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The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD).

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested.

OBJECTIVE--We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS--Subjects were 198 type [...]

Background: The use of exchange devices for peritoneal dialysis (PD) fluids is a common practice in Japan. Evidence on the effectiveness of exchange devices in preventing PD-related peritonitis is scarce. We evaluated the association between the use of exchange devices for PD fluids and peritonitis incidence.Methods: We retrospectively enrolled 3845 patients, aged ≥20 years, receiving PD for ≥3 months, with available data on the exchange procedure for PD fluids and peritonitis incidence that was obtained from the Japan Renal Data Registry, a nationwide annual survey. The patients were grouped according to whether the manual or device PD fluid exchange method was used. The onset of peritonitis was defined as a leukocyte count of >100/µL (neutrophils ≥50%) in PD effluents. We applied quasi-Poisson regression analyses to estimate the incidence rate ratio (IRR). Age, sex, PD vintage, body mass index, automated PD use, residual kidney function, comorbidities, haemoglobin and serum albumin were adjusted as potential confounders.Results: Older age, automated PD use, diabetes as comorbidity and lower haemoglobin levels were associated with the use of exchange devices for PD fluids. Patients using devices for PD fluid exchange (69.2%) had an increased risk of peritonitis of 37% (IRR: 1.37, 95% confidence interval (CI): 1.07–1.75) and 28% (IRR: 1.28, 95% CI: 1.00–1.63) in the crude and multivariate adjustment models, respectively.Conclusions: The use of exchange devices for PD fluids and peritonitis incidence showed no favourable association. There may remain possible residual confounding by indication.

Methotrexate (MTX)-associated B-cell lymphoproliferative disorders (B-LPD) may first present in the skin. Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is now a well known disease listed in the 2017 World Health Organization classification. However, primary cutaneous MTX-associated B-LPD (pcMTX B-LPD), other than EBVMCU, appear to be underestimated, and their distinctiveness remains unproven. This study aimed to document the clinicopathological characteristics of nine patients with pcMTX B-LPD that were not EBVMCU to extend our understanding of this peculiar disease.

The clinical utility of a recently developed bioabsorbable polyglycolic acid (PGA) spacer has not yet been established in pediatric patients; therefore, we aimed to investigate its utility during chemo-proton therapy for pediatric cancer. Proton depth–dose curves were obtained in a water phantom with or without the spacer. Computed tomography (CT) scans were performed for the PGA spacer immersed in saline for 2 weeks to measure CT numbers and estimate the relative stopping power (RSP) for the proton beams. The spacer was placed in a patient with sacral Ewing sarcoma receiving 55.8 Gy [relative biological effectiveness (RBE)] in 31 fractions and was evaluated using CT scans performed every other week. In addition, the images were used to quantitatively evaluate changes in volume and RSP of the spacer and dose distributions in normal tissues. The spacer immersed in saline had a CT number of 91 ± 7 (mean ± standard deviation) Hounsfield units, and the corresponding RSP was predicted to be 1.07 ± 0.01. The measured RSP agreed with the predicted one. The volumes of the large bowel and rectum receiving ≥45 Gy(RBE) (V45Gy) were significantly reduced by placing the spacer; V45Gywithout and with the spacer were 48.5 and 0.01%, respectively, for the rectum and 7.2 and 0%, respectively, for the large bowel. The volume of the spacer and RSP decreased at rates of 4.6 and 0.44% per week, respectively, whereas the target dose coverage was maintained until the end of treatment. The PGA spacer was considered effective for pediatric cancer patients undergoing chemo-proton therapy.

Background: Although percutaneous transluminal angioplasty has been established as a first-line therapy for access failure in dialysis, there are few reports on primary patency after percutaneous transluminal angioplasty. We investigated factors associated with primary patency following the first percutaneous transluminal angioplasty performed after vascular access construction in patients with arteriovenous fistula, including blood flow volume before and after percutaneous transluminal angioplasty and previously reported factors.Methods: We used medical records at six dialysis centers to retrospectively identify and analyze prognostic factors for primary patency after percutaneous transluminal angioplasty in 159 patients with arteriovenous fistula who underwent initial percutaneous transluminal angioplasty after vascular access construction.Results: Multivariate analysis with the Cox proportional hazard model showed that primary patency after percutaneous transluminal angioplasty in patients with arteriovenous fistula was significantly associated with lesion length (hazard ratio, 1.76; 95% confidence interval, 1.01–3.07; P = 0.045), and blood flow volume after percutaneous transluminal angioplasty (hazard ratio, 0.71; 95% confidence interval, 0.60–0.84; P < 0.001). When blood flow volume after percutaneous transluminal angioplasty was classified into three categories, risks of outcome events defining the end of primary patency after percutaneous transluminal angioplasty were significantly lower for 400–630 mL/min (hazard ratio, 0.38; 95% confidence interval, 0.21–0.68; P = 0.001) and >630 mL/min (hazard ratio, 0.16; 95% confidence interval, 0.06–0.40; P < 0.001) compared with <400 mL/min.Conclusion: Our study showed that blood flow volume after percutaneous transluminal angioplasty is an important prognostic factor for primary patency after percutaneous transluminal angioplasty in patients with arteriovenous fistula.

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Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology–Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Introduction: We report a case in which we performed an anastomotic part septal formation surgery (anastoplasty) and artificial blood vessel replacement surgery.Case Description: When forearm arteriovenous fistula occlusion of a dialysis patient was observed, there was a thrombus in the vein of the whole forearm from the anastomotic part. We performed a septum formation surgery to suppress the blood flow in the vein near the anastomotic site, and artificial blood vessel replacement was performed on the high stenosis of the cephalic vein of the elbow. Postoperative blood flow was stable and hemodialysis was possible. Although there are various blood flow suppression methods for suppressing excessive blood flow, we report a case in which an anastomotic part septal formation surgery and artificial blood vessel replacement to secure an outflow passage were performed at the same time.Conclusion: Anastoplasty for excessive blood flow is considered to be an effective means in this case.

Background: Clinical data supporting the target haemoglobin range in patients undergoing peritoneal dialysis (PD) are scarce. This study investigated the association between haemoglobin levels and all-cause mortality in Japanese patients undergoing PD using data from a nationwide dialysis registry.Methods: A total of 4875 patients aged ≥18 years who were undergoing PD at the end of 2012 were analysed. Patients receiving combination therapy with haemodialysis or missing haemoglobin data were excluded. Haemoglobin values were categorised into six groups (<9.0, 9.0–9.9, 10.0–10.9, 11.0–11.9, 12.0–12.9 and ≥13.0 g/dL) and their association with mortality evaluated.Results: Patients’ mean age was 63 years, and 62% were men. The mean haemoglobin level was 10.7 g/dL, and 14% were anuric. Erythropoiesis-stimulating agents were used in 89%. During a median follow-up of 3.5 years, 1586 patients died. Haemoglobin levels <9.0 and ≥13.0 g/dL were significantly associated with mortality, as compared with levels of 10.0–10.9 g/dL (adjusted hazard ratios [95% confidence intervals]: 1.25 [1.06–1.48] and 1.45 [1.13–1.88], respectively). Restricted cubic spline analysis revealed a U-shaped association between haemoglobin levels and mortality. A haemoglobin level ≥12 g/dL was associated with mortality in patients with a history of cardiovascular disease (pinteraction = 0.023).Conclusion: We provide important insights into the target haemoglobin in patients undergoing PD. Our findings suggest that setting a lower upper limit for haemoglobin levels may be beneficial for patients with a history of cardiovascular disease.

In a previous study of fungal peritoneal injury in peritoneal dialysis patients, complement (C)-dependent pathological changes were developed in zymosan (Zy)-induced peritonitis by peritoneal scraping. However, the injuries were limited to the parietal peritoneum and did not show any fibrous encapsulation of the visceral peritoneum, which differs from human encapsular peritoneal sclerosis (EPS). We investigated peritoneal injury in a rat model of Zy-induced peritonitis pretreated with methylglyoxal (MGO) instead of scraping (Zy/MGO peritonitis) to clarify the role of C in the process of fibrous encapsulation of the visceral peritoneum. Therapeutic effects of an anti-C5a complementary peptide, AcPepA, on peritonitis were also studied. In Zy/MGO peritonitis, peritoneal thickness, fibrin exudation, accumulation of inflammatory cells, and deposition of C3b and C5b-9 with loss of membrane C regulators were increased along the peritoneum until day 5. On day 14, fibrous encapsulation of the visceral peritoneum was observed, resembling human EPS. Peritoneal injuries and fibrous changes were significantly improved with AcPepA treatment, even when AcPepA was administered following injection of Zy in Zy/MGO peritonitis. The data show that C5a might play a role in the development of encapsulation-like changes in the visceral peritoneum in Zy/MGO peritonitis. AcPepA might have therapeutic effects in fungal infection-induced peritoneal injury by preventing subsequent development of peritoneal encapsulation.

The characteristic features of chronic peritoneal injury with peritoneal dialysis (PD) are submesothelial fibrosis and neoangiogenesis. Transforming growth factor (TGF)β and vascular endothelial growth factor (VEGF)-A are the main mediators of fibrosis and neoangiogenesis, respectively; however, the effect of the interaction between them on the peritoneum is not well known. In this study, we investigated the relationship between TGF-β1 and VEGF-A in inducing peritoneal fibrosis by use of human tissues and dialysate, cultured cells, and animal models. The VEGF-A concentration correlated with the dialysate-to-plasma ratio of creatinine (D/P Cr) (P< 0.001) and TGF-β1 (P< 0.001) in human PD effluent. VEGF-A mRNA levels increased significantly in the peritoneal tissues of human ultrafiltration failure (UFF) patients and correlated with number of vessels (P< 0.01) and peritoneal thickness (P< 0.001). TGF-β1 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-β1-induced VEGF-A was suppressed by TGF-β receptor I (TGFβR-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-β1 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D/P Cr (P< 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGFβR-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGFβR-I inhibitor administration in the CG model decreased peritoneal thickness (P< 0.001), the number of vessels (P< 0.001), and VEGF-A levels (P< 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its possible involvement in lymphangiogenesis has not been explored. We found prominent lymphangiogenesis during tubulointerstitial fibrosis to be associated with increased expression of CTGF and VEGF-C in human obstructed nephropathy as well as in diabetic kidney disease. Using CTGF knockout mice, we investigated the involvement of CTGF in development of fibrosis and associated lymphangiogenesis in obstructive nephropathy. The increase of lymphatic vessels and VEGF-C in obstructed kidneys was significantly reduced in CTGF knockout compared to wild-type mice. Also in mouse kidneys subjected to ischemia-reperfusion injury, CTGF knockdown was associated with reduced lymphangiogenesis. In vitro, CTGF induced VEGF-C production in HK-2 cells, while CTGF siRNA suppressed transforming growth factor β1–induced VEGF-C upregulation. Furthermore, surface plasmon resonance analysis showed that CTGF and VEGF-C directly interact. Interestingly, VEGF-C–induced capillary-like tube formation by human lymphatic endothelial cells was suppressed by full-length CTGF but not by naturally occurring proteolytic CTGF fragments. Thus, CTGF is significantly involved in fibrosis-associated renal lymphangiogenesis through regulation of, and direct interaction with, VEGF-C.

Protein energy wasting (PEW) is consistently associated with poor prognosis in hemodialysis (HD) patients. We compared the predictability of PEW as diagnosed by The International Society of Renal Nutrition and Metabolism criteria (PEWISRNM) and geriatric nutritional risk index (GNRI) for all-cause mortality in Japanese HD patients. As cut-off values for body mass index (BMI) for PEW have not been established in PEWISRNMfor Asian populations, these were also investigated.

Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells. Macrophage infiltration in the peritoneal wall (P<0.001), heart (P<0.05) and para-aortic tissues (P<0.001) was significantly higher in 5/6Nx with salt loading (5/6Nx/NaCl) than in 5/6Nx without salt loading (5/6Nx/Water); however, there were no significant differences in blood pressure and renal function between the groups. Tissue interleukin-6, monocyte chemotactic protein-1 (MCP-1), serum- and glucocorticoid-inducible kinase 1 (Sgk1) and tonicity-responsive enhancer binding protein (TonEBP) mRNA were significantly elevated in the peritoneal wall and heart with 5/6Nx/NaCl when compared with 5/6Nx/Water. Sodium was stored in the abdominal wall, exerting high-osmotic conditions. Reversal of salt loading reduced macrophage infiltration associated with decreased TonEBP in 5/6Nx/NaCl. Macrophage infiltration associated with fibrosis induced by salt loading was decreased in the 5/6Nx/NaCl/CC chemokine receptor 2 (CCR2, receptor of MCP-1)-deficient mice when compared with 5/6Nx/NaCl/Wild mice, suggesting that CCR2 is required for macrophage infiltration in 5/6Nx with NaCl loading. In cultured mesothelial cells and cardiomyocytes, culture media with high NaCl concentration induced MCP-1, Sgk1 and TonEBP mRNA, all of which were suppressed by TonEBP siRNA, indicating that both MCP-1 and Sgk1 are downstream of TonEBP. Our study indicates that high NaCl intake induces MCP-1 expression leading to macrophage infiltration via the TonEBP-MCP-1 pathway in 5/6Nx/NaCl mice, and that TonEBP has a central role in inflammation in patients with renal failure taking high salt.

Long-term peritoneal dialysis (PD) is often associated with peritoneal dysfunction leading to withdrawal from PD. The characteristic pathologic features of peritoneal dysfunction are widely attributed to peritoneal fibrosis and angiogenesis. The detailed mechanisms remain unclear, and treatment targets in clinical settings have yet to be identified. We investigated transglutaminase 2 (TG2) as a possible novel therapeutic target for peritoneal injury. TG2 and fibrosis, inflammation, and angiogenesis were investigated in a chlorhexidine gluconate (CG)-induced model of peritoneal inflammation and fibrosis, representing a noninfectious model of PD-related peritonitis. Transforming growth factor (TGF)-β type I receptor (TGFβR-I) inhibitor and TG2-knockout mice were used for TGF-β and TG2 inhibition studies, respectively. Double immunostaining was performed to identify cells expressing TG2 and endothelial-mesenchymal transition (EndMT). In the rat CG model of peritoneal fibrosis, in situ TG2 activity and protein expression increased during the development of peritoneal fibrosis, as well as increases in peritoneal thickness and numbers of blood vessels and macrophages. TGFβR-I inhibitor suppressed TG2 activity and protein expression, as well as peritoneal fibrosis and angiogenesis. TGF-β1 expression, peritoneal fibrosis, and angiogenesis were suppressed in TG2-knockout mice. TG2 activity was detected by α-smooth muscle actin-positive myofibroblasts, CD31-positive endothelial cells, and ED-1-positive macrophages. CD31-positive endothelial cells in the CG model were α-smooth muscle actin-positive, vimentin-positive, and vascular endothelial-cadherin-negative, suggesting EndMT. In the CG model, EndMT was suppressed in TG2-knockout mice. TG2 was involved in the interactive regulation of TGF-β. As inhibition of TG2 reduced peritoneal fibrosis, angiogenesis, and inflammation associated with TGF-β and vascular endothelial growth factor-A suppression, TG2 may provide a new therapeutic target for ameliorating peritoneal injuries in PD.

Various novel molten salt electrochemical processes can be used to create new industries in the fields of energy, the environment, resources, and materials. Of these, the following four topics are selected, and their principles, experimental data, and current developmental stages towards industrialization are explained. (1) Electrolytic synthesis of ammonia from water and nitrogen under atmospheric pressure; (2) Electrochemical formation of carbon film; (3) Plasma-induced discharge electrolysis to produce nano-particles; and (4) Recycling of crucial metals using a 'bifunctional' electrode.

The CD98 heavy chain (CD98hc) regulates virus-induced cell fusion and monocyte fusion, and is involved in amino acid transportation. Here, we examined the role that CD98hc plays in the formation of osteoclasts using CD98hcflox/floxLysM-cre peritoneal macrophages (CD98hc-defect macrophages). Peritoneal macrophages were stimulated with co-cultured with osteoblasts in the presence of 1,25(OH)2vitamin D3, and thereafter stained with tartrate-resistant acid phosphatase staining solution. The multinucleated osteoclast formation was severely impaired in the peritoneal macrophages isolated from the CD98hc-defect mice compared with those from wild-type mice. CD98hc mediates integrin signaling and amino acid transport through the CD98 light chain (CD98lc). In integrin signaling, suppression of the M-CSF-RANKL-induced phosphorylation of ERK, Akt, JNK and p130Cas were observed at the triggering phase in the CD98h-defect peritoneal macrophages. Moreover, we showed that the general control non-derepressible (GCN) pathway, which was activated by amino acid starvation, was induced by the CD98hc-defect peritoneal macrophages stimulated with RANKL. These results indicate that CD98 plays two important roles in osteoclast formation through integrin signaling and amino acid transport.

As a rare complication in patients on peritoneal dialysis (PD), increase of eosinophil (peritoneal dialysate fluid [PDF] eosinophilia), including eosinophilic peritonitis, was observed in PDF. The majority of eosinophilic peritonitis cases are detected during the early phase of PD induction. However, the frequency of and mechanisms underlying PDF eosinophilia remain unclear. We therefore investigated the frequency of PDF eosinophilia and what mechanisms, specifically complement activation, might contribute to its occurrence. In 48 patients, eosinophil counts and concentrations of complement activation products, such as C3a, C5a, and sC5b-9, interleukin (IL)-5, and IL-6 in PDF were evaluated on days 1, 2, and 4 after starting PD therapy. We focused on the relationships between patient background characteristics and eosinophil counts and levels of C3a, C5a, and sC5b-9 as complement activation products in PDF. In 33.3% of PD patients, increased PDF eosinophils were observed on day 1. Eosinophil counts correlated with PDF levels of C3a on days 1 and 2, IL-5 on days 1, 2, and 4, and IL-6 on day 1. In terms of background characteristics, only the duration the PD catheter was left in place differed significantly between PDF eosinophilia and non-PDF eosinophilia. Notably, PDF levels of C3a differed significantly between patients with and without eosinophilia, suggesting that C3a might be a candidate for induction of increased eosinophil.PDF eosinophilia was frequently observed during PD initiation. Our results suggest that PD catheter insertion and complement activation might be related to increases in eosinophils in PDF during PD initiation.

BackgroundTolvaptan selectively binds to the vasopressin V2 receptor and inhibits reabsorption of free water. Although its effi cacy for heart failure has been proven, its effi cacy for chronic kidney disease (CKD) patients has not been assessed in detail.MethodsWe examined 20 CKD patients (13 men and 7 women) who presented with volume overload and who were administered tolvaptan. We assessed urine volume (UV) and blood biochemistry before administration (d0), 1 day after administration (d1), and 7 to 14 days after administration (d7-14).ResultsThe mean age was 74.0) 13.1 years. Besides CKD, there were 9, 8, and 5 patients with heart failure, liver failure or liver cirrhosis, and severe oedema, respectively. UV signifi cantly increased from 959.0 ) 503.8 mL/day at d0 to 1605.4 ) 964.0 mL/day at d7-14 (P <0.01). Serum creatinine levels were not exacerbated (3.89) 3.43 mg/dL at d0 and 3.66) 3.02 mg/dL at d7-14). Serum albumin (ALB) levels and urinary protein creatinine ratio (uPCR) did not correlate with UV change. Estimated glomerular fi ltration rate (eGFR) correlated with UV change from d0 to d1 (r = 0.6619, P< 0.01). Serum sodiume levation correlated with increased UV (r = 0.4951, P< 0.05).ConclusionTolvaptan is useful to reduce volume overload without exacerbation of the renal function; its eff ect does not depend on ALB or uPCR. The eGFR correlated with the effi cacy of tolvaptan. If UV increases drastically after tolvaptan administration, serum Na levels should be carefully monitored.

Infection and inflammation suppress the expression and activity of several drug transporters in liver. In the intestine, P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) are important barriers to the absorption of many clinically important drugs. The expression and activity of these proteins were examined under inflammation. Drug transport was determined in jejunum and ileum segments isolated from 1.0 mg/kg, 5.0 mg/kg, and 7.5 mg/kg indomethacin-treated or control rats in diffusion chambers. Transport of laminaran, used as a model compound of (1-3) β-D-glucan, was measured for 120 min in the presence or absence of inhibitors. Reverse transcription-polymerase chain reaction was used to measure mRNA levels. Compared with controls, levels of Mdr1a mRNA were significantly decreased in the jejunum and ileum of 7.5 mg/kg indomethacin-treated rats. Both reductions in the basolateral to apical efflux of laminaran and increases in the apical to basolateral influx of laminaran were observed, resulting in significant increases in the apical to basolateral absorption of laminaran in 7.5 mg/kg indomethacin-treated rats. The inhibitory effect of verapamil on laminaran transport was observed in control rats but not in indomethacin-treated rats. Fluorescein isothiocyanate dextran 40,000 permeability, membrane resistance, and claudin-4 mRNA level were not altered, indicating no change in the paracellular pathway. These results indicate that indomethacin-induced inflammation reduces the intestinal expression and activity of P-gp in rats, which elicits corresponding changes in the intestinal transport of laminaran. Hence, inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters.

Objective.The diagnostic values of antiproteinase 3 and antimyeloperoxidase tests using antineutrophil cytoplasmic antibodies (ANCA) are well established. Our study determined whether an increase in ANCA level was a predictor of disease flareup.Methods.Our study included 126 patients with ANCA-associated renal vasculitis treated at 9 nephrology centers in Japan. The relationship between increased ANCA levels and relapse was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors. The outcome of interest was the time from remission to first relapse.Results.During the observation period [median 41 mos, interquartile range (IQR) 23–66 mos], 118 patients (95.8%) achieved remission at least once. After achieving remission, 34 patients relapsed (21.7%). Time-dependent multivariate Cox regression models revealed that lung involvement (adjusted HR 2.29, 95% CI 1.13–4.65, p = 0.022) and increased ANCA levels (adjusted HR 17.4, 95% CI 8.42–36.0, p < 0.001) were significantly associated with relapse. The median time from ANCA level increase to relapse was 0.6 months (IQR 0–2.1 mos).Conclusion.In our study, an increase in ANCA level during remission was associated with a risk of disease relapse. A rise in ANCA level may be useful for guiding treatment decisions in appropriate subsets of patients with ANCA-associated vasculitis.

In peritoneal dialysis (PD) therapy, physical stresses such as exposure to peritoneal dialysate, catheter trauma, and peritonitis may induce peritoneal injury that 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 neutralization of the membrane complement regulators (CRegs) Crry and CD59 in rat peritoneum provokes development of acute peritoneal injury 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 injury is accompanied by inflammation, we hypothesized that C5a targeted therapy might be an effective way to suppress peritoneal injury. In the present study we used an established acute peritonitis model induced by neutralization of CRegs to investigate the effects on acute peritoneal injury 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. We show that C5a contributed to the development of peritoneal injury. Our results suggest that C5a is a target for preventing or treating peritoneal injury in patients undergoing prolonged PD therapy or with infectious complications.

Current studies suggest that mesenchymal stromal cells (MSCs) improve acute kidney injury (AKI) via paracrine/ endocrine effects. We established human adipose tissue-derived stromal cells (hASCs) cultured in low (2%) serum (hLASCs), which have great potential of tissue regeneration. The present study was performed to investigate the therapeutic effects of hLASCs on AKI and to clarify the mechanisms involved. In low serum, hASCs proliferated well, while human bone marrow-derived stromal cells (hBMSCs) did not. hLASCs secreted higher levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) than did hASCs cultured in high (20%) serum (hHASCs) or hBMSCs cultured in high serum (hHBMSCs). AKI was induced in nude rats by folic acid, and hLASCs, hHASCs or control medium were administered into the renal subcapsules. hLASCs significantly attenuated acute renal damage, while hHASCs showed far less effect. Furthermore, interstitial fibrosis observed on day 14 was less pronounced in the hLASCs group. Cell tracking experiment showed no evidence of transdifferentiation. Intravenous injection of hLASCs or hHBMSCs or subcapsular injection of hHBMSCs did not ameliorate AKI. Concerning the mechanisms, our in vivo experiments showed that HGF knockdown by siRNA impaired the ability of hLASCs to protect the kidney from acute injury whereas VEGF knockdown did not. In conclusion, hLASCs, but not hHASCs or hHBMSCs, ameliorated AKI via paracrine effects, and HGF is one of the key mediators.

Cardiac valve calcification is seen frequently in patients undergoing dialysis. Serum C-reactive protein (CRP) level also is reported to predict future cardiovascular events. We investigated the association among valve calcification, CRP level, and mortality in patients with end-stage renal disease who were just beginning hemodialysis (HD) therapy.

Little is known about the CD98 heavy chain (CD98hc) in the T lymphocyte–mediated immune response to alloantigen.

Various electrochemical processes using molten salt can contribute to the realization of new energy systems directed toward low carbon society. Among these the following two promising processes are selected and described in detail: (1) Electrolytic synthesis of ammonia directly from water and nitrogen, and (2) Electrochemical formation of carbon film. In addition, the expected roles of molten salt electrochemical process in a nuclear field are described.

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 Immunol183: 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.

The dissolution behavior of ammonia (NH3) in a molten LiCl-KCl-CsCl system was studied in order to determine the feasibility of low-energy NH3 production via electrochemical synthesis in a high temperature molten salt system. In the presence of nitride ion (N3[?]), a portion of NH3 chemically dissolved in the melt as imide (NH2[?]) and amide (NH2[?]) anions formed by the reaction between N3[?] and NH3. Although the dissolved NH2[?] anion thermally decomposed to form NH3 and NH2[?] anion, this phenomena may lower the yield of electrochemical NH3 production. The dissolved NH3 can be recovered by supplying hydrogen or water vapor to the melt. The anodic reaction between N3[?] and H2 to form NH3 at a hydrogen gas-diffusion electrode was also examined and the NH3 yield was estimated. Although the competing N2 evolution reaction occurred at potentials more positive than 1.2 V vs. Li(I)/Li, the conversion of Li3N approached 70%, following the recovery processes.

Transforming growth factor (TGF)-β1, -β2, and -β3are involved in control of wound repair and development of fibrosis. Connective tissue growth factor (CTGF) expression is stimulated by all TGF-β isoforms and is abundant in glomerulosclerosis and other fibrotic disorders. CTGF is hypothesized to mediate profibrotic effects of TGF-β1or to facilitate interaction of TGF-β1with its receptor, but its interactions with TGF-β isoforms in nonpathological conditions are unexplored so far. Tissue repair and remodeling may recapitulate gene transcription at play in organogenesis. To further delineate the relationship between CTGF and TGF-β, we compared expression patterns of CTGF and TGF-β isoforms in rat and human glomerulogenesis and in various human glomerulopathies. CTGF mRNA was present in the immediate precursors of glomerular visceral and parietal epithelial cells in the comma- and S-shaped stages, but not in earlier stages of nephron development. During the capillary loop and maturing glomerular stages and simultaneous with the presence of TGF-β1, -β2, and -β3protein, CTGF mRNA expression was maximal and present only in differentiating glomerular epithelial cells. CTGF protein was also present on precursors of mesangium and glomerular endothelium, suggesting possible paracrine interaction. Concomitant with the presence of TGF-β2and -β3protein, and in the absence of TGF-β1, CTGF mRNA and protein expression was restricted to podocytes in normal adult glomeruli. However, TGF-β1and CTGF were again coexpressed, often with TGF-β2and -β3, in particular in podocytes in proliferative glomerulonephritis and also in mesangial cells in diabetic nephropathy and IgA nephropathy (IgA NP). Coordinated expression of TGF-β isoforms and of CTGF may be involved in normal glomerulogenesis and possibly in maintenance of glomerular structure and function at adult age. Prolonged overexpression of TGF-β1and CTGF is associated with development of severe glomerulonephritis and glomerulosclerosis.

Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n= 178) and tissue CTGF expression (n= 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-β1stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n= 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-β1-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF-β1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.

Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis therapy. The present study was performed to examine the mechanisms of PF in view of the plasminogen activator (PA)/plasmin/matrix metalloproteinase (MMP) cascade. PF was induced in tissue-type PA (tPA) deficient mice and wild-type mice by intraperitoneal injection of chlorhexidine gluconate. Mice were killed on day 21, and tissue samples were taken. Histopathological studies were performed. Plasmin activity, gelatinases activity, and the levels of tPA, transforming growth factor-β1 (TGF-β1), and MMP-2 mRNA were determined. Protein levels of MMP-3, tissue inhibitor of metalloproteinases (TIMP)-1, -2, and -3, phospho-Smad3, membrane-type 1 (MT1)-MMP, and MT3-MMP were also studied. On day 21, tPA +/+ mice showed severe PF, whereas tPA −/− mice showed milder change. Submesothelial basement membranes were dissolved in tPA +/+ mice while they were relatively preserved in tPA −/− mice. The levels of macrophage infiltration, staining for α-smooth muscle actin (α-SMA) and collagen type III, and vascular density were all significantly lower in tPA −/− mice than in tPA +/+ mice. The levels of plasmin activity, pro- and active MMP-2, mRNA expression of tPA and TGF-β1, and phospho-Smad3 protein were also lower in tPA −/− mice. No difference was observed between the two groups concerning the protein levels of MMP-3, TIMP-1, TIMP-2, TIMP-3, MT1-MMP, or MT3-MMP. These results indicate that the presence of tPA enhances inflammation, angiogenesis, and fibrogenesis in the peritoneum of the PF model mice. Activation of the PA/plasmin/MMP cascade may play a pivotal role in the pathogenesis of PF.

Road meteorological observatories measure visibility with visibility meters. However, visibility values measured by visibility meters stem from the meteorological definition, which comes from a perspective different from that of road use. Subject experiments were therefore conducted with road videos in blowing snow conditions to clarify the difference between visibility perceived by drivers and that measured with a visibility meter. The experiments revealed that visibility perceived by drivers in blowing snow was approximately 70 m lower than conventionally measured visibility. Also, a high correlation was observed between the visibility perceived by drivers and the sum total of projected area of snow particles passed through a unit area in a unit time. It was also learned that the visibility perceived by drivers during blowing snow was affected by the intensity of visibility fluctuation, the presence or absence of snowfall, road surface conditions, the surrounding environment (i.e., urban or suburban), and the time of day, and is hardly influenced at all by the direction of the snowstorm. On the basis of the above results, the need for a visibility index for road traffic in blowing snow was suggested.

Peritoneal fibrosis (PF) is an important complication of long-term peritoneal dialysis. Although mineralocorticoid and mineralocorticoid receptor (MR) have attracted increasing attention in the field of vascular injury, including the heart, kidney, and vessels, little is known about the role of mineralocorticoid in PF. This work was designed to explore the effects of MR blockade on PF. We developed a new model of PF in rats based on mechanical scraping of the peritoneum. This model is characterized by acute-phase inflammation (neutrophil and macrophage infiltration on days 0–3) and late-phase PF (α-smooth muscle actin-positive fibroblast infiltration, type III collagen accumulation, and neoangiogenesis on days 7–14). Peritoneal thickening peaked on day 14. MR was expressed in rat peritoneum and a rat fibroblast cell line. Expression of its effector kinase [serum- and glucocorticoid-induced kinase-1 (Sgk1)], transforming growth factor-β (TGF-β), plasminogen activator inhibitor-1 (PAI-1), and CD31-positive vessels increased during the course of PF. Rats were treated with spironolactone, angiotensin receptor blockade (ARB), or angiotensin-converting enzyme inhibitor (ACEI)-ARB-spironolactone starting at 6 h after peritoneal scraping. All parameters, including peritoneal thickening, number of macrophages and CD31-positive vessels, and expression of monocyte chemoattractant protein-1, TGF-β, PAI-1, and Sgk1, were significantly suppressed by spironolactone (10 mg·kg−1·day−1). The effects of spironolactone (10 and 20 mg·kg−1·day−1) were very similar to those of triple blockade. ARB, but not ACEI, significantly reduced peritoneal thickening. Furthermore, peritoneal function assessed by peritoneal equilibration test was significantly improved by spironolactone. Our results suggest that MR is a potential target to prevent inflammation-induced PF in patients on peritoneal dialysis.

AbstractBackground/Aim:The high mobility group box chromosomal protein 1 (HMGB1), a nuclear DNA-binding protein, has recently been recognized as a new proinflammatory cytokine. The purpose of this study was to examine the significance of HMGB1 in patients with renal diseases. Methods:HMGB1 concentrations in sera were measured by enzyme-linked immunosorbent assay, and antibodies against HMGB1 were examined by Western blotting in patients who underwent renal biopsies and in healthy controls. Immunohistochemistry for HMGB1 was also performed. Results:Serum HMGB1 was more likely to be positive in patients who underwent renal biopsies as compared with the controls. Patients with anti-neutrophil cytoplasmic antibody-related glomerulonephritis (ANCA-GN) and those with Henoch-Schönlein purpura nephritis showed a significantly higher tendency to be HMGB1 positive. The presence of anti-HMGB1 antibody was not associated with the presence of serum HMGB1. Immunohistochemistry revealed that HMGB1 was expressed in mononuclear cells in the interstitium or in the glomeruli of some patients with ANCA-GN or IgA nephropathy (IgAN). Subanalysis demonstrated that among patients with IgAN, those who had crescent formation showed a higher tendency to be HMGB1 positive than those who did not. Conclusions:HMGB1 was expressed in the sera of patients with renal diseases who underwent renal biopsies, especially among those who had vasculitis including ANCA-GN, Henoch-Schönlein purpura nephritis, and IgAN with glomerular crescents.Copyright © 2008 S. Karger AG, Basel

When K562 cells were infected with Newcastle disease virus (NDV) or human parainfluenza type 2 virus (hPIV‐2), polykaryocyte formation could not be detected. Failure of multinucleated giant cell formation in K562 cells infected with either NDV or hPIV‐2 is due to disturbance of the viral envelope‐cell fusion step or to defect in the cell‐cell fusion step, respectively. Especially, NDV completely replicated in K562 cells, and the hemagglutinin‐neuraminidase and fusion proteins expressed on the cell surface of NDV‐infected K562 cell were fully functional for fusion inducing activity. Therefore, the cell membranes of K562 cells are considered to be resistant to virus‐induced cell fusion. Membrane fusion is regulated by many host factors including membrane fluidity, cytoskeletal systems, and fusion regulatory proteins system. An unknown regulatory mechanism of virus‐induced cell fusion may function on the cell surface of K562 cells.

Electrochemical behavior of an isotropic graphite electrode in a LiBr-KBr-CsBr eutectic melt was investigated at 523 K to apply to the anode for high power density lithium-ion batteries. It was confirmed that the electrochemical lithium intercalation/deintercalation into/from the graphite occurred reversibly, accompanied with the stepwise stage formation of lithium-graphite compounds. The capacity for lithium intercalation was at and coulombic cycle efficiency was max 98%. (c) 2003 The Electrochemical Society. All rights reserved.