Faculty Profiles - MIZUNO, Masashi

A case of C3 glomerulopathy with nephritis-associated plasmin receptor positivity without a history of streptococcal infection Reviewed International journal

Asano, M; Oda, T; Mizuno, M

CEN CASE REPORTS Vol. 11 ( 2 ) page： 259 - 264 2022.5

Expression of a Crry/p65 is reduced in acute lung injury induced by extracellular histones. Reviewed International journal

Fumihiko Nagano, Tomohiro Mizuno, Masaki Imai, Kazuo Takahashi, Naotake Tsuboi, Shoichi Maruyama, Masashi Mizuno

FEBS open bio Vol. 12 ( 1 ) page： 192 - 202 2022.1

Language：English Publishing type：Research paper (scientific journal)

Acute lung injury (ALI) occurs in patients with severe sepsis and has a mortality rate of 40%-60%. Severe sepsis promotes the release of histones from dying cells, which can induce platelet aggregation, activate coagulation and cause endothelial cell (EC) death. We previously reported that the expression of membrane complement receptor type 1-related gene Y (Crry)/p65, which plays a principal role in defence against abnormal activation of complement in the blood, is reduced in response to peritoneal mesothelial cell injury, and we hence hypothesized that a similar mechanism occurs in pulmonary ECs. In this study, we examined the role of Crry/p65 in histone-mediated ALI using an experimental animal model. In ALI model mice, exposure to extracellular histones induces lung injury and results in a decrease in Crry/p65 expression. The levels of lactic acid dehydrogenase (LDH), a marker of cell damage, were significantly increased in the serum of ALI model compared with vehicle mice. The significant inverse correlation between the expression of Crry/p65 and LDH levels in plasma revealed an association between Crry/p65 expression and cell damage. The levels of complement component 3a (C3a) were also significantly increased in the serum of the ALI model compared with vehicle mice. Notably, a C3a receptor antagonist ameliorated lung injury induced by histones. We hypothesize that extracellular histones induce complement activation via down-regulation of Crry/p65 and that C3a might serve as a therapeutic target for the treatment of ALI.

DOI： 10.1002/2211-5463.13322

Complement activation and C3 glomerulopathy

A novel model mouse for type 2 diabetes mellitus with early onset and persistent hyperglycemia Reviewed International journal

Ohno Tamio, Miyasaka Yuki, Yoshida Kanta, Kobayashi Misato, Horio Fumihiko, Yokoi Norihide, Mizuno Masashi, Ikegami Hiroshi

Experimental Animals Vol. 71 ( 4 ) page： 510 - 518 2022

Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Association for Laboratory Animal Science

Various mouse models of type 2 diabetes have been established, but few of these show early onset and persistent hyperglycemia. We have established a congenic mouse strain (NSY.B6-Tyr+,Ay) in which a spontaneous mutation of the agouti yellow (Ay) gene, which causes obesity by hyperphagia, was introduced into the NSY strain, which shows increased glucose intolerance with age. This strain has been maintained as a segregating inbred strain by mating obese yellow (Ay/a) males with normal black (a/a) females. All yellow males showed marked obesity and hyperglycemia (mean blood glucose level >400 mg/dl) from 10 to 24 weeks of age. The yellow males also showed glucose intolerance and insulin resistance. They provide a potentially valuable model mouse for research into type 2 diabetes, hyperlipidemia, fatty liver, and renal glomerular complications. Yellow female mice also showed marked obesity, but the incidence of diabetes and the severity of various pathological conditions were milder than in yellow males. None of the black mice showed hyperglycemia in either sex. NSY.B6-Tyr+,Ay strain has good fertility and does not display inter-male aggression, making them useful as a new model for type 2 diabetes with early onset and persistent hyperglycemia.

DOI： 10.1538/expanim.22-0061

Mizuno Masashi

Japanese journal of pediatric nephrology Vol. 35 ( 1 ) page： 5 - 12 2022

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society for Pediatric Nephrology

The classical roles of the complement (C) system are known to contribute in part to innate host immunity. In addition, bridging roles of the C system to adaptive immunity were found in the late 21st Century. Since anti-C agents such as C1-inhibitor and anti-C5 antibodies have started to be used in clinical practice during recent decades, the C system has become more familiar to clinicians. Analyses of aspects of the C system are now starting to clarify pathological mechanisms related to the C system and anti-C agents are under development. In the field of nephrology, unexpected C activation has been associated with the incidence, development and/or progression of glomerular and interstitial injuries. Moreover, atypical hematolytic uremic syndrome and C3 nephropathy were referred to as C-associated diseases. However, issues associated with C3 glomerulopathy, its pathogenesis, etiology and therapeutic approaches remain unclear. This mini-review provides a short summary and discussion of renal pathogeneses associated with the C system and its dysregulation, with particular focus on recent insights into C3 glomerulopathy.

DOI： 10.3165/jjpn.rv.2022.0002

CiNii Research

Low-GDP, pH-neutral solutions preserve peritoneal endothelial glycocalyx during long-term peritoneal dialysis. Reviewed International coauthorship International journal

Naoya Sugiyama, Mitsuhiro Tawada, Ting Sun, Yasuhiro Suzuki, Hiroshi Kinashi, Makoto Yamaguchi, Takayuki Katsuno, Jan Aten, Carmen A Vlahu, Toin H van Kuppevelt, Yoshifumi Takei, Takuji Ishimoto, Shoichi Maruyama, Masashi Mizuno, Yasuhiko Ito

Clinical and experimental nephrology Vol. 25 ( 9 ) page： 1035 - 1046 2021.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: During peritoneal dialysis (PD), solute transport and ultrafiltration are mainly achieved by the peritoneal blood vasculature. Glycocalyx lies on the surface of endothelial cells and plays a role in vascular permeability. Low-glucose degradation product (GDP), pH-neutral PD solutions reportedly offer higher biocompatibility and lead to less peritoneal injury. However, the effects on the vasculature have not been clarified. METHODS: Peritoneal tissues from 11 patients treated with conventional acidic solutions (acidic group) and 11 patients treated with low-GDP, pH-neutral solutions (neutral group) were examined. Control tissues were acquired from 5 healthy donors of kidney transplants (control group). CD31 and ratio of luminal diameter to vessel diameter (L/V ratio) were evaluated to identify endothelial cells and vasculopathy, respectively. Immunostaining for heparan sulfate (HS) domains and Ulex europaeus agglutinin-1 (UEA-1) binding was performed to assess sulfated glycosaminoglycans and the fucose-containing sugar chain of glycocalyx. RESULTS: Compared with the acidic group, the neutral group showed higher CD31 positivity. L/V ratio was significantly higher in the neutral group, suggesting less progression of vasculopathy. Both HS expression and UEA-1 binding were higher in the neutral group, whereas HS expression was markedly more preserved than UEA-1 binding in the acidic group. In vessels with low L/V ratio, which were found only in the acidic group, HS expression and UEA-1 binding were diminished, suggesting a loss of glycocalyx. CONCLUSION: Peritoneal endothelial glycocalyx was more preserved in patients treated with low-GDP, pH-neutral solution. The use of low-GDP, pH-neutral solutions could help to protect peritoneal vascular structures and functions.

DOI： 10.1007/s10157-021-02078-9

生体腎移植術を安全に施行できた著明な血小板減少症を合併するEpstein症候群の一例

安田宜成, 岡崎雅樹, 菱田学, 田中章仁, 斎藤尚二, 加藤規利, 鈴木康弘, 小杉智規, 水野正司, 藤田高史, 加藤真史, 藤元昭一, 此元隆雄, 丸山彰一

移植 Vol. 56 ( 総会臨時 ) page： P1 - 50 2021.9

Vasculopathy plays an important role during the development and relapse of encapsulating peritoneal sclerosis with conventional peritoneal dialysis solutions. Reviewed International coauthorship International journal

Mitsuhiro Tawada, Yasuhiko Ito, Masataka Banshodani, Masahiro Yamashita, Sadanori Shintaku, Ting Sun, Yasuhiro Suzuki, Hiroshi Kinashi, Yoko Kubo, Masahiko Ando, Makoto Yamaguchi, Takayuki Katsuno, Masashi Mizuno, Hideki Kawanishi

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Vol. 36 ( 8 ) page： 1519 - 1526 2021.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an uncommon but life-threatening complication of peritoneal dialysis (PD) therapy. The causative factors of EPS remain unclear. Pathological studies of the peritoneum affected by EPS and relationships with clinical factors including PD solutions remain lacking. The objective of this study was to examine peritoneal samples from EPS patients and to identify the associations of peritoneal pathology with different clinical factors. METHODS: Peritoneal specimens were obtained at the time of surgical enterolysis in Tsuchiya General Hospital from 1993 to 2016. A total of 223 PD patients were enrolled and analyzed. Tissues were fixed with formalin and processed with hematoxylin and eosin and Masson's trichrome staining, as well as immunohistochemical staining for CD31 and CD68. RESULTS: Evaluations could be made in 174 patients who received surgical enterolysis. Conventional or pH-neutral low-glucose degradation product PD solutions were utilized during PD treatment. The conventional PD solution group showed less angiogenesis (P = 0.013) but more severe vasculopathy, in the form of a lower ratio of luminal diameter to vessel diameter (L/V ratio) (P < 0.001) in association with longer PD treatment. Multivariate Cox proportional hazard models revealed that L/V ratio (per 0.1 increase, hazard ratio = 0.88, 95% confidence interval 0.77-0.99, P = 0.047) was significantly associated with a lower incidence of EPS relapse. In contrast, most of the cases in the pH-neutral solution group showed milder vasculopathy. CONCLUSIONS: The pathology of EPS differed between conventional and pH-neutral solution groups. Vasculopathy was related to the development and relapse of EPS in the conventional solution group.

DOI： 10.1093/ndt/gfaa073

A case of temporary metastatic pulmonary calcification in a patient with hyperparathyroidism on peritoneal dialysis. Reviewed International journal

Kota Kawase, Kimiaki Takagi, Masashi Mizuno, Masanobu Horie

Clinical nephrology Vol. 95 ( 3 ) page： 161 - 165 2021.3

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Ectopic calcification is associated with secondary hyperparathyroidism (HPT) in patients with end-stage renal failure (ESRD). Metastatic pulmonary calcification (MPC) is another rare type of ectopic calcification, and there are a few reports on MPC in dialysis patients. CASE PRESENTATION: We report the case of a 52-year-old woman admitted with general fatigue and appetite loss, who was on peritoneal dialysis (PD) for 7 years. Although she was initially suspected of having secondary HPT due to ESRD, we finally diagnosed ectopic HPT that was caused by a cystic mass behind her thyroid gland overlapping with secondary HPT. We carefully observed her under conservative therapy because she refused surgery. On admission, she was diagnosed as having MPC because she had ground-glass-like opacification in her lung fields on high-resolution computed tomography scan, which was caused by a parathyroid tumor complicated by secondary HPT associated with ESRD. After she began intravenous injection of etelcalcetide hydrochloride, serum calcium, and intact parathyroid hormone (iPTH), values were adjusted, and the opacification disappeared. CONCLUSION: In a patient on PD, this is the first case of MPC that developed due to acute hypercalcemia, hyperphosphatemia, and dehydration and in which the ectopic pulmonary calcification clearly decreased with optimization of iPTH.

DOI： 10.5414/CN110337

腎障害への補体の関与 Invited

金恒秀, 水野正司

腎臓内科 Vol. 13 ( 3 ) page： 361 - 367 2021.3

Oral Antibiotics are Effective for Preventing Colonoscopy-associated Peritonitis as a Preemptive Therapy in Patients on Peritoneal Dialysis Reviewed International journal

Suzuki Yasuhiro, Mizuno Masashi, Kojima Hiroshi, Sato Yuka, Kim Hangsoo, Kinashi Hiroshi, Katsuno Takayuki, Ishimoto Takuji, Maruyama Shoichi, Ito Yasuhiko

Internal Medicine Vol. 60 ( 3 ) page： 353 - 356 2021

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Internal Medicine

Objective In patients on peritoneal dialysis (PD), it was reported that colonoscopy, but not upper gastrointestinal endoscopy, could cause peritonitis as a complication. A guideline of the International Society for Peritoneal Dialysis recommends preemptive intravenous antibiotics administration of ampicillin and aminoglycoside with or without metronidazole, to prevent colonoscopy-associated peritonitis. In this study, we retrospectively evaluated the effects of preemptive antibiotics therapy by oral administration instead of intravenous administration. Methods We investigated the incidence of colonoscopy-associated peritonitis in a single center. In 170 patients undergoing PD between January 2010 and December 2019, 50 colonoscopies were performed, including 49 with oral administration of amoxicillin and ciprofloxacin and/or metronidazole as preemptive therapy 1 hour before the colonoscopy procedure, and 1 without. Results We observed no incidence of colonoscopy-associated peritonitis. Conclusion Generally, oral administration of preemptive antibiotics is less painful and more convenient than intravenous administration, especially in outpatient procedures, such as a colonoscopy. Our results suggest that oral antibiotic administration might be effective for preventing colonoscopy-associated peritonitis in PD patients.

DOI： 10.2169/internalmedicine.5092-20

Refractory Hypotension Caused by Selenium Deficiency in a Patient on Peritoneal Dialysis Reviewed International journal

Ryuge Akihiro, Kim Hangsoo, Suzuki Yasuhiro, Okazaki Masaki, Kojima Hiroshi, Saito Shoji, Kato Noritoshi, Ishimoto Takuji, Kosugi Tomoki, Maruyama Shoichi, Mizuno Masashi

Internal Medicine Vol. 60 ( 15 ) page： 2461 - 2464 2021

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Internal Medicine

Selenium is essential for human health; its deficiency leads to cardiac dysfunction. We herein report a 79-year-old man on peritoneal dialysis who presented with refractory hypotension caused by selenium deficiency. He was admitted to our hospital with bacterial pneumonia and hypotension and abnormal electrocardiogram (ECG) findings. Despite improvement of pneumonia, his hypotension continued, and intravenous noradrenalin could not be discontinued. His serum selenium level was extremely low, and he was started on intravenous selenium. His hypotension and ECG findings gradually improved, and noradrenalin was discontinued. Physicians should consider selenium deficiency when patients on peritoneal dialysis show refractory hypotension.

DOI： 10.2169/internalmedicine.6632-20

Impact on survival of urgent dialysis initiation in patients with end-stage renal disease: a case-control study. Reviewed International journal

Kimiaki Takagi, Masashi Mizuno, Kota Kawase, Kenichi Minoshima, Masayoshi Yamaha, Masanobu Horie

Clinical and experimental nephrology Vol. 24 ( 12 ) page： 1154 - 1161 2020.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Outcomes of patients with end-stage renal disease at urgent dialysis initiation are varied, but evidence of their long-term prognosis is limited. We aimed to characterize patients undergoing urgent dialysis initiation and analyse its effect on survival outcome. METHODS: We retrospectively identified 208 patients who began haemodialysis from 1 January 2012 to 31 December 2018 at our hospital. In this observational case-control study, the case group comprised patients starting urgent dialysis, and the control group comprised patients starting planned dialysis. We analysed laboratory data, sex, age, smoking history, comorbidities and presence of vascular access and nephrology care that potentially affected the outcome. Data were analysed with Kaplan-Meier curves of early and late period (3 years after dialysis initiation) survival and log-rank tests and with Cox regression analysis. RESULTS: Median age (range) at dialysis initiation was 73 (28-90) years, with 50 (24%) patients in the urgent initiation group. Five (10%) patients in this group had vascular access at dialysis initiation, whereas 21 (42%) had not received adequate pre-dialysis nephrology care. The estimated median overall survival rates of the urgent group and planned initiation group were 42 months and not reached, respectively (P = 0.0011). Multivariable analysis found urgent dialysis initiation to be an independent risk factor for survival (HR 2.36; 95% CI 1.36-4.00; P = 0.02). Survival was not significantly different between the groups for patients who continued chronic dialysis for > 3 years from dialysis initiation (P = 0.1339). CONCLUSION: The prognosis of patients starting dialysis in an urgent condition was poor compared with those who started planned dialysis.

DOI： 10.1007/s10157-020-01931-7

遺伝性血管性浮腫(Hereditary angioedema:HAE)診療ガイドライン改訂2019年版 Reviewed

堀内孝彦, 大澤勲, 今井優樹, 大谷克城, 関根英治, 塚本浩, 中尾実樹, 西村純一, 水野正司, 村上良子, 山本哲郎, 木下タロウ, 大井洋之, 井上徳光, 若宮伸隆, 野々山恵章, 一般社団法人日本補体学会, 厚生労働省難治性疾患等政策研究事業「原発性免疫不全症候群の診断基準・重症度分類および診療ガイドラインの確立に関する研究」研究班

補体 Vol. 57 ( 1 ) page： 3 - 22 2020.12

補体活性異常とC3腎症 Invited Reviewed

水野正司

日本小児腎臓病学会雑誌 Vol. 33 ( 1Suppl. ) page： 51 - 51 2020.12

ANALYSIS OF FREQUENCY AND KINDS OF ALARM HISTORIES OF HOME PD SYSTEM KAGUYA DURING THE INTRODUCTION: PERIOD IN A SINGLE CENTRE

Hiramatsu Tetsuaki, Mizuno Masasi, Suzuki Yasuhiro, Nomori Sumiyo, Suzuki Masafumi, Shiga Yoshiko, Sato Yuka, Nakamura Tomohiro, Ishimoto Takuji, Kosugi Tomoki, Maruyama Shoichi, Koyama Tomio

NEPHROLOGY Vol. 25 page： 77 - 78 2020.10

CASES OF ACUTE APPENDICITIS IN PATIENTS ON PERITONEAL DIALYSIS (PD) IN A SINGLE CENTRE DURING 15 YEARS

Mizuno, M; Suzuki, Y; Kojima, H; Sato, Y; Kinashi, H; Katsuno, T; Maruyama, S; Ito, Y

NEPHROLOGY Vol. 25 page： 82 - 82 2020.10

The effectiveness and safety of computed tomographic peritoneography and video-assisted thoracic surgery for hydrothorax in peritoneal dialysis patients: A retrospective cohort study in Japan. Reviewed International coauthorship International journal

Naoya Matsuoka, Makoto Yamaguchi, Akimasa Asai, Keisuke Kamiya, Hiroshi Kinashi, Takayuki Katsuno, Takaaki Kobayashi, Hirofumi Tamai, Takatoshi Morinaga, Takaaki Obayashi, Kichio Nakabayashi, Shigehisa Koide, Michimasa Nakanishi, Katsushi Koyama, Yasuhiro Suzuki, Takuji Ishimoto, Masashi Mizuno, Yasuhiko Ito

PloS one Vol. 15 ( 9 ) page： e0238602 2020.9

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Albeit uncommon, hydrothorax is an important complication of peritoneal dialysis (PD). Due to paucity of evidence for optimal treatment, this study aimed to evaluate the effectiveness and safety of computed tomographic (CT) peritoneography and surgical intervention involving video-assisted thoracic surgery (VATS) for hydrothorax in a retrospective cohort of patients who underwent PD in Japan. METHODS: Of the 982 patients who underwent PD from six centers in Japan between 2007 and 2019, 25 (2.5%) with diagnosed hydrothorax were enrolled in this study. PD withdrawal rates were compared between patients who underwent VATS for diaphragm repair (surgical group) and those who did not (non-surgical group) using the Kaplan-Meier method and log-rank test. RESULTS: The surgical and non-surgical groups comprised a total of 11 (44%) and 14 (56%) patients, respectively. Following hydrothorax diagnosis by thoracentesis and detection of penetrated sites on the diaphragm using CT peritoneography, VATS was performed at a median time of 31 days (interquartile range [IQR], 20-96 days). During follow-up (median, 26 months; IQR, 10-51 months), 9 (64.3%) and 2 (18.2%) patients in the non-surgical and surgical groups, respectively, withdrew from PD (P = 0.021). There were no surgery-related complications or hydrothorax relapse in the surgical group. CONCLUSIONS: This study demonstrated the effectiveness and safety of CT peritoneography and VATS for hydrothorax. This approach may be useful in hydrothorax cases to avoid early drop out of PD and continue PD in the long term. Further studies are warranted to confirm these results.

DOI： 10.1371/journal.pone.0238602