PD-related peritonitis, especially fungal peritonitis, and peritoneal injuries associated with impairment of the complement system

• Project/Area Number: 15K09288
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nagoya University
• Principal Investigator: Mizuno Masashi 名古屋大学, 医学系研究科, 寄附講座教授 (20303638)
• Co-Investigator(Kenkyū-buntansha): 鈴木 康弘 名古屋大学, 医学系研究科, 寄附講座講師 (20584676) ; 坂田 史子 名古屋大学, 医学系研究科, 特任助教 (20726484) ; 伊藤 恭彦 愛知医科大学, 医学部, 教授 (60402632)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 人工透析学 / 腹膜透析 / 補体活性化 / 補体制御 / 腹膜障害 / 腹膜傷害

Outline of Final Research Achievements

Peritoneal injury is an important factor to prevent long-term peritoneal dialysis (PD), possibly following a progression of encapsulating peritoneal sclerosis (EPS) which has poor prognosis. To clarify the complement (C)-related mechanisms of development of peritoneal injuries, we have approached as an aspect of the C activation system. In the present study, we showed changes of membrane C regulators (CReg)’ expression in peritoneal mesothelium. A C activation product, we showed that sC5b-9, was useful as a surrogate maker to predict prognosis of PD-related peritonitis because peritonitis is another reason of PD withdrawal. We also developed a new peritonitis animal model to investigate mechanisms of EPS.

Research Products

• [Int'l Joint Research] Cardiff University(英国)
• [Journal Article] Complement regulation and kidney diseases: recent knowledge of the double-edged roles of complement activation in nephrology. (2018)
  • Author(s): Mizuno M, Suzuki Y, Ito Y.
  • Journal Title: Clinical Experimental Nephrology Volume: 22 Issue: 1 Pages: 3-14
  • DOI: 10.1007/s10157-017-1405-x
  • Peer Reviewed
• [Journal Article] TGF-β1-VEGF-A pathway induces neoaniogenesis with peritoneal fibrosis in patients undergoing pertoneal dialysis. (2018)
  • Author(s): Kariya T., Nishimura H., Mizuno M., Suzuki Y, Matsukawa Y., Sakata F., Maruyama S., Takei Y., Ito Y.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 314 Issue: 2 Pages: F167-F180
  • DOI: 10.1152/ajprenal.00052.2017
  • Peer Reviewed / Open Access
• [Journal Article] High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients. (2017)
  • Author(s): Mizuno M, Suzuki Y, Higashide K, Sei Y, Iguchi D, Sakata F, Horie M, Maruyama S, Matsuo S, Morgan BP, Ito Y.
  • Journal Title: PLoS One. Volume: 12(1) Issue: 1 Pages: e0169111-e0169111
  • DOI: 10.1371/journal.pone.0169111
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sodium chloride promotes tissue inflammation via osmotic stimuli in sub-total-nephrectomized mice. (2017)
  • Author(s): Sakata F., Ito Y., Mizuno M, Sawai A, Suzuki Y, Tomita T, Tawada M, Tanaka A, Hirayama A, Sagara A, Wada T, Maruyama S, Soga T, Matsuo S, Imai E, Takei Y.
  • Journal Title: Lab Invest Volume: 97(4) Issue: 4 Pages: 432-446
  • DOI: 10.1038/labinvest.2017.4
  • Peer Reviewed / Open Access
• [Journal Article] Complement component 5 promotes lethal thrombosis (2017)
  • Author(s): Tomohiro Mizuno, Kengo Yoshioka, Masashi Mizuno, Mie Shimizu, Fumihiko Nagano, Tomoyuki Okuda, Naotake Tsuboi, Shoichi Maruyama, Tadashi Nagamatsu, Masaki Imai
  • Journal Title: Complement component 5 promotes lethal thrombosis. Volume: 16 Issue: 1 Pages: 42714-42714
  • DOI: 10.1038/srep42714
  • Peer Reviewed / Open Access
• [Journal Article] Peritonitis-induced peritoneal injury models: Review of bacterial and non-bacterial models. (2017)
  • Author(s): Ito Y, Kinashi H, Katsuno T. Suzuki Y, Mizuno M.
  • Journal Title: Renal Replacement Therapy Volume: 3 Issue: 1 Pages: 16-16
  • DOI: 10.1186/s41100-017-0100-4
  • Peer Reviewed
• [Journal Article] Apoptosis inhibitor of macrophage ameliorates fungus-induced peritoneal injury model in mice (2017)
  • Author(s): Tomita T, Arai S, Kitada K, Mizuno M, Suzuki Y, Sakata F, Nakano D, Hiramoto E, Takei Y, Maruyama S, Nishiyama A, Matsuo S, Miyazaki T, Ito Y.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 6450-6450
  • DOI: 10.1038/s41598-017-06824-6
  • Peer Reviewed / Open Access
• [Journal Article] Recent analysis of status and outcomes of peritoneal dialysis (2016)
  • Author(s): Mizuno M., Ito Y, Skata F, Saka Y, Hiramatsu T, Tamai H, Mizutani M, Naruse T, Ohashi N, Kasuga H, Shimizu H, Kurata H, Kurata K, Suzuki S, Kido S, Tsuruta Y, Matsuoka T, Horie M, Naruyama S, Matsuo S.
  • Journal Title: Clin Exp Nephrol Volume: in press Issue: 6 Pages: 961-971
  • DOI: 10.1007/s10157-016-1249-9
  • Peer Reviewed
• [Journal Article] Depression of complement regulatory factors in rat and human renal grafts is associated with the pregress of acute T-cell medicated rejection. (2016)
  • Author(s): Yamanaka K, Kakuta Y, Miyagawa S, Nakazawa S, Kato T, Abe T, Imamura R, Okumi M, Maeda A, Okuyama H, Mizuno M, Nonomura N.
  • Journal Title: PlosOne. Volume: 11 Issue: 2 Pages: e0148881-e0148881
  • DOI: 10.1371/journal.pone.0148881
  • Peer Reviewed / Open Access
• [Journal Article] Vascular endothelial cell injury is an important factor in the development of encapsulating peritoneal sclerosis in long-term peritoneal dialysis patients. (2016)
  • Author(s): Tawada M, Ito Y, Hamada C, Honda K, Mizuno M, Suzuki Y, Sakata F, Terabayashi T, Matsukawa Y, Maruyama S, Imai E, Matsuo S, Takei Y.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0154644-e0154644
  • DOI: 10.1371/journal.pone.0154644
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Recent analysis of status and outcome of peritoneal dialysis in the Tokai area of Japan: the second report of the Tokai peritoenal dialysis registry. (2016)
  • Author(s): Mizuno M, Ito Y, Suzuki Y, Sakata F, Saka Y, Hiramatsu T, Tamai H, Mizutani M, Naruse T, Ohashi N, Kasuga H, Shimizu H, Kurata H, Kurata K, Suzuki S, Kido S, Tsuruta Y, Matsuoka T, Horie M, Maruyama S, Matsuo S.
  • Journal Title: Clin Exp Nephrol Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Expression of membrane complement regulators, CD46, CD55 and CD59, in mesothelial cells of patients on peritoneal dialysis therapy. (2015)
  • Author(s): Sei Y, Mizuno M, Suzuki Y, Imai M, Higashide K, Harris CL, Sakata F, Iguchi D, Fujiwara M, Kodera Y, Maruyama S, Matsuo S, Ito Y
  • Journal Title: Molecular Immunology Volume: 153 Issue: 2 Pages: 302-309
  • DOI: 10.1016/j.molimm.2015.02.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Calcified amorphous tumor in the left atrium of a patient on long-term peritoneal dialysis. (2015)
  • Author(s): Tanaka A, Mizuno M, Suzuki Y, Oshima H, Sakata F, Ishikawa H, Tsukushi S, Ito Y.
  • Journal Title: Inten Med Volume: 54 Pages: 481-485
  • NAID: 130004724006
• [Journal Article] Successful Treatment of <i>Cryptococcus laurentii</i> Peritonitis in a Patient on Peritoneal Dialysis (2015)
  • Author(s): Asano M, Mizutani M, Nagahara Y, Inagaki K, Kariya T, Masamoto D, Urai M, Kaneko Y, Ohno H, Miyazaki Y, Mizuno M, Ito Y.
  • Journal Title: Internal Medicine Volume: 54 Issue: 8 Pages: 941-944
  • DOI: 10.2169/internalmedicine.54.3586
  • NAID: 130005065248
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Open Access
• [Journal Article] The efficacy of tolvaptan as a diuretic for chronic kidney disease patients. (2015)
  • Author(s): Tanaka A, Katsuno T, Ozaki T, Sakata F, Kato N, Suzuki Y, Kosugi T, Kato S, Tsuboi N, Sato W, Yasuda Y, Mizuno M, Ito Y, Matsuo S, Maruyama S.
  • Journal Title: Acta Cardiol. Volume: 70 Pages: 217-223
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury (2015)
  • Author(s): Terabayashi T, Ito Y, Mizuno M, Suzuki Y, Kinashi H, Sakata F, Tomita T, Iguchi D, Tawada M, Nishio R, Maruyama S, Imai E, Matsuo S, Takei Y.
  • Journal Title: Laboratory Investigation Volume: 95(9) Issue: 9 Pages: 1029-1043
  • DOI: 10.1038/labinvest.2015.87
  • Peer Reviewed
• [Presentation] Expression of membrane complement regulators in patients dependent on peritoneal dialysis therapy and regulation of complement activation in peritoneal dialysate. (2017)
  • Author(s): Mizuno M, Sei Y, Kobayashi K, Shigemoto E, Suzuki Y, Sakata F, Imai M, Maruyama S, Matsuo S, Ito Y.
  • Organizer: The 8th APCM-ISPD
  • Place of Presentation: Guangzhou, China
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] Expression of membrane complement regulators in patients dependent on peritoneal dialysis therapy and regulation of complement activation in peritoneal dialysate. (2017)
  • Author(s): Mizuno M., Sei Y, Kobayashi K, Shigemoto E, Suzuki Y, Sakata F, Imai M, Maruyama S, Matsuo S, Ito Y.
  • Organizer: APCM-ISPD 2017
  • Int'l Joint Research
• [Presentation] VEGF-D plays a suitable role in the development of lymphangenesis in methylglyoxal-induced peritoneal injury. (2017)
  • Author(s): Sun T, Ito Y, Mizuno M, Suzuki Y, Sakata F, Terabayashi T, Tomita T, Maruyama S.
  • Organizer: APCM-ISPD 2017
  • Int'l Joint Research
• [Presentation] Neutral peritoneal dialysis solutions reduce morphological damages in the patients with long-term peritoneal membrane treatment. (2017)
  • Author(s): Ito Y, Tawada M, Hamada C, Mizuno M, Suzuki Y, Sakata F, Maruyama S.
  • Organizer: APCM-ISPD 2017
  • Int'l Joint Research
• [Presentation] Peritoneal eosinophils increases during induction of peritoneal dialysis and may be related to production of C3a in peritoneal dialysate. (2017)
  • Author(s): Shigemoto E, Mizuno M, Kobayashi K, Iguchi D, Sakata F, Suzuki Y, Maruyama S, Ito Y.
  • Organizer: The 15th European Meeting on Complement in Human Disease.
  • Int'l Joint Research
• [Presentation] ミニシンポジウム「補体関連疾患の新展開～補体の関与と新規治療戦略の可能性～」C3腎症の最近の診断と治療についての話題. (2017)
  • Author(s): 水野正司
  • Organizer: 第54回日本補体学会学術集会
  • Invited
• [Presentation] シンポジウム2早期離脱 腹膜透析からの早期離脱と腹膜炎. (2017)
  • Author(s): 水野正司、坂田史子、鬼無洋、鈴木康弘、伊藤恭彦
  • Organizer: 第22回 日本腹膜透析学会
  • Invited
• [Presentation] 腹膜透析導入時における排液中好酸球数の解析. (2016)
  • Author(s): 重本絵美、水野正司、井口大旗、小林和磨、坂田史子、鈴木康弘、丸山彰一、伊藤恭彦
  • Organizer: 第22回 日本腹膜透析学会
  • Place of Presentation: 札幌プリンスホテル国際館パミール（北海道札幌市）
  • Year and Date: 2016-09-24
• [Presentation] Comparison of prevalence of peritoneal dialysis (PD) therapy in end-stage renal disease (ESRD) patients from 2010 to 2012 in the Tokai area of Japan. (2016)
  • Author(s): Mizuno M, Ito Y, Suzuki Y, Saka Y, Hiramatsu T, Tamai H, Mizutani M, Naruse T, Ohashi N, Kasuga H, Shimizu H, Kurata H, Kurata K, Suzuki S, Matsuoka T, Horie M, Maruyama S, Matsuo S and Tokai PD registry research group.
  • Organizer: The 34th Congress of the International Society of Blood Purification
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2016-09-08
  • Int'l Joint Research
• [Presentation] Complement activation plays important roles to develop severe peritoneal injuries and encapsular peritoneal sclerosis-like changes in rat fungal peritonitis models and effects of a C5a antagonist, AcPepA, can prevent peritoneal injuries. (2016)
  • Author(s): Mizuno M, Iguchi D, Shigemoto E, Kobayashi K, Sakata F, Suzuki Y, Okada A, Okada H, Matsuo S, Ito Y.
  • Organizer: The 34th Congress of the International Society of Blood Purification
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2016-09-08
  • Int'l Joint Research
• [Presentation] Therapeutic effects of a C5a antagonist, AcPepA, for severe peritoneal injuries associated with fungal infection in a rat model. (2016)
  • Author(s): Mizuno M, Iguchi D, Shigemoto E, Kobayashi K, Sakata F, Suzuki Y, Okada A, Okada H, Matsuo S, Ito Y.
  • Organizer: The XXVIth International Complement Workshop
  • Place of Presentation: ホテル日航金沢（石川県金沢市）
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] C5 promotes Histone-induced lethal thromboembolism. (2016)
  • Author(s): Mizuno T, Yoshioka K, Mizuno M, Tsuboi N, Maruyama S, Nagamatsu T, Imai M
  • Organizer: The XXVIth International Complement Workshop
  • Place of Presentation: ホテル日航金沢（石川県金沢市）
  • Year and Date: 2016-09-04
  • Int'l Joint Research
• [Presentation] 非嚢性腹膜硬化症様ラット真菌性腹膜炎モデルの作成と補体関与の検討. (2016)
  • Author(s): 井口大旗、水野正司、坂田史子、鈴木康弘、伊藤恭彦、丸山彰一、松尾清一
  • Organizer: 第61回日本透析学会学術集会
  • Place of Presentation: 大阪リーガロイヤルホテル（大阪府大阪市）
  • Year and Date: 2016-06-10
• [Presentation] Complement promote to releasing transglutaminase 2 from cytoplasm. (2016)
  • Author(s): 3.Hara K, Mizuno T, Takahashi K, Mizuno M, Kato A, Onouchi T, Tsutsumi Y, Tatsukawa H, Nagamatsu T, Hitonmi K, Yuzawa Y.
  • Organizer: The XXVIth International Complement Workshop
  • Place of Presentation: ホテル日航金沢（石川県金沢市）
  • Int'l Joint Research
• [Presentation] Sodium Chloride Promotes Tissue Inflammation via Osmotic Stimuli in Subtotal. (2015)
  • Author(s): F Sakata, Y Ito, M Mizuno, Y Suzuki, T Terabayashi, T Tomita, M Tawada, S Maruyama, E Imai, Y Takei, S Matsuo.
  • Organizer: ASN Kidney Week 2015
  • Place of Presentation: San Diego Convention Center(San Diego,USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Vascular Endothelial Cell Damage Is an Important Factor in the Development. (2015)
  • Author(s): M Tawada, Y Ito, C Hamada, K Honda, M Mizuno, Y Suzuki, F Sakata, S Maruyama, Y Takei, S Matsuo.
  • Organizer: ASN Kidney Week 2015
  • Place of Presentation: San Diego Convention Center(San Diego,USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] 18.被嚢性変化を伴うラット腹膜炎モデルの作成とAcPepA効果の検討 (2015)
  • Author(s): 井口大旗、水野正司、重本絵実、坂田史子、鈴木康弘、岡田亜蘭、岡田秀親、丸山彰一、松尾清一、伊藤恭彦
  • Organizer: 第52回日本補体学会学術集会
  • Place of Presentation: 名古屋大学(愛知県名古屋市)
  • Year and Date: 2015-08-21
• [Presentation] Development of encapsular peritoneal sclerosis(EPS)-like peritonitis in rat and complement activation (2015)
  • Author(s): Daiki iguchi, Masashi Mizuno, Emi Shigemoto, Fumiko Sakata, Yasuhiro Suzuki, Alan Okada, Hidechika Okada, Shoichi Maruyama, Seiichi Matsuo
  • Organizer: he 15th European Meeting on Complement in Human Disease
  • Place of Presentation: Uppsala Konsert & Kongress（Uppsala,Sweden）
  • Year and Date: 2015-06-27
  • Int'l Joint Research
• [Presentation] 腹膜透析患者の腹膜中皮細胞における膜補体制御因子の発現 (2015)
  • Author(s): 水野正司、清祐美、井口大旗、東出慶子、坂田史子、鈴木康弘、今井優樹、松尾清一、伊藤恭彦
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] メサンギウム増殖性腎炎の病因解明に向けた補体活性化とトランスグルタミナーゼ2の関連について (2015)
  • Author(s): 水野智博、高橋和男、尾之内高慶、水野正司、秋山真一、丸山彰一、辰川英樹、人見清隆、永松正、湯澤由紀夫
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 被嚢性腹膜硬化症様の高度な腸管癒着を伴うラット腹膜炎モデルの作成と補体活性化の関与の検討 (2015)
  • Author(s): 井口大旗、水野正司、重本絵実、坂田史子、鈴木康弘、丸山彰一、松尾清一、伊藤恭彦
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05
• [Presentation] 11.2010～12年の東海地区15施設の腹膜透析調査（東海PDレジストリ2）における腹膜炎発生に関する報告） (2015)
  • Author(s): 水野正司、伊藤恭彦、鈴木康弘、坂田史子、坂洋佑、平松武幸、玉井宏史、水谷真、成瀬友彦、大橋徳巳、春日弘毅、志水英明、倉田久嗣、倉田圭、鈴木聡、鶴田吉和、丸山彰一、松尾清一
  • Organizer: 第58回日本腎臓学会学術総会
  • Place of Presentation: 国際会議場（愛知県名古屋市）
  • Year and Date: 2015-06-05