Yasuhiro Suzuki

Nagoya University, Nagoya, Aichi, Japan

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Publications (22)75.19 Total impact

  • Masashi Mizuno, Yasuhiro Suzuki, Yasuhiko Ito
    Internal Medicine 01/2014; 53(6):647. · 0.97 Impact Factor
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    ABSTRACT: In patients receiving peritoneal dialysis, fungal or yeast peritonitis has a poor prognosis. In rat peritoneum with mechanical scraping, severe peritonitis can be induced by zymosan, a component of yeast (Zy/scraping peritonitis). Administration of rat adipose tissue-derived stromal cells (ASCs) potentially can improve several tissue injuries. The present study investigated whether rat ASCs could improve peritoneal inflammation in Zy/scraping peritonitis. Rat ASCs were injected intraperitoneally on a daily basis in rats with Zy/scraping peritonitis. Peritoneal inflammation accompanied by accumulation of inflammatory cells and complement deposition was suppressed by day 5 after injection of rat ASCs. The peritoneal mesothelial layer in Zy/scraping peritonitis with rat ASC treatment was restored compared with the peritoneal mesothelial layer without rat ASC treatment. Injected rat ASCs co-existed with mesothelial cells in the sub-peritoneal layer. In vitro assays showed increased cellular proliferation of rat mesothelial cells combined with rat ASCs by co-culture assays, confirming that fluid factors from rat ASCs might play some role in facilitating the recovery of rat mesothelial cells. Hepatocyte growth factor was released from rat ASCs, and administration of recombinant hepatocyte growth factor increased rat mesothelial cell proliferation. Because the peritoneal mesothelium shows strong expression of membrane complement regulators such as Crry, CD55 and CD59, restoration of the mesothelial cell layer by rat ASCs might prevent deposition of complement activation products and ameliorate peritoneal injuries. This study suggests the therapeutic possibilities of intraperitoneal rat ASC injection to suppress peritoneal inflammation by restoring the mesothelial layer and decreasing complement activation in fungal or yeast peritonitis.
    Cytotherapy 12/2013; · 3.06 Impact Factor
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    ABSTRACT: ESRD treated with dialysis is associated with increased left ventricular hypertrophy, which, in turn, is related to high mortality. Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure; however, the effects in patients undergoing dialysis remain uncertain. We conducted a multicenter, open-label, prospective, randomized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without (control group) spironolactone for 2 years. As a primary endpoint, rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 (P=0.03), 18 (P=0.004), and 24 (P=0.01) months in patients taking spironolactone compared with the control group. Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment (P=0.02). The benefits of spironolactone were clear in patients with reduced residual renal function. As secondary endpoints, renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period. No serious adverse effects, such as hyperkalemia, occurred. In this trial, spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis, without significant adverse effects. Further studies, including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints, should confirm these data in a larger cohort.
    Journal of the American Society of Nephrology 12/2013; · 8.99 Impact Factor
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    ABSTRACT: Peritoneal fibrosis (PF) causes ultrafiltration failure (UFF) and is a complicating factor in long-term peritoneal dialysis. Lymphatic reabsorption also may contribute to UFF, but little is known about lymphangiogenesis in patients with UFF and peritonitis. We studied the role of the lymphangiogenesis mediator vascular endothelial growth factor-C (VEGF-C) in human dialysate effluents, peritoneal tissues, and peritoneal mesothelial cells (HPMCs). Dialysate VEGF-C concentration correlated positively with the dialysate-to-plasma ratio of creatinine (D/P Cr) and the dialysate TGF-β1 concentration. Peritoneal tissue from patients with UFF expressed higher levels of VEGF-C, lymphatic endothelial hyaluronan receptor-1 (LYVE-1), and podoplanin mRNA and contained more lymphatic vessels than tissue from patients without UFF. Furthermore, mesothelial cell and macrophage expression of VEGF-C increased in the peritoneal membranes of patients with UFF and peritonitis. In cultured mesothelial cells, TGF-β1 upregulated the expression of VEGF-C mRNA and protein, and this upregulation was suppressed by a TGF-β type I receptor (TGFβR-I) inhibitor. TGF-β1-induced upregulation of VEGF-C mRNA expression in cultured HPMCs correlated with the D/P Cr of the patient from whom the HPMCs were derived (P<0.001). Moreover, treatment with a TGFβR-I inhibitor suppressed the enhanced lymphangiogenesis and VEGF-C expression associated with fibrosis in a rat model of PF. These results suggest that lymphangiogenesis associates with fibrosis through the TGF-β-VEGF-C pathway.
    Journal of the American Society of Nephrology 08/2013; · 8.99 Impact Factor
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    ABSTRACT: In peritoneal dialysis (PD) therapy, physical stresses such as exposure to peritoneal dialysate, catheter trauma and peritonitis induce peritoneal injuries which can prevent continued long-term PD therapy. Therefore, protection of the peritoneum is an important target to enable long-term PD therapy in patients with end-stage renal disease. We previously showed that neutralizations of membrane complement regulators (CRegs), Crry and CD59, in rat peritoneum provokes development of acute peritoneal injuries due to uncontrolled complement activation. C5a is a key effecter molecule of the complement system, released during acute inflammation. Control of C5a has been proposed as a strategy to suppress inflammatory reactions and, because peritoneal injuries are accompanied by inflammation, we hypothesized that C5a targeted therapy might be an effective way to suppress peritoneal injuries. In the present study, we have used the established acute peritonitis model induced by neutralization of CRegs to investigate effects on acute peritoneal injuries of inhibiting C5a. Intravenous administration of an anti-C5a complementary peptide (AcPepA) up to 4 h after induction of injury significantly and dose-dependently prevented accumulation of inflammatory cells and reduced tissue damage in the model, accompanied by decreased C3b deposition. Here we showed that C5a contributed to the development of peritoneal injuries. Our results suggest that C5a is a target to prevent or treat peritoneal injuries in PD patients on prolonged therapy or with infectious complications.
    AJP Renal Physiology 07/2013; · 4.42 Impact Factor
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    ABSTRACT: A 46-year-old man on peritoneal dialysis (PD) was hospitalized due to suspicious PD-related peritonitis. Because the patient's abdominal pain was unimproved by conventional antibiotics and multiple bacteria were identified in a smear-sample of PD fluid, endogenous peritonitis was suspected. Perforated appendicitis was finally diagnosed under exploratory laparotomy. In this patient, perforated appendicitis was difficult to diagnose due to the attenuated clinical symptoms and inconclusive results of abdominal computed tomography (CT), even though the positive predictive value of CT is >95% in non-PD patients. Quickly deciding to perform exploratory laparotomy in patients suspected of having endogenous peritonitis is thus important, even when the origin has not been clarified.
    Internal Medicine 01/2013; 52(11):1177-1181. · 0.97 Impact Factor
  • Immunobiology 11/2012; 217(11):1144. · 2.81 Impact Factor
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    ABSTRACT: Non-steroidal anti-inflammatory drugs decrease the glomerular filtration rate. However, few studies have been conducted on renal function in patients treated with non-steroidal anti-inflammatory drugs during the first week after laparoscopic radical nephrectomy. The purpose of this study is to determine whether short-term administration of non-steroidal anti-inflammatory drugs during the first week after laparoscopic radical nephrectomy is a risk factor for impaired renal function. Renal carcinoma patients undergoing laparoscopic radical nephrectomy in Nagoya University Hospital from April 2004 to July 2010 were identified in a retrospective cohort study. The 164 patients were divided into non-non-steroidal anti-inflammatory drug-treated (n = 50) and non-steroidal anti-inflammatory drug-treated (n = 114) groups. Elderly patients (>60 years old) in the non-steroidal anti-inflammatory drug-treated group showed a significant correlation between the residual renal function ratio and the total dose of diclofenac sodium (r = -0.277, P < 0.05). There was no significant correlation between the residual renal function ratio and the total dose of loxoprofen sodium. The time to doubling of the serum creatinine level was significantly shorter in elderly patients treated with diclofenac sodium compared with that in patients treated with non-non-steroidal anti-inflammatory drugs (P = 0.034). These results suggest that renal ischemia induced by short-term administration of diclofenac sodium impairs renal function in elderly patients after laparoscopic radical nephrectomy. In the present study, we found the first evidence that short-term administration of diclofenac sodium is one risk factor for renal impairment after laparoscopic radical nephrectomy in elderly patients. To prevent renal impairment after laparoscopic radical nephrectomy in elderly patients, the use of loxoprofen sodium, which has a negligible effect on renal function compared with diclofenac sodium, is recommended.
    Japanese Journal of Clinical Oncology 09/2012; 42(11):1073-8. · 1.90 Impact Factor
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    ABSTRACT: Protein-energy wasting and chronic inflammation are prevalent in patients with end-stage renal disease (ESRD). We investigated the combination of serum albumin, C-reactive protein (CRP) and body mass index (BMI) at initiation of hemodialysis therapy as a predictor of all-cause and cardiovascular disease (CVD) mortality in Japanese ESRD patients. A total of 1,228 consecutive Japanese ESRD patients on hemodialysis therapy were enrolled and followed for up to 10 years. Patients were divided into quartiles according to levels of albumin, CRP and BMI. Furthermore, to clarify the joint role of these factors, albumin <3.5 g/dl, CRP >4.0 mg/l and BMI <19.6 were defined as risk factors using receiver operating characteristic analysis; thereafter, patients were divided into groups according to the positive number of these factors. Adjusted hazard ratios (HRs) for lower serum albumin, elevated CRP and lower BMI for 10-year all-cause mortality were 1.97, 3.13 and 2.61, respectively. Regarding the combination of these variables, adjusted HRs for mortality were 2.31, 4.28 and 8.07, respectively, in patients having any one factor, any two factors and all three factors. The C-index for an established risk model with these three positive markers was the most accurate for predicting mortality (0.768), as compared to other models with one or two markers. Similar results were seen for CVD mortality. Serum albumin, CRP and BMI at the start of hemodialysis therapy were able to individually stratify the risk of long-term mortality in ESRD patients. Furthermore, a combination of these variables could more accurately predict mortality.
    American Journal of Nephrology 07/2012; 36(2):136-43. · 2.62 Impact Factor
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    ABSTRACT: Oxaliplatin is effective in advanced colorectal cancer and is known to have relatively few side effects, such as hemolysis and renal toxicity. We report a case of acute kidney injury (AKI) after treatment with a combination of oxaliplatin, folinic acid and 5-fluorouracil or capecitabine. The patient developed acute renal failure, hemolytic anemia and thrombocytopenia after the 34th course of chemotherapy including oxaliplatin. A positive direct antiglobulin test and detection of immunoglobulin G and complement C3b and C3d on erythrocytes suggested the diagnosis of immune-related severe intravascular hemolytic anemia. She was successfully treated and recovered using plasma exchange, corticosteroids and hemodialysis therapy. Only seven other cases of AKI associated with oxaliplatin use have been reported to date. As in this case, acute hemolysis due to autoimmune mechanisms and subsequent AKI occurred suddenly after frequent use of oxaliplatin in four of those cases. We should be aware that oxaliplatin may cause sudden life-threatening hemolysis by drug-induced antibodies and subsequent AKI, even though oxaliplatin is frequently administered without side effects. This represents the first case report of AKI-related hemolysis due to oxaliplatin in Japan.
    Clinical and Experimental Nephrology 03/2012; 16(3):490-4. · 1.25 Impact Factor
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    ABSTRACT: 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.
    AJP Renal Physiology 02/2012; 302(10):F1245-51. · 4.42 Impact Factor
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    ABSTRACT: Inflammation is recognized as an important contributor to lymphangiogenesis; however, in tubulointerstitial lesions in human chronic kidney diseases, this process is better correlated with the presence of myofibroblasts rather than macrophages. As little is known about the interaction between lymphangiogenesis and renal fibrosis, we utilized the rat unilateral ureteral obstruction model to analyze inflammation, fibrosis, lymphangiogenesis, and growth factor expression. Additionally, we determined the relationship between vascular endothelial growth factor-C (VEGF-C), an inducer of lymphangiogenesis, and the profibrotic factor, transforming growth factor-β1 (TGF-β1). The expression of both TGF-β1 and VEGF-C was detected in tubular epithelial and mononuclear cells, and gradually increased, peaking 14 days after ureteral obstruction. The kinetics and localization of VEGF-C were similar to those of TGF-β1, and the expression of these growth factors and lymphangiogenesis were linked with the progression of fibrosis. VEGF-C expression was upregulated by TGF-β1 in cultured proximal tubular epithelial cells, collecting duct cells, and macrophages. Both in vitro and in vivo, the induction of VEGF-C along with the overall appearance of lymphatics in vivo was specifically suppressed by the TGF-β type I receptor inhibitor LY364947. Thus, TGF-β1 induces VEGF-C expression, which leads to lymphangiogenesis.
    Kidney International 01/2012; 81(9):865-79. · 7.92 Impact Factor
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    ABSTRACT: Colonic diverticulitis is an important cause of polymicrobial peritonitis, which requires surgical treatment and cessation of peritoneal dialysis (PD). The aim of this study was to examine whether plain abdominal computed tomography (CT) is useful for evaluating colonic diverticulosis in chronic kidney disease (CKD) patients and to explore whether colonic diverticulosis is a risk factor for enteric peritonitis. The subjects consisted of 137 consecutive CKD patients (Stage 4 or 5) who were candidates for PD from February 2005 to November 2009. Abdominal CT without contrast media was performed in all PD candidates. Diverticula of the colon were detected by plain CT in 57 cases (41.6%). The number of diverticula tended to increase with age. The most common site of involvement of diverticulosis was the ascending colon. In patients treated with PD, the incidence of peritonitis was higher in patients with diverticulosis than in those without diverticulosis (P = 0.004). However, only one episode of enteric peritonitis was observed among patients with diverticulosis. The presence of diverticulosis did not affect cumulative or technical survival. PD was not selected in four cases due to a high frequency of diverticula with episodes of abdominal pain. Two cases developed severe diverticulitis with peritonitis and underwent resection of the colon. Our study suggests that plain CT examination is useful for detecting diverticulosis in CKD patients. Silent diverticulosis is not a risk factor for enteric diverticulosis-related peritonitis. PD may be contraindicated in cases having frequent diverticulosis with episodes of lower abdominal pain.
    Nephrology Dialysis Transplantation 12/2011; 27(6):2511-6. · 3.37 Impact Factor
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    ABSTRACT: We report a case of peritonitis resulting from colon perforation caused by ingestion of a rare foreign body in a patient on peritoneal dialysis (PD). A 72-year-old woman on PD was hospitalized with abdominal pain and cloudy PD fluid (PDF). Although conventional antibiotic therapy was started because of a diagnosis of infectious peritonitis, low-grade fever, abdominal pain and a high number of white blood cells in PDF persisted. On day 3, anaerobic bacteria were recognized on bacterial culture of PDF, suggesting a gastrointestinal etiology. During exploratory laparotomy, sigmoidal perforation by a piece of bamboo, probably resulting from ingestion of contaminated food, was found.
    Clinical and Experimental Nephrology 09/2011; 15(6):962-5. · 1.25 Impact Factor
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    ABSTRACT: 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. 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. 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 drop-out 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. 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.
    Clinical and Experimental Nephrology 06/2011; 15(5):727-37. · 1.25 Impact Factor
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    ABSTRACT: Atrial natriuretic peptide (ANP) was recently reported to ameliorate fibrosis in the heart and experimental renal diseases and vascular thickening after balloon injury. Peritoneal fibrosis is an important complication of long-term peritoneal dialysis, and peritonitis is a factor in its onset. In the present study, we investigated the effects of ANP in a rat peritonitis-induced peritoneal fibrosis model. As pretreatment, an osmotic pump containing vehicle (saline) or ANP (0.15 or 0.3 μg/min) was inserted through the carotid vein in male Sprague-Dawley rats. ANP or saline was continuously infused using the osmotic pump. Three days after administration of ANP or saline, rats underwent peritoneal scraping in a blind manner and were sacrificed on Day 14. The effects of ANP were evaluated based on peritoneal thickness, immunohistochemistry and real-time polymerase chain reaction. In each experiment, we evaluated messenger RNA (mRNA) expression of the ANP receptor natriuretic peptide receptor A (NPR-A) in the peritoneum after scraping. The effects of ANP were also studied in cultured peritoneal fibroblasts and mesothelial cells. We observed a significant increase in NPR-A mRNA in the peritoneum. Peritoneal thickness increased with time and peaked on Day 14, but ANP significantly reduced peritoneal thickness. Parameters such as number of macrophages and CD-31-positive vessels and expression of type III collagen/transforming growth factor-β/plasminogen activator inhibitor-1 (PAI-1)/connective tissue growth factor (CTGF) were significantly suppressed by ANP. In cultured peritoneal fibroblasts and mesothelial cells, ANP suppressed angiotensin II-induced upregulation of CTGF and PAI-1. Our results suggest that ANP is useful in preventing inflammation-induced peritoneal fibrosis.
    Nephrology Dialysis Transplantation 06/2011; 27(2):526-36. · 3.37 Impact Factor
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    ABSTRACT: A 54-year-old woman on peritoneal dialysis (PD) was hospitalized with peritonitis with a high body temperature, abdominal pain and cloudy peritoneal fluid. She progressively fell into septic-like shock within only 6 hours after onset. The causative bacteria were Streptococcus mitis (S. mitis), part of the normal flora of oral cavity, intestine, female genial tract and upper respiratory tract. S. mitis shows pathogenicity for diseases such as endocarditis, brain abscesses and sepsis in children with malignancy or transplantation. However, S. mitis rarely shows severe pathogenic responses in adults. We report herein a case of fulminant peritonitis caused by S. mitis in an adult PD patient.
    Internal Medicine 01/2011; 50(5):471-4. · 0.97 Impact Factor
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    ABSTRACT: A 68-year-old man was admitted with acute renal failure caused by cholesterol embolization after undergoing carotid artery stenting. Hemodialysis therapy (HD) was immediately required because of uremia, using nafamostat mesilate as an anticoagulant for HD. However, blue toes and gangrene of the feet worsened. To prevent use of anticoagulants and stabilize BP, HD was changed to peritoneal dialysis (PD). After starting PD, blue toes and gangrene improved markedly. Residual renal function also partially recovered. Although BP was unstable during HD, stability of BP and avoidance of anticoagulants during PD therapy might have contributed to the good results.
    Internal Medicine 01/2011; 50(16):1719-23. · 0.97 Impact Factor
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    ABSTRACT: High baseline peritoneal solute transport rate is reportedly associated with reduced patient and technique survival in continuous peritoneal dialysis (PD) patients. However, the determinants of baseline peritoneal solute transport rate remain uncertain. The aim of this study was to investigate the relationship between peritoneal local inflammation, angiogenesis and systemic inflammation and baseline peritoneal permeability. Peritoneal biopsy specimens from 42 pre-dialysis uraemic patients and 11 control individuals were investigated. Immunohistochemistry for CD68-positive macrophages, chymase- and tryptase-positive mast cells, interleukin-6 (IL-6)-positive cells, CD3-positive T cells, CD20-positive B cells, neutrophils and CD31- and pathologische anatomie Leiden-endothelium (PAL-E)-positive blood vessels in the peritoneum was performed. Baseline dialysate-to-plasma ratio for creatinine (D/P Cr) was determined within 6 months of PD induction. Clinical and laboratory parameters were measured at the time of peritoneal biopsy. Factors associated with peritoneal permeability were assessed by multiple linear regression analysis. Pre-dialysis uraemic peritoneum showed infiltration by CD68-positive macrophages, and mast cells, as compared with controls. Baseline D/P Cr was correlated with density of CD68-positive macrophages (P < 0.001), IL-6-positive cells (P < 0.001), CD31-positive (P < 0.05) and PAL-E-positive blood vessels (P < 0.05) and serum albumin (P < 0.05). However, baseline peritoneal permeability was not correlated with infiltration by mast cells, B cells, T cells, neutrophils, serum C-reactive protein or other clinical factors. On multiple linear regression analysis, the number of CD68-positive macrophages in peritoneum was an independent predictor for baseline peritoneal permeability (P = 0.009). Peritoneal macrophage infiltration is predominant in uraemic patients and is an important factor in predicting baseline peritoneal permeability.
    Nephrology Dialysis Transplantation 11/2010; 26(7):2322-32. · 3.37 Impact Factor
  • Molecular Immunology - MOL IMMUNOL. 01/2010; 47(13):2270-2270.

Publication Stats

76 Citations
75.19 Total Impact Points


  • 2011
    • Nagoya University
      Nagoya, Aichi, Japan
    • Meijo University
      • Faculty of Pharmacy
      Nagoya-shi, Aichi-ken, Japan