Faculty Profiles - MIZUNO, Masashi

Eculizumab for pediatric dense deposit disease: A case report and literature review. Reviewed International journal

Katsuaki Kasahara, Yoshimitsu Gotoh, Hisakazu Majima, Asami Takeda, Masashi Mizuno

Clinical nephrology. Case studies Vol. 8 page： 96 - 102 2020

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Dense deposit disease (DDD), a subtype of complement component 3 (C3) glomerulopathy (C3G), results from alternative complement pathway hyperactivity leading to membrane attack complex formation. DDD treatment strategies are limited. We report a case of a 13-year-old girl diagnosed with DDD at 9 years of age, with nephritic and nephrotic syndrome and C3 nephritic factor-negative alternative complement pathway activation. Initial treatment with prednisolone, methylprednisolone pulses (MPs), and mizoribines was effective for 3 years, after which she relapsed. Despite MP treatment followed by prednisolone and mycophenolate mofetil (MMF), her kidney function and proteinuria deteriorated with a high soluble (s)C5b-9 level; she also developed dyspnea and pleural effusion (PE). Three days after the first eculizumab (ECZ) infusion, urine volume increased, respiratory condition improved, PE resolved, and proteinuria decreased in 1 month. Serum creatinine level decreased, and kidney function completely normalized within 7 weeks. The sC5b-9 level normalized, and although proteinuria decreased, nephrotic range proteinuria persisted during ECZ treatment with MMF for 53 weeks, even with increased treatment interval. Thus, complement activation pathway-targeted therapy may be useful for rapidly progressing DDD. Our data support the role of complement pathway abnormalities in C3G with DDD.

DOI： 10.5414/CNCS110309

Safety and effectiveness of eculizumab for adult patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Reviewed International journal

Hideki Kato, Yoshitaka Miyakawa, Yoshihiko Hidaka, Norimitsu Inoue, Shuichi Ito, Shoji Kagami, Shinya Kaname, Masanori Matsumoto, Masashi Mizuno, Takahisa Matsuda, Akihiko Shimono, Shoichi Maruyama, Yoshihiro Fujimura, Masaomi Nangaku, Hirokazu Okada

Clinical and experimental nephrology Vol. 23 ( 1 ) page： 65 - 75 2019.1

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

BACKGROUND: Eculizumab has been available for the treatment of atypical hemolytic-uremic syndrome (aHUS) in Japan since 2013. To assess safety and effectiveness of eculizumab in adult aHUS patients in the real-life setting, we performed interim analysis of a post-marketing surveillance mandated by Japanese regulations. METHODS: This study enrolled any patient who was diagnosed with TMA excluding Shiga toxin-producing Escherichia coli-HUS or thrombotic thrombocytopenic purpura based on Japanese clinical guide published in 2013 as inclusion criteria and treated with eculizumab. Although the term aHUS was redefined to denote only complement-mediated HUS in the guide revised in 2016, the patients with TMA caused by other causes (secondary TMA) were included. Patient outcomes and safety were evaluated at 6 months, 12 months, and annually thereafter. RESULTS: Thirty-three patients with aHUS and 27 patients with secondary TMA were enrolled. Median treatment duration of aHUS was 24weeks. Complement genes variants were detected in 11 of 18 patients with aHUS (61.1%). Among the 29 aHUS patients with available baseline data, platelet count (PLT), lactic dehydrogenase and serum creatinine (SCr) improved within 1-month after eculizumab initiation. TMA event-free status, complete TMA response, PLT normalization, and SCr decrease were achieved in 67.9% (19/28), 27.8% (5/18), 56.5% (13/23), and 57.1% (16/28) of patients, respectively. Thirty-three and 11 adverse reactions were observed in patients with aHUS (13/33 patients) and secondary TMA (6/27 patients), respectively. CONCLUSIONS: This interim analysis confirmed the acceptable safety profile and effectiveness of eculizumab for Japanese adult aHUS patients in real-world settings.

DOI： 10.1007/s10157-018-1609-8

Safety and effectiveness of eculizumab for pediatric patients with atypical hemolytic-uremic syndrome in Japan: interim analysis of post-marketing surveillance. Reviewed International journal

Shuichi Ito, Yoshihiko Hidaka, Norimitsu Inoue, Shinya Kaname, Hideki Kato, Masanori Matsumoto, Yoshitaka Miyakawa, Masashi Mizuno, Hirokazu Okada, Akihiko Shimono, Takahisa Matsuda, Shoichi Maruyama, Yoshihiro Fujimura, Masaomi Nangaku, Shoji Kagami

Clinical and experimental nephrology Vol. 23 ( 1 ) page： 112 - 121 2019.1

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

BACKGROUND: In 2013, eculizumab was approved for treatment of the atypical hemolytic-uremic syndrome (aHUS) in Japan, which was defined as a thrombotic microangiopathy (TMA) excluding Shiga toxin-producing Escherichia coli-HUS and thrombotic thrombocytopenic purpura. Simultaneously, post-marketing surveillance was started to assess its safety and effectiveness. In 2016, Japanese clinical guide redefined terms to limit the use of "aHUS" to complement-mediated HUS only. Accordingly, TMA with other causes was defined as secondary TMA. Here we report the interim analysis of post-marketing surveillance of pediatric patients with aHUS and secondary TMA. METHODS: Pediatric patients treated with eculizumab from approval to 15 March 2017 were included in this observational real-world study. Clinical endpoints of effectiveness were TMA event-free status, complete TMA response, platelet count normalization, and improvement of estimated glomerular filtration rate (eGFR). Adverse reactions to eculizumab were also analyzed. RESULTS: In 27 pediatric patients with aHUS, median age at diagnosis was 4 years. Complement genes' variants were detected in 14 of 21 patients (66.7%). Median time from diagnosis to eculizumab initiation was 2.0 days. TMA event-free status, complete TMA response, platelet normalization, and improvement in eGFR were achieved in 85.2, 36.4, 78.3, and 75.0% of patients, respectively. Three patients with aHUS died. Twenty-four and 10 adverse reactions were reported in 31 aHUS patients and 17 secondary TMA patients, respectively; however, no eculizumab-related death or meningococcal infection was reported. CONCLUSIONS: This interim analysis confirmed that eculizumab is well-tolerated and effective for Japanese pediatric patients with aHUS in a real-world setting.

DOI： 10.1007/s10157-018-1610-2

Increase of Eosinophil in Dialysate During Induction of Peritoneal Dialysis. Reviewed International journal

Shigemoto E, Mizuno M, Suzuki Y, Kobayashi K, Sakata F, Kariya T, Katsuno T, Maruyama S, Ito Y

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis Vol. 39 ( 1 ) page： 90 - + 2019.1

Complement regulation and kidney diseases: recent knowledge of the double-edged roles of complement activation in nephrology Invited Reviewed International journal

Masashi Mizuno, Yasuhiro Suzuki, Yasuhiko Ito

Clinical and Experimental Nephrology Vol. 22 ( 1 ) page： 3 - 14 2018.2

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

The complement activation system plays important roles to maintain homeostasis in the host and to fight foreign invaders to protect the host. Therefore, the complement system is considered a core part of innate immunity which also cross-talks to acquired immunity. In the history of nephrology, the complement system is familiar to us, because complement protein or fragment deposition, including C3, C4, C1q, and/or C4d, is routinely estimated by immunohistochemistry to diagnose renal pathologies. The relationships between pathological mechanisms and complement activation have been investigated for renal diseases such as post-infectious glomerulonephritis, lupus nephritis, and primary membranoproliferative glomerulonephritis, which are usually accompanied by hypocomplementemia. However, unregulated complement activation in local areas might be associated with progression of various renal injuries even in the normocomplementemic patient. Recently, attention has focused on dysfunction of complement regulation in various diseases including renal diseases such as atypical hemolytic uremic syndrome and C3 glomerulopathy. Some mechanisms associated with complement activation in these diseases were clarified. In addition, lots of anti-complement agents were developed and some of the agents have become clinically available. Now, anti-complement therapies represent a realistic choice of therapeutic approaches for complement-related diseases. Research on roles of complement activation is proceeding into new stages in the field of nephrology and in other fields involving both basic and clinical research. We herein summarize relationships between the complement activation and regulation systems, their physiological effects and roles in maintenance of homeostasis in the host, and how dysregulation of the complement system triggers disease, especially renal disease.

DOI： 10.1007/s10157-017-1405-x

Mesangial proliferative glomerulonephritis in murine malaria parasite, Plasmodium chabaudi AS, infected NC mice Reviewed International journal

Akihito Yashima, Masashi Mizuno, Yukio Yuzawa, Koki Shimada, Norihiko Suzuki, Hideo Tawada, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Yasuhiko Ito, Seiichi Matsuo, Tamio Ohno

CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 21 ( 4 ) page： 589 - 596 2017.8

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Background Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites.
Methods NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed.
Results NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed mesangial proliferative glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection.
Conclusion The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.

DOI： 10.1007/s10157-016-1339-8

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients Reviewed International coauthorship International journal

Masashi Mizuno, Yasuhiro Suzuki, Keiko Higashide, Yumi Sei, Daiki Iguchi, Fumiko Sakata, Masanobu Horie, Shoichi Maruyama, Seiichi Matsuo, B. Paul Morgan, Yasuhiko Ito

PLOS ONE Vol. 12 ( 1 ) page： e0169111 2017.1

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

Background
We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis.
Methods
We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF.
Results
When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b- 9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms.
Conclusion
Our results suggested that levels of complement markers in PDF, especially sC5b- 9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

DOI： 10.1371/journal.pone.0169111

Recent analysis of status and outcomes of peritoneal dialysis in the Tokai area of Japan: the second report of the Tokai peritoneal dialysis registry Reviewed International journal

Masashi Mizuno, Yasuhiko Ito, Yasuhiro Suzuki, Fumiko Sakata, Yosuke Saka, Takeyuki Hiramatsu, Hirofumi Tamai, Makoto Mizutani, Tomohiko Naruse, Norimi Ohashi, Hirotake Kasuga, Hideaki Shimizu, Hisashi Kurata, Kei Kurata, Satoshi Suzuki, Satoko Kido, Yoshikazu Tsuruta, Teppei Matsuoka, Masanobu Horie, Shoichi Maruyama, Seiichi Matsuo

CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 20 ( 6 ) page： 960 - 971 2016.12

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

Early withdrawal within 3 years after starting peritoneal dialysis (PD) and PD-related peritonitis have been major obstacles preventing increases in the population of PD patients. To address these problems, we implemented education programs for medical staff. This study analyzed the recent status and outcomes of PD therapy, focusing on findings such as the incidence and prognosis of peritonitis as of 5 years after our last study.
We investigated background, laboratory data and status of PD therapy, reasons for withdrawal from PD and incidental statements on peritonitis from 2010 to 2012 (R2), and compared findings with those from our last study of 2005-2007 (R1).
Early PD therapy withdrawal in R2 clearly improved to 44.7 %, compared with 50.9 % in R1. Peritonitis incidence improved slightly from once per 42.8 months/patient in R1 to once per 47.3 months/patient in R2. Notably, PD-related peritonitis as a cause of mortality improved markedly in R2, but outcomes of PD-related peritonitis did not change significantly between R1 and R2. In contrast, social problems increased as a reason for withdrawal from PD therapy.
Our efforts at education might have been useful for improving early withdrawal from PD and deaths attributable to PD-related peritonitis. However, since improvements to incidence of PD-related peritonitis were limited by education, further improvement in PD-related peritonitis incidence requires development of new sterilized connecting systems during PD-bag exchanges to decrease PD-related peritonitis opportunities. Construction of medical support systems to address social problems is required to maintain long-term PD therapy.

DOI： 10.1007/s10157-016-1249-9

Expression of membrane complement regulators, CD46, CD55 and CD59, in mesothelial cells of patients on peritoneal dialysis therapy Reviewed International coauthorship International journal

Yumi Sei, Masashi Mizuno, Yasuhiro Suzuki, Masaki Imai, Keiko Higashide, Claire L. Harris, Fumiko Sakata, Daiki Iguchi, Michitaka Fujiwara, Yasuhiro Kodera, Shoichi Maruyama, Seiichi Matsuo, Yasuhiko Ito

MOLECULAR IMMUNOLOGY Vol. 65 ( 2 ) page： 302 - 309 2015.6

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

We investigated the expression of membrane complement regulators (CRegs), CD46, CD55 and CD59 in human mesothelial cells, and correlated with clinical background and level of complement (C) activation products in peritoneal dialysis (PD) fluids (PDF) to clarify influence of the C activation system in PD patients. Expression of CRegs was assessed on primary cultures of mesothelial cells (HPMC) harvested from PD fluid of 31 PD patients. Because expression of CD55 but not CD46 and CD59 in mesothelial cells was significantly correlated to value of dialysate-to-plasma creatinine concentration ratio (D/P Cre) (p<0.005) as an indicator of peritoneal function, we focused on analysis of CD55 expression of HPMCs in comparison with levels of C activation products in the PDF of the PD patients, and their background factors. When comparing expression of the CRegs between systemic neutrophils and HPMC, no correlation was observed, supporting that change of CRegs' expression in HPMC was independently occurring in the peritoneum. Expression of CD55 protein in HPMC was closely correlated with expression at the mRNA level (p<0.0001) and was inversely correlated with levels of sC5b-9 (p<0.05), but not C3, C4, IL6 and CA125 in the PDF. Complications of diabetes, usage of icodextrin and residual renal function were not correlated with change of CD55 expression in HPMCs.
Our data show that the process of PD therapy modifies expression of CD55 on peritoneal mesothelium and triggers local C activation. These findings support efforts to modify PD therapy to limit effects on activation and regulation of the C system. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.molimm.2015.02.005

Long-Term Effects of Spironolactone in Peritoneal Dialysis Patients Reviewed International journal

Ito Yasuhiko, Mizuno Masashi, Suzuki Yasuhiro, Tamai Hirofumi, Hiramatsu Takeyuki, Ohashi Hiroshige, Ito Isao, Kasuga Hirotake, Horie Masanobu, Maruyama Shoichi, Yuzawa Yukio, Matsubara Tatsuaki, Matsuo Seiichi

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 25 ( 5 ) page： 1094 - 1102 2014.5

Anti-C5a complementary peptide ameliorates acute peritoneal injuries induced by neutralization of Crry and CD59. Reviewed

Mizuno T, Mizuno M, Imai M, Suzuki Y, Kushida M, Noda Y, Maruyama S, Okada H, Okada N, Matsuo S, Ito Y.

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Vol. 305 ( 11 ) page： F1603 - F1616 2013

Exploiting the Nephrotoxic Effects of Venom from the Sea Anemone, Phyllodiscus semoni, to Create a Hemolytic Uremic Syndrome Model in the Rat Invited Reviewed International coauthorship International journal

Masashi Mizuno, Yasuhiko Ito, B. Paul Morgan

MARINE DRUGS Vol. 10 ( 7 ) page： 1582 - 1604 2012.7

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

In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection from predators, most sea anemones are harmless to man. However, a few species are highly toxic; some have venoms containing neurotoxins, recently suggested as potential immune-modulators for therapeutic application in immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has multiple effects, including lethality, hemolysis and renal injuries. We previously reported that venom extracted from Phyllodiscus semoni induced acute glomerular endothelial injuries in rats resembling hemolytic uremic syndrome (HUS), accompanied with complement dysregulation in glomeruli and suggested that the model might be useful for analyses of pathology and development of therapeutic approaches in HUS. In this mini-review, we describe in detail the venom-induced acute renal injuries in rat and summarize how the venom of Phyllodiscus semoni could have potential as a tool for analyses of complement activation and therapeutic interventions in HUS.

DOI： 10.3390/md10071582

Membrane complement regulators protect against fibrin exudation increases in a severe peritoneal inflammation model in rats Reviewed International coauthorship International journal

Masashi Mizuno, Yasuhiko Ito, Tomohiro Mizuno, Claire L. Harris, Yasuhiro Suzuki, Noriko Okada, Seiichi Matsuo, B. Paul Morgan

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Vol. 302 ( 10 ) page： F1245 - F1251 2012.5

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

Mizuno M, Ito Y, Mizuno T, Harris CL, Suzuki Y, Okada N, Matsuo S, Morgan BP. Membrane complement regulators protect against fibrin exudation increases in a severe peritoneal inflammation model in rats. Am J Physiol Renal Physiol 302: F1245-F1251, 2012. First published February 15, 2012; doi:10.1152/ajprenal.00652.2011.-Peritonitis and the rare sequela of encapsulating peritoneal sclerosis (EPS) are serious problems in patients on peritoneal dialysis therapy. Chronic and persistent peritoneal injuries may be a risk factor of EPS. We previously reported that a chronic, proliferative peritonitis developed when zymosan was administered intraperitoneally following scraping injury of rat peritoneum (Mizuno M, Ito Y, Hepburn N, Mizuno T, Noda Y, Yuzawa Y, Harris CL, Morgan BP, Matsuo S. J Immunol 183: 1403-1412, 2009). Peritoneal membrane complement regulators (CRegs), especially Crry and CD59, protected from injury by inhibiting local complement activation, suggesting that CRegs play important roles in maintaining homeostasis in rat peritoneum. Here, we investigated roles of complement in the development of EPS by neutralizing CReg function with monoclonal antibodies (MAbs). Proliferative peritonitis was induced by scraping the peritoneum, followed by daily intraperitoneal administration of zymosan. When either Crry or CD59 alone was neutralized by MAb, the tissue injuries were not significantly changed compared with rats without neutralizing MAb. When both Crry and CD59 were neutralized in this model, severe fibrin exudation was observed on the peritoneal surface on day 5, accompanied by inflammatory cell infiltration, resembling the early stages of development of EPS. Dense peritoneal deposition of C3 fragments and membrane attack complex were observed, along with the fibrin exudates. Intravenous administration of cobra venom factor, which profoundly activates complement, further enhanced these pathological changes. Our results show that complement activation in injured peritoneum drives peritoneal inflammation, and that enhancement of complement activation by inhibiting CReg and/or enhancing systemic activation contributes to the initiation of EPS; therefore, anti-complement agents might be of therapeutic value in humans for the treatment of EPS.

DOI： 10.1152/ajprenal.00652.2011

Peritonitis is still an important factor for withdrawal from peritoneal dialysis therapy in the Tokai area of Japan Reviewed International journal

Masashi Mizuno, Yasuhiko Ito, Akio Tanaka, Yasuhiro Suzuki, Hideki Hiramatsu, Midoriko Watanabe, Yoshikazu Tsuruta, Teppei Matsuoka, Isao Ito, Hiroshi Tamai, Hirotake Kasuga, Hideaki Shimizu, Hisashi Kurata, Daijo Inaguma, Takeyuki Hiramatsu, Masanobu Horie, Tomohiko Naruse, Shoichi Maruyama, Enyu Imai, Yukio Yuzawa, Seiichi Matsuo

CLINICAL AND EXPERIMENTAL NEPHROLOGY Vol. 15 ( 5 ) page： 727 - 737 2011.10

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

Background In Japan, the population of patients on peritoneal dialysis (PD) is <4% of the total number of patients with end-stage renal disease. Few systemic analyses have examined why the number of PD patients has not increased in Japan. We organized a registry to analyze PD patients and retrospectively investigated 561 PD patients (about 5% of all Japanese PD patients) from 13 hospitals in the Tokai area for 3 years from 2005.
Methods We investigated background, physical status, laboratory data, status of PD therapy, and the occurrence of PD-related complications, and analyzed reasons for withdrawal from PD.
Results Nutrition did not change significantly during our observation. Urinary volume showed continued decreases after the introduction period. In contrast, PD fluid demand and ultrafiltration volume were significantly increased. For calcium metabolism, multiple phosphate binders were required after the second year of PD therapy. Early dropout within 3 years after starting PD therapy comprised 50.9% of total withdrawals, with PD-related peritonitis as the most common reason, mainly caused by Gram-positive organisms. Incidence of peritonitis was 42.8 months/patient. Culture-negative results were obtained for 32% of peritonitis cultures. Diabetes affects the prognosis of PD therapy, but not the incidence of peritonitis.
Conclusion We examined clinical status over 3 years in the Tokai area. The results suggest that the incidence of peritonitis needs to be decreased to prevent early withdrawal of PD patients. Education systems to decrease the incidence of peritonitis and techniques to decrease culture-negative results might be important for improving the prognosis of peritonitis.

DOI： 10.1007/s10157-011-0471-8