine Perfusion Pressure(RUPP)モデルの開発

    伏間智史, 堰本晃代, 大江佑治, 佐藤恵美子, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 佐藤博, 高橋信行, 高橋信行

    日本妊娠高血圧学会雑誌　23　68　2016/09

    ISSN： 1880-3172

  36. 新規Reduced Uterine Perfusion Pressure(RUPP)マウスモデルの開発

    伏間智史, 堰本晃代, 大江佑治, 佐藤恵美子, 伊藤貞嘉, 佐藤博, 高橋信行

    日本腎臓学会誌　58　(3)　303　2016/05/10

    ISSN： 0385-2385

  37. ニコチンアミドはAsb4欠損マウスの妊娠高血圧腎症,妊娠の維持,およびに胎児生存率を改善する

    高橋信行, 高橋信行, 高橋信行, 伏間智史, LI Feng, 大江佑治, 佐藤恵美子, 佐藤恵美子, 佐藤博, 佐藤博, 伊藤貞嘉

    日本高血圧学会総会プログラム・抄録集　38th　405　2015/10/09

  38. ニコチンアミドはAsb4欠損マウスのPE,妊娠の維持,およびに胎児生存率を改善する

    高橋信行, 伏間智史, LI Feng, 大江佑治, 佐藤恵美子, 佐藤博, 伊藤貞嘉

    日本妊娠高血圧学会雑誌　22　72　2015/08

    ISSN： 1880-3172

  39. IgA腎症は妊娠予後を悪化させ,妊娠はIgA腎症を悪化させる(マウスモデルでの検討)

    伏間智史, 大江佑治, 佐藤恵美子, 鈴木祐介, 富野康日己, 伊藤貞嘉, 佐藤博, 高橋信行

    日本妊娠高血圧学会雑誌　22　73　2015/08

    ISSN： 1880-3172

  40. IgA腎症は妊娠予後を悪化させ,妊娠はIgA腎症を悪化させる(マウスモデルにおける検討)

    伏間智史, 大江佑治, 佐藤恵美子, 鈴木祐介, 富野康日己, 伊藤貞嘉, 佐藤博, 高橋信行

    日本腎臓学会誌　57　(3)　503　2015/04/30

    ISSN： 0385-2385

  41. 糖尿病性腎症におけるプロテアーゼ活性化受容体2(PAR2)の役割

    大江佑治, 佐藤恵美子, 佐藤博, 伊藤貞嘉, 高橋信行

    日本腎臓学会誌　57　(3)　502　2015/04/30

    ISSN： 0385-2385

  42. ニコチン酸アミドのIgA腎症に対する治療効果

    伏間智史, 大江佑治, 岩森紗希, 佐藤恵美子, 鈴木裕介, 富野康日己, 伊藤貞嘉, 佐藤博, 高橋信行

    日本腎臓学会誌　56　(3)　388　2014/05/25

    ISSN： 0385-2385

  43. 腎動脈狭窄症による末期腎不全に対する腎動脈拡張術の可能性

    阿部 倫明, 大江 佑治, 田熊 淑男, 佐藤 寿伸

    日本透析医学会雑誌　44　(Suppl.1)　635-635　2011/05

    Publisher: (一社)日本透析医学会

    ISSN： 1340-3451

  44. ANCA関連腎炎初期寛解導入療法におけるシクロフォスファミドの有効性の検討

    岩渕 將, 中屋 来哉, 土屋 善慎, 柴垣 有吾, 大江 佑治, 八幡 真弓, 佐藤 壽伸, 相馬 淳, 田熊 淑男

    日本腎臓学会誌　53　(3)　442-442　2011/05

    Publisher: (一社)日本腎臓学会

    ISSN： 0385-2385

Show all ︎Show first 5

Books and Other Publications 3

  1. 増刊号 腎代替療法のすべて 【第9章 透析患者の合併症】 5 透析患者の低血圧

    大江佑治, 宮崎真理子

    腎と透析 92 (7), 476-478　2022/06/15

  2. Genetic Background of Preeclampsia. In: Saito, S. (eds) Preeclampsia. Comprehensive Gynecology and Obstetrics.

    Sugawara J., Oe Y., Wagata M.

    Springer　2018

  3. 血液凝固系をターゲットとしたDKDの新規治療の可能性

    高橋信行, 大江佑治

    腎と透析　2018

Research Projects 12

  1. 2025年度鈴木万平糖尿病財団若手研究者調査研究助成

    2026/04 - 2029/03

  2. 山口育英奨学会 令和8年度学術研究助成

    2026/07 -

  3. NAD代謝による組織因子制御と慢性腎臓病血栓症の予防法開発

    大江 佑治

    Offer Organization: 日本学術振興会

    System: 科研費若手研究

    Category: 若手研究

    Institution: 東北大学

    2021/04 - 2026/03

    More details Close

    慢性腎臓病(Chronic Kidney Disease, CKD)で，インドキシル硫酸をはじめとした尿毒素が凝固組織因子を活性化し，血栓症リスクを悪化させる機序が明らかにされたが，その予防法の開発が遅れている．ATPエネルギー産生の補酵素であるニコチンアミドアデニンジヌクレオチド(NAD+)と抗老化因子Sirtuinは様々な生命現象を制御し，CKDの進行や合併症を抑制することが報告されている．本研究は，NAD+-Sirtuin経路の活性化がCKD血栓症予防に有効か明らかにすることを目的とし， 1) NAD+前駆体(NAM, NMN)による治療がCKDモデルマウスの組織因子活性や血栓形成を抑制するか，2) その機序としてSirtuin1が関与するか検証する．NAD＋代謝の活性化というこれまでにない新しいアプローチで，腎不全でも安全に使用可能な血栓症予防法を開発し，CKD患者の予後・QOLを改善する治療基盤を構築する． 本年度は研究初年度にあたり，研究計画に沿って慢性腎臓病モデル（アデニン腎症マウス）を作出した．0.2％アデニン食を2週間投与後に解剖した．血液や尿，腎組織などのサンプルを回収した．血液サンプルを用いてBUNなどの腎機能を評価した．血漿第Ｘａ因子活性を測定した．今後NAM，NMNを投与し，血液凝固活性や腎障害に与える影響を評価する予定である．申請者の海外渡航のため研究を中断した．

  4. 日本腎臓財団 令和6年度 CKD（慢性腎臓病）病態研究助成

    2024 -

  5. 日本糖尿病財団・ノボノルディスクファーマ研究助成

    大江佑治

    2024 -

  6. 2024年度日本イーライリリー株式会社 イノベーション研究助成

    大江佑治

    2024 -

  7. 鈴木万平糖尿病財団 海外留学助成

    2021/09 -

  8. プロテアーゼ活性化受容体2によるオートファジー制御と慢性腎臓病合併心血管病 Competitive

    大江佑治

    System: 科研費若手研究

    2018/04 - 2021/03

  9. 妊娠高血圧腎症における凝固因子及びプロテアーゼ活性化受容体の役割 Competitive

    大江佑治

    Offer Organization: 日本学術振興会

    System: 特別研究員奨励費

    2016/04 - 2019/03

  10. 全身性エリテマトーデス合併妊娠の病態解明と新規治療法の開発 Competitive

    大江佑治

    Offer Organization: 神澤医学研究振興財団

    System: 研究助成金

    2016 -

  11. 腎性貧血、腎性骨症におけるプロテアーゼ活性化受容体2 (PAR2) の役割 Competitive

    大江佑治

    System: 日本腎臓財団研究助成

    2016 -

  12. IgA腎症に対するニコチン酸アミドの効果 Competitive

    大江佑治

    System: 宮城県腎臓協会研究助成金

    2013 -

Show all Show first 5