Faculty Profiles - MIZUNO, Masashi

Nutritional Assessment and Nutrient Supplement in Patients with Chronic Kidney Disease

Video-assisted thoracoscopic surgery for pleuroperitoneal communication International journal

Tsubouchi, H; Nakamura, S; Fukui, T; Kadomatsu, Y; Ueno, H; Ozeki, N; Fukumoto, K; Mizuno, M; Chen-Yoshikawa, TF

ASIAN JOURNAL OF ENDOSCOPIC SURGERY Vol. 16 ( 2 ) page： 262 - 265 2023.4

Mizuno, M

NUTRIENTS Vol. 15 ( 8 ) 2023.4

特集 Genetics in CKD 疾患編補体関連遺伝子の異常と腎疾患

金恒秀, 水野正司

腎と透析 Vol. 94 ( 3 ) page： 405 - 410 2023.3

Durvalumab plus carboplatin-etoposide treatment in a patient with small-cell lung cancer on hemodialysis: A case report and literature review. Reviewed Open Access

Ushijima F, Hase T, Yamashita Y, Kim H, Shimokata T, Kondo C, Sato T, Baba T, Watanabe S, Futamura K, Ando Y, Mizuno M, Ishii M.

Int Cancer Conf J. Vol. 13 ( 2 ) page： 88 - 92 2023.2

Case report: Thrombotic microangiopathy concomitant with macrophage activation syndrome in systemic lupus erythematosus refractory to conventional treatment successfully treated with eculizumab Invited Reviewed International journal Open Access

Makoto Yamaguchi, Masashi Mizuno, Fumiya Kitamura, Shiho Iwagaitsu, Hironobu Nobata, Hiroshi Kinashi, Shogo Banno, Akimasa Asai, Takuji Ishimoto, Takayuki Katsuno, Yasuhiko Ito

Frontiers in Medicine Vol. 9 page： 1097528 2023.1

Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Macrophage activation syndrome (MAS) is also a rare, life-threatening hyperinflammatory condition that is comorbid with SLE. However, the association between TMA and MAS in patients with SLE has rarely been assessed, and the difficulty of diagnosing these conditions remains prevalent. The efficacy of eculizumab has been reported for SLE patients whose conditions are complicated with TMA. However, no study has investigated the therapeutic efficacy of eculizumab for TMA concomitant with SLE-associated MAS. Herein, we report the first case of TMA concomitant with SLE-associated MAS that was initially refractory to conventional immunosuppressive therapy but showed remarkable recovery after eculizumab treatment. Furthermore, we evaluated serum syndecan-1 and hyaluronan levels, which are biomarkers of endothelial damage. We found that these levels decreased after the administration of eculizumab, suggesting that TMA was the main pathology of the patient. This case illustrates that it is important to appropriately assess the possibility of TMA during the course of SLE-associated MAS and consider the use of eculizumab as necessary.

DOI： 10.3389/fmed.2022.1097528

Recurrent Cerebrovascular Complications under Enzyme Replacement Therapy in a Patient with Fabry Disease on Peritoneal Dialysis Reviewed International journal

Muto Reiko, Suzuki Yasuhiro, Shimizu Hideaki, Yasuda Kaoru, Ishimoto Takuji, Maruyama Shoichi, Ito Yasuhiko, Mizuno Masashi

Internal Medicine Vol. 62 ( 3 ) page： 565 - 569 2023

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

Fabry disease is an X-linked lysosomal storage disorder due to mutations in the alpha-galactosidase A gene, which leads to the accumulation of globotriaosylceramide in various organs. In Fabry disease with end-stage renal disease (ESRD), cerebrovascular events are lethal, even with enzyme replacement therapy (ERT). However, the utility of biomarkers to evaluate the ERT response is unclear. We herein report a case of recurrent cerebrovascular complications under ERT in a Fabry disease patient, progressing to ESRD on peritoneal dialysis. Further studies are warranted, but Fabry disease patients with ESRD receiving ERT might need careful long-term follow-up in cases with cerebrovascular manifestations.

DOI： 10.2169/internalmedicine.0185-22

ASSISTED PD：Problems and Countermeasures Based on Home-Visit Nursing Station Surveys Reviewed

Takai Nami, Nakabayashi Kichio, Kawashima Shoichi, Mizuno Masashi, Koide Shigehisa, Kasuga Hirotake, Saka Yosuke, Sakai Emiko, Inaguma Daijo, Ito Yasuhiko

Nihon Toseki Igakkai Zasshi Vol. 56 ( 11 ) page： 401 - 409 2023

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：The Japanese Society for Dialysis Therapy

[Objective] To investigate factors hindering the spread of assisted peritoneal dialysis (PD) to support elderly patients in Japan, a survey of PD acceptance at home nursing stations was administered. [Method] A questionnaire survey was conducted involving 616 home-visit nursing stations in Aichi Prefecture, 368 of which were registered with the Aichi Medical Association or Aichi Council of Home-Visit Nursing Stations. [Results] A total of 132 facilities were surveyed, for a collection rate of 35％. The breakdown was as follows：37 home nursing stations were accepting PD patients, 59 were considering accepting PD patients, and 20 were not considering accepting PD patients. A total of 20％ of the facilities were always involved in PD patient visits. Other facilities had only a few opportunities to see PD patients per year. The most common conditions for acceptance by visiting nurses were："medication management" and "emotional support," followed by "PD-bag exchange" and "exit site care". The most common considerations for acceptance were："preparation of APD cycler" and "monitoring the operation of APD equipment," such as preparation of APD equipment. [Conclusion] In order for home health care nurses, who are key personnel in ASSISTED PD, to be able to accept PD patients without anxiety, collaboration and multidisciplinary cooperation, such as joint visits and sharing of care methods with medical staff at PD treatment facilities, are required.

DOI： 10.4009/jsdt.56.401

CiNii Research

Long-term peritoneal dialysate exposure modulates expression of membrane complement regulators in human peritoneal mesothelial cells Reviewed International journal

Kobayashi Kazuma, Ozeki Toshikazu, Kim Hangsoo, Imai Masaki, Kojima Hiroshi, Iguchi Daiki, Fukui Sosuke, Suzuki Masafumi, Suzuki Yasuhiro, Maruyama Shoichi, Ito Yasuhiko, Mizuno Masashi

FRONTIERS IN MEDICINE Vol. 9 page： 972592 2022.12

Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice. Reviewed International journal

Hiroya Tanaka, Ting Sun, Hiroshi Kinashi, Keisuke Kamiya, Makoto Yamaguchi, Hironobu Nobata, Fumiko Sakata, Hangsoo Kim, Masashi Mizuno, Shunnosuke Kunoki, Yukinao Sakai, Akiyoshi Hirayama, Tomoyoshi Soga, Kazuhiro Yoshikawa, Takuji Ishimoto, Yasuhiko Ito

American journal of physiology. Renal physiology Vol. 323 ( 6 ) page： F654 - F665 2022.12

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

Cardiovascular disease is the most common comorbidity in chronic kidney disease (CKD) patients, affecting both their prognosis and quality of life. Cardiac fibrosis is common in CKD patients with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-a, IL-1b, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) as compared with Nx-salt mice treated with control rat immunoglobulin G1 (rat IgG1) (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites including histidine and γ-butyrobetaine were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, anti-fibrotic, and partial anti-oxidative effects in the heart of Nx-salt mice.

DOI： 10.1152/ajprenal.00396.2021

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