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Abstract

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β₂-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigated the effects of human sera on β2m amyloid fibril formation. Although sera markedly inhibited amyloid fibril formation, the inhibitory effects were weaker for sera collected from dialysis patients than for control sera. When sera collected before and after maintenance dialysis treatments were compared, the latter inhibited amyloid fibril formation more than the former. These results indicate that, although the inhibitory effects of sera were deteriorated in long-term dialysis patients, they were ameliorated by maintenance dialysis treatments in the short term. Maintenance dialysis decreases the body weight by 5% and consequently increases the concentrations of serum components. Among these components, we found that serum albumin prevented amyloid fibril formation based on macromolecular crowding effects, and that the decreased serum albumin concentration in dialysis patients is a tertiary risk factor for the onset of DRA. The model was constructed assuming accumulative effects of three risk factors and may be useful for predicting the onset of DRA. Furthermore, the model suggested the importance of monitoring temporary and accumulated risks to prevent the development of amyloidoses in general, which occurs based on supersaturation-limited amyloid fibril formation in a crowded milieu.

DOI： 10.1101/2022.02.01.478730

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INTRODUCTION: Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have a high risk of falls, whereas the impairment in balance function and their types in HD compared with non-dialysis dependent (ND) CKD have not been fully evaluated. METHODS: We conducted a cross-sectional study to assess the balance function in 91 ND-CKD and 65 HD patients. The participants underwent the timed up-and-go test (TUG) to assess dynamic balance and length of the center of pressure (CoP) with open eyes or closed eyes to evaluate static balance. RESULTS: TUG, length of CoP with open eyes, and length of CoP with closed eyes were longer in HD patients compared with those with ND-CKD. Multiple regression analysis showed that dialysis treatment independently affected TUG and length of CoP with open eyes. CONCLUSION: The dynamic and static balance functions are impaired in HD patients compared with that ND-CKD patients. This article is protected by copyright. All rights reserved.

DOI： 10.1111/1744-9987.13931

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AIM: The nutritional risk index for Japanese hemodialysis (NRI-JH) is a nutritional screening tool for predicting mortality in patients undergoing hemodialysis; however, its utility in patients undergoing hemodialysis during long-term hospitalization who have a high risk of protein-energy wasting, is unclear. METHODS: This retrospective study assessed hospitalized patients undergoing hemodialysis during long-term care at a single hospital. The NRI-JH was calculated using body mass index, serum albumin level, total cholesterol level, and serum creatinine level. The patients were categorized into three risk groups-low, medium, and high. Dietary energy and protein intake were evaluated by dietitians. The association of NRI-JH risk with nutritional intake and mortality were examined. RESULTS: In total, 133 patients were analyzed. The NRI-JH risk was low in 24%, medium in 26%, and high in 50% of the patients. The patients in the high-risk group were older and had lower energy and protein intakes than those in the low- and medium-risk groups. High-risk patients showed shorter survival times than low- and medium-risk patients, and a high NRI-JH risk was associated with a high mortality rate (hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.08-4.77; p < 0.05). The association weakened when protein intake and C-reactive protein level were added as covariates (HR, 2.01; 95% CI, 0.95-4.28, p = 0.07). CONCLUSIONS: High NRI-JH risk was associated with low dietary nutritional intake and poor survival in patients undergoing hemodialysis during long-term hospitalization. Nutritional status evaluation and nutritional interventions may improve prognosis in this population.

DOI： 10.1007/s10157-022-02259-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Falls are a social problem that increase healthcare costs. Hemodialysis (HD) patients need to avoid falling because fractures increase their risk of death. Nutritional problems such as frailty, sarcopenia, undernutrition, protein-energy wasting (PEW), and cachexia may increase the risk of falls and fractures in patients with HD. This review aimed to summarize the impact of frailty, sarcopenia, undernutrition, PEW, and cachexia on falls in HD patients. The reported global incidence of falls in HD patients is 0.85–1.60 falls per patient per year. HD patients fall frequently, but few reports have investigated the relationship between nutrition-related problems and falls. Several studies reported that frailty and undernutrition increase the risk of falls in HD patients. Nutritional therapy may help to prevent falls in HD patients. HD patients’ falls are caused by nutritional problems such as iatrogenic and non-iatrogenic factors. Falls increase a person’s fear of falling, reducing physical activity, which then causes muscle weakness and further decreased physical activity; this cycle can cause multiple falls. Further research is necessary to clarify the relationships between falls and sarcopenia, cachexia, and PEW. Routine clinical assessments of nutrition-related problems are crucial to prevent falls in HD patients.

DOI： 10.3390/nu14153225

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BACKGROUND: Patients with chronic kidney disease undergoing hemodialysis (HD) have a high incidence of falls. Impairment of balance function is a risk factor for falls in the general elderly, and no report examining the association between balance dysfunction and fall incidence in HD patients exists. METHODS: This prospective cohort study was conducted at a single center. The timed-up-and-go test (TUG) as a dynamic balance function was performed and length of the center of pressure (CoP) as a static balance function was measured before and after the HD session at baseline. Data of the number and detailed information of accidental falls for 1 year were collected. Multiple regression analyses were performed to assess the relationships between the number of falls and balance function. RESULTS: Forty-three patients undergoing HD were enrolled in the study. During 1 year of observation, 24 (55.8%) patients experienced accidental falls. TUG time was longer, and CoP was shorter in the post-HD session than in the pre-HD session. Adjusted multiple regression analyses showed that the number of accidental falls was independently associated with TUG time in the pre-HD session (B 0.267, p < 0.001, R2 0.413) and that in the post-HD session (B 0.257, p < 0.001, R2 0.530), but not with CoP. CONCLUSIONS: Dynamic balance was associated with fall incidence in maintenance HD patients. The evaluation and intervention of dynamic balance function might reduce the risk of falls in HD patients. TRIAL REGISTRATION: This study was carried out with the approval of the Niigata Rinko Hospital Ethics Committee (approval number 2005-92) (Registered on December 11, 2019) and registered in The University Hospital Medical Information Network (registration number 000040618 ).

DOI： 10.1186/s12882-022-02877-6

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OBJECTIVES: Patients undergoing hemodialysis (HD) may have poor nutritional status and hyperphosphatemia. Nephrologists sometimes manage hyperphosphatemia by prescribing phosphate binders and/or recommending restriction of dietary phosphate including protein-rich foods; the later may, however, adversely affect nutritional status. DESIGN AND METHODS: The analysis includes 8805 HD patients on dialysis ≥ 120 days in 12 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 4 (2009-2011), from 248 facilities. The primary exposure variable was response to the following question: "For patients with serum albumin 3.0 g/dL and phosphate 6.0 mg/dL, do you recommend to (A) increase or (B) decrease/no change in dietary protein intake (DPI)?". The association between medical director's practice of recommending an increase in DPI and all-cause mortality was analyzed with Cox regression adjusted for potential confounders. Linear and logistic regressions were used to model the cross-sectional associations between DPI advice practice and intermediate markers of patient nutrition. RESULTS: Median follow-up was 1.6 years. In the case scenario, 91% of medical directors in North America had a practice of recommending DPI increase compared to 58% in Europe (range = 36%-83% across 7 countries) and 56% in Japan. The practice of advising DPI increase was weakly associated with lower mortality [HR (95% CI): 0.88 (0.76-1.02)]. The association tended to be stronger in patients with age 70+ years [HR (95% CI): 0.82 (0.69-0.97), P = .12 for interaction]. The practice of advising DPI increase was associated with 0.276 mg/dL higher serum creatinine levels (95% CI: 0.033-0.520) after adjustment for case mix. CONCLUSIONS: Medical director's practice of recommending an increase in DPI for HD patients with low albumin and high phosphate levels was associated with higher serum creatinine levels and potentially lower all-cause mortality. To recommend protein intake liberalization in parallel with phosphate management by physicians may be a critical practice for better nutritional status and outcomes in HD patients.

DOI： 10.1053/j.jrn.2021.02.007

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Decreased serum magnesium levels are associated with mortality and fractures in patients with chronic kidney disease; however, there is no recommendation for Mg intake in these populations. This study used cross-sectional analysis to examine the association between Mg intake and serum Mg levels in patients undergoing hemodialysis. Sixty-one patients were included. The daily Mg intake was 185 mg (IQR: 151-203 mg), and serum Mg level was 2.4 mg/dL (IQR: 2.2-2.7 mg/dL). Multiple regression analysis showed that intake of enteral formulation by tube feeding was an independent factor associated with serum Mg level (B = 0.90 [95% confidence interval: 0.61-1.20], p < 0.01). These findings may aid in serum Mg level management through diet and enteral formulation in patients undergoing hemodialysis.

DOI： 10.1111/1744-9987.13760

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DOI： 10.1186/S41100-021-00383-3

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[Purpose] Muscle weakness in patients with chronic kidney disease is associated with several disease-related factors, and this study aimed to examine whether hemodialysis is one of risk factors for muscle weakness in patients with chronic kidney disease. [Participants and Methods] We conducted a cross-sectional study with 74 non-dialysis and 84 hemodialysis patients. Muscle strength evaluations were performed by measuring isometric knee extensor muscle strength and grip strength. Each evaluation item was compared between the hemodialysis and non-dialysis groups, and multiple regression analysis was performed to determine the factors associated with muscle strength. In addition, the correlation between lower-extremity muscle strength and grip strength was examined in each group. [Results] Isometric knee extensor muscle strength was significantly lower in the hemodialysis group than in the non-dialysis group. Grip strength was also significantly lower in the hemodialysis group than in the non-dialysis group. Hemodialysis was determined to be an independent risk factor associated with lower limb muscle strength as well as grip strength. The positive correlation between isometric knee extensor muscle strength and grip strength was almost the same in the groups. [Conclusion] Hemodialysis treatment was an independent risk factor for muscle weakness. Regular monitoring of grip strength may facilitate better management with physical therapy in hemodialysis patients.

DOI： 10.1589/jpts.33.742

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DOI： 10.1186/S41100-021-00352-W

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Uremic toxins are associated with various chronic kidney disease-related comorbidities. Indoxyl sulfate (IS), a protein-bound uremic toxin, reacts with vasculature, accelerating atherosclerosis and/or vascular calcification in animal models. Few studies have examined the relationship of IS with clinical outcomes in a large cohort of hemodialysis (HD) patients.


</sec>
<sec>
<title>Methods</title>
We included 1170 HD patients from the Japan Dialysis Outcomes and Practice Patterns Study Phase 5 (2012–15). We evaluated the associations of serum total IS (tIS) levels with all-cause mortality and clinical outcomes including cardiovascular (CV)-, infectious- and malignancy-caused events using Cox regressions.


</sec>
<sec>
<title>Results</title>
The median (interquartile range) serum tIS level at baseline was 31.6 μg/mL (22.6–42.0). Serum tIS level was positively associated with dialysis vintage. Median follow-up was 2.8 years (range: 0.01–2.9). We observed 174 deaths (14.9%; crude rate, 0.06/year). Serum tIS level was positively associated with all-cause mortality [adjusted hazard ratio per 10 μg/mL higher, 1.16; 95% confidence interval (CI) 1.04–1.28]. Association with cause-specific death or hospitalization events, per 10 μg/mL higher serum tIS level, was 1.18 (95% CI 1.04–1.34) for infectious events, 1.08 (95% CI 0.97–1.20) for CV events and 1.02 (95% CI 0.87–1.21) for malignancy events after adjusting for covariates including several nutritional markers.


</sec>
<sec>
<title>Conclusions</title>
In a large cohort study of HD patients, serum tIS level was positively associated with all-cause mortality and infectious events.


</sec>

DOI： 10.1093/ckj/sfaa121

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Protein-bound uremic toxins (PBUTs) are difficult to remove using conventional dialysis treatment owing to their high protein-binding affinity. As pH changes the conformation of proteins, it may be associated with the binding of uremic toxins. Albumin conformation at pH 2 to 13 was analyzed using circular dichroism. The protein binding behavior between indoxyl sulfate (IS) and albumin was examined using isothermal titration calorimetry. Albumin with IS, and serum with IS, p-cresyl sulfate, indole acetic acid or phenyl sulfate, as well as serum from hemodialysis patients, were adjusted pH of 3 to 11, and the concentration of the free PBUTs was measured using mass spectrometry. Albumin was unfolded at pH &lt; 4 or &gt;12, and weakened interaction with IS occurred at pH &lt; 5 or &gt;10. The concentration of free IS in the albumin solution was increased at pH 4.0 and pH 11.0. Addition of human serum to each toxin resulted in increased free forms at acidic and alkaline pH. The pH values of serums from patients undergoing hemodialysis adjusted to 3.4 and 11.3 resulted in increased concentrations of the free forms of PBUTs. In conclusion, acidic and alkaline pH conditions changed the albumin conformation and weakened the protein binding property of PBUTs in vitro.

DOI： 10.3390/toxins13020116

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Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate units that are linked by phosphoanhydride bonds and is involved in various pathophysiological processes. However, the role of polyP in immune cell dysfunction is not well-understood. In this study, using several biochemical and cell biology approaches, including cytokine assays, immunofluorescence microscopy, receptor-binding assays with quartz crystal microbalance, and dynamic light scanning, we investigated the effect of polyP on in vitro lipopolysaccharide (LPS)-induced macrophage inflammatory response. PolyP up-regulated LPS-induced production of the inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6, in macrophages, and the effect was polyP dose- and chain length-dependent. However, orthophosphate did not exhibit this effect. PolyP enhanced the LPS-induced intracellular macrophage inflammatory signals. Affinity analysis revealed that polyP interacts with LPS, inducing formation of small micelles, and the polyP-LPS complex enhanced the binding affinity of LPS to Toll-like receptor 4 (TLR4) on macrophages. These results suggest that inorganic polyP plays a critical role in promoting inflammatory response by enhancing the interaction between LPS and TLR4 in macrophages.

DOI： 10.1074/jbc.RA119.011763

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DOI： 10.1159/000500014

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© 2018 The Author(s). Background: High-circulating level of parathyroid hormone (PTH) is associated with elevated mortality in dialysis patients. The Japanese Society for Dialysis Therapy guideline suggests a lower PTH target than other international guidelines; thus, PTH control may differ in Japan compared with other regions, and be associated with mortality. Methods: We analyzed data from hemodialysis patients with ≥3 measurements of PTH during the first 9 months after enrollment in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4-5 (2009-2015). PTH control was assessed by the mean, slope, and mean squared error (MSE) of all PTH measurements over the 9-month run-in period. Distribution of each PTH control was assessed by regions (Europe/Australia/New Zealand [Eur/ANZ], Japan and North America) and dialysis vintage. Mortality rates were compared across PTH control categories using Cox regression models. Results: Mean PTH was lower in Japan than in other regions across dialysis vintage categories. In patients with dialysis vintage < 90 days, PTH level was more likely to decline > 5% per month in Japan (48% of patients) versus Eur/ANZ (35%) and North America (35%). In patients with dialysis vintage > 1 year, Japanese patients maintained steady PTH, while patients in Eur/ANZ and North America were more likely to experience a PTH increase. Mean PTH was associated with mortality in the overall samples (highest mortality rate for PTH > 600 pg/mL, hazard ratio, 1.35; 95% confidence interval, 1.20 to 1.52 vs PTH 200-399 pg/mL), and the association was obvious in the prevalent patients (hazard ratio, 1.44; 95% confidence interval, 1.26 to 1.65). PTH slope and MSE did not show significant association with mortality in the overall sample as well as in subjects stratified both by region and dialysis vintage. Conclusion: PTH control in hemodialysis patients, as measured by keeping a stable PTH level over 9 months, was observed in Japan contrasted with other regions. High PTH mean, but not increased PTH slope and MSE, was associated with mortality especially in prevalent patients.

DOI： 10.1186/s12882-018-1056-5

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

Uremic toxins are linked to chronic kidney disease (CKD)-related systemic diseases. β2-Microglobulin (β2-m), a water-soluble, middle-sized molecule, is associated with mortality and dialysis-related amyloidosis (DRA). DRA occurs in long-term dialysis patients, with β2-m amyloid deposited mainly in osteoarticular tissues. We investigated a model of β2-m amyloid fibril extension at neutral pH in the presence of trifluoroethanol or sodium dodecyl sulfate. Using this model, some biological molecules, including glycosaminoglycans and lysophospholipids, were found to be chaperones for β2-m amyloid fibril extension. Several protein-bound solutes, such as indoxyl sulfate (IS) and p-cresyl sulfate, are independent risk factors for cardiovascular disease in CKD patients, especially those undergoing dialysis. We investigated kidney injury-induced acceleration of atherosclerosis in association with macrophage phenotypic change to a proinflammatory state as well as increased IS deposition in lesions in an animal model. IS directly induced macrophage inflammation and impaired cholesterol efflux to high-density lipoprotein (HDL) in vitro. In addition, a clinical study showed that HDL isolated from CKD patients induced proinflammatory reactions and impaired cholesterol efflux to macrophages. These findings suggest that protein-bound solutes, including IS, will induce dysfunction of both macrophages and HDL in atherosclerotic lesions. To remove uremic toxins efficiently, we demonstrated the potential efficacy of oral charcoal adsorbent and hexadecyl-immobilized cellulose beads in hemodialysis patients. These findings suggest that uremic toxins induce various CKD-related systemic disorders, and further therapeutic strategies will be needed to reduce uremic toxins enough and improve life expectancy in CKD patients.

DOI： 10.1007/s10157-018-1588-9

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In chronic kidney disease (CKD) patients, accumulation of uremic toxins is associated with cardiovascular risk and mortality. One of the hallmarks of kidney disease-related cardiovascular disease is intravascular macrophage inflammation, but the mechanism of the reaction with these toxins is not completely understood. Macrophages differentiated from THP-1 cells were exposed to indoxyl sulfate (IS), a representative uremic toxin, and changes in inflammatory cytokine production and intracellular signaling molecules including interleukin (IL)-1, aryl hydrocarbon receptor (AhR), nuclear factor (NF)-κ, and mitogen-activated protein kinase (MAPK) cascades as well as the NLRP3 inflammasome were quantified by real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay. IS induced macrophage pro-IL-1β mRNA expression, although mature IL-1 was only slightly increased. IS increased AhR and the AhR-related mRNA expression
this change was suppressed by administration of proteasome inhibitor. IS promoted phosphorylation of NF-κB p65 and MAPK enzymes
the reaction and IL-1 expression were inhibited by BAY11-7082, an inhibitor of NF-κB. In contrast, IS decreased NLRP3 and did not change ASC, pro-caspase 1, or caspase-1 activation. IS-inducing inflammation in macrophages results from accelerating AhR-NF-κB/MAPK cascades, but the NLRP3 inflammasome was not activated. These reactions may restrict mature IL-1β production, which may explain sustained chronic inflammation in CKD patients.

DOI： 10.3390/toxins10030124

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/aor.12961

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

Patients with chronic kidney disease (CKD), especially those on dialysis treatment, are at high risk of bone fracture. In CKD-mineral and bone disorder (CKD-MBD), secondary hyperparathyroidism in patients with advanced CKD induces bone abnormalities, and skeletal resistance to parathyroid hormone (PTH) starts in the early stages of kidney disease. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate reduce the expression of PTH receptor as well as PTH-induced cyclic adenosine 3',5' monophosphate production in osteoblasts. CKD also impairs bone strength, especially quality. In a rat model, kidney damage reduces the bone-storage modulus and changes the cortical bone chemical composition with or without hyperparathyroidism. The oral charcoal adsorbent AST-120 improves CKD-induced bone abnormalities as blood levels of indoxyl sulfate decrease. Uremic osteoporosis, a new concept of CKD-related bone fragility, is a main cause of CKD-induced bone abnormalities, particularly impaired bone quality. There is limited information about the effect and safety of anti-osteoporotic drugs for patients with CKD, especially those on dialysis, but the use of AST-120 and renin-angiotensin system inhibitors may modulate bone quality and decrease the incidence of fracture. Thus, the management of CKD-MBD plus use of other therapeutic interventions for uremic osteoporosis is necessary to prevent bone fragility in patients with CKD.

DOI： 10.1007/s40620-017-0406-x

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DOI： 10.1142/9919

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A 36-year-old woman who was undergoing dialysis for end-stage kidney disease (ESKD) was admitted to our hospital with consciousness disorder. She was diagnosed with Budd-Chiari syndrome due to antiphospholipid syndrome at the age of 28 years. Her kidney function and leg edema gradually deteriorated. After initiation of hemodialysis (HD), transient loss of consciousness due to hepatic encephalopathy during HD treatment occurred frequently. Her kidney replacement therapy was changed to online hemodiafiltration (HDF), which dramatically improved her hepatic coma. Compared with HD, HDF contributed to the increase in Fischer's ratio and decrease in tryptophan level, which has a high protein-bound property. This case suggests that HDF may be beneficial for hepatic encephalopathy in ESKD patients by modulating the amino acid profile.

DOI： 10.1007/s13730-015-0209-7

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The macrophage and its related cholesterol efflux are considered to be a key player in atherosclerotic formation in relation to the function of high-density lipoprotein (HDL). The HDL function can be evaluated by the reaction between lipid-loaded macrophages and lipid-acceptors in the HDL fraction from the plasma, apolipoprotein B-depleted serum, and/or whole serum/plasma. Recent studies have reported that an impaired cholesterol efflux of HDL is observed in patients with cardiometabolic diseases, such as dyslipidemia, diabetes mellitus, and chronic kidney disease. A population-based cohort study has reported an inverse association between the cholesterol efflux capacity of HDL and the incidence of atherosclerotic disease, regardless of the serum HDL-cholesterol level. Moreover, in this paper, when we summarized several clinical interventional studies of statin treatment that examined cholesterol efflux, a potential increase in the efflux in patients treated with statins was implied. However, the effect was not fully defined in the current situation because of the small sample sizes, lack of a unified protocol for measuring the efflux, and short-term intervention periods without cardiovascular outcomes in available studies. Further investigation is necessary to determine the effect of drugs on cholesterol efflux. With additional advanced studies, cholesterol efflux is a promising laboratory index to understand the HDL function. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.cca.2016.04.012

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Objective: Chronic kidney disease (CKD) amplifies atherosclerosis, which involves renin-angiotensin system (RAS) regulation of macrophages. RAS influences peroxisome proliferator-activated receptor-g (PPAR gamma), a modulator of atherogenic functions of macrophages, however, little is known about its effects in CKD. We examined the impact of combined therapy with a PPARg agonist and angiotensin receptor blocker on atherogenesis in a murine uninephrectomy model.
Methods: Apolipoprotein E knockout mice underwent uninephrectomy (UNx) and treatment with pioglitazone (UNx + Pio), losartan (UNx + Los), or both (UNx + Pio/Los) for 10 weeks. Extent and characteristics of atherosclerotic lesions and macrophage phenotypes were assessed; RAW264.7 and primary peritoneal mouse cells were used to examine pioglitazone and losartan effects on macrophage phenotype and inflammatory response.
Results: UNx significantly increased atherosclerosis. Pioglitazone and losartan each significantly reduced the atherosclerotic burden by 29.6% and 33.5%, respectively; although the benefit was dramatically augmented by combination treatment which lessened atherosclerosis by 55.7%. Assessment of plaques revealed significantly greater macrophage area in UNx + Pio/Los (80.7 +/- 11.4% vs. 50.3 +/- 4.2% in UNx + Pio and 57.2 +/- 6.5% in UNx + Los) with more apoptotic cells. The expanded macrophage-rich lesions of UNx + Pio/Los had more alternatively activated, Ym-1 and arginine 1-positive M2 phenotypes (Ym-1: 33.6 +/- 8.2%, p &lt; 0.05 vs. 12.0 +/- 1.1% in UNx; arginase 1: 27.8 +/- 0.9%, p &lt; 0.05 vs. 11.8 +/- 1.3% in UNx). In vitro, pioglitazone alone and together with losartan was more effective than losartan alone in dampening lipopolysaccharide-induced cytokine production, suppressing M1 phenotypic change while enhancing M2 phenotypic change.
Conclusion: Combination of pioglitazone and losartan is more effective in reducing renal injury-induced atherosclerosis than either treatment alone. This benefit reflects mitigation in macrophage cytokine production, enhanced apoptosis, and a shift toward an anti-inflammatory phenotype. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2015.06.055

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Accumulation of protein-bound uraemic toxins (PBUTs) is one of the reasons for the development of uraemia-related complications including cardiovascular disease; however, conventional haemodialysis is limited in its ability to remove PBUTs. We aimed to examine whether the oral charcoal adsorbent AST-120 has an additive effect on PBUT removal in haemodialysis patients. During the 4-week study, anuric patients undergoing haemodialysis received AST-120 (6 g/day) in the last 2 weeks (n=10) or the first 2 weeks (n=10). Serum levels of total and free PBUTs such as indoxyl sulfate, p-cresyl sulfate, and phenyl sulfate at the pre- and postdialysis sessions were measured before and after AST-120 use and after discontinuation. Levels of the oxidative stress markers oxidized albumin and 8-isoprostane were also measured. AST-120 use induced dramatic reduction of indoxyl sulfate (total, 45.7% [33.2-50.5%]; free, 70.4% [44.8-79.8%]), p-cresyl sulfate (total, 31.1% [25.0-48.0%]; free, 63.5% [49.3-70.9%]), and phenyl sulfate (free, 50.6% [32.3-71.2%]) levels; however, this effect disappeared after the discontinuation of AST-120. AST-120 use also induced substantial reduction of the oxidized albumin and 8-isoprostane levels. In conclusion, oral administration of AST-120 had additive effects on the continuous reduction of some PBUTs in anuric patients undergoing haemodialysis.

DOI： 10.1038/srep14381

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One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1 beta, IS 1.0 mM: 101.8 +/- 21.8 pg/mL vs. 0 mM: 7.0 +/- 0.3 pg/mL, TNF-alpha, IS 1.0 mM: 96.6 +/- 11.0 pg/mL vs. 0 mM: 15.1 +/- 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% +/- 7.3% vs. 0 mM: 43.5% +/- 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.

DOI： 10.3390/toxins7083155

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Background
Few risk scores are available for predicting mortality in chronic kidney disease (CKD) patients undergoing predialysis nephrology care. Here, we developed a risk score using predialysis nephrology practice data to predict 1-year mortality following the initiation of haemodialysis (HD) for CKD patients.
Methods
This was a multicenter cohort study involving CKD patients who started HD between April 2006 and March 2011 at 21 institutions with nephrology care services. Patients who had not received predialysis nephrology care at an estimated glomerular filtration rate (eGFR) of approximately 10 mL/min per 1.73 m(2) were excluded. Twenty-nine candidate predictors were selected, and the final model for 1-year mortality was developed via multivariate logistic regression and was internally validated by a bootstrapping technique.
Results
A total of 688 patients were enrolled, and 62 (9.0%) patients died within one year of HD initiation. The following variables were retained in the final model: eGFR, serum albumin, calcium, Charlson Comorbidity Index excluding diabetes and renal disease (modified CCI), performance status (PS), and usage of erythropoiesis-stimulating agent (ESA). Their beta-coefficients were transformed into integer scores: three points were assigned to modified CCI &gt;= 3 and PS 3-4; two to calcium&gt;8.5 mg/dL, modified CCI 1-2, and no use of ESA; and one to albumin&lt;3.5 g/dL, eGFR&gt;7 mL/min per 1.73 m(2), and PS 1-2. Predicted 1-year mortality risk was 2.5% (score 0-4), 5.5% (score 5-6), 15.2% (score 7-8), and 28.9% (score 9-12). The area under the receiver operating characteristic curve was 0.83 (95% confidence interval, 0.79-0.89).
Conclusions
We developed a simple 6-item risk score predicting 1-year mortality after the initiation of HD that might help nephrologists make a shared decision with patients and families regarding the initiation of HD.

DOI： 10.1371/journal.pone.0129180

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

Background
Patients with chronic kidney disease, especially those undergoing dialysis treatment and having secondary hyperparathyroidism, have a high risk of bone fracture. The renin-angiotensin system (RAS) is associated with osteoclastic bone resorption. We aimed to examine whether the use of RAS inhibitors reduces the incidence of fracture in hemodialysis patients.
Methods and Findings
This was a multicenter, 3-year, prospective, observational study. From 2008 to 2011, maintenance hemodialysis patients with secondary hyperparathyroidism (N = 3,276) treated with angiotensin converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) at baseline were followed for a mean of 2.7 years. The association between the use of ACEI/ARB and hospitalization rate owing to fracture was examined by using Cox regression models. Effect modifications by the severity of secondary hyperparathyroidism (intact parathyroid hormone [iPTH] level), sex, and systolic blood pressure were also examined. The incidence proportion of fracture-related hospitalization was 5.42% throughout the observation period. ACEI/ARB use was associated with a lower rate of fracture-related hospitalization (adjusted hazard ratio, 0.65; 95% confidence interval [CI], 0.45-0.92). This association was not significantly affected by sex (P = 0.56) or systolic blood pressure levels (P = 0.87). The hazard ratios adjusted by iPTH levels were qualitatively different, but not statistically significant (P = 0.11): 0.77 (95% CI, 0.42-1.39), 0.38 (95% CI, 0.20-0.73), 0.59 (95% CI, 0.29-1.21), and 1.29 (95% CI, 0.58-2.42) for the first, second, third and fourth quartiles of iPTH, respectively.
Conclusions
Use of RAS inhibitors is associated with a lower rate of fracture-related hospitalization in hemodialysis patients with secondary hyperparathyroidism.

DOI： 10.1371/journal.pone.0122691

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Authorship：Lead author   Language：English   Publisher：SPRINGER  

Traditional risk factors do not account for increased cardiovascular disease in patients with chronic kidney disease (CKD), particularly individuals whose CKD has progressed to end-stage kidney disease requiring dialysis. CKD patients on dialysis show little to no cardiovascular benefits from lipid-lowering therapy and thus have an exaggerated residual cardiovascular risk. High density lipoprotein (HDL) quantity and functionality may explain some of the residual risk. CKD affects the composition and disrupts the functionality of HDL, including cholesterol acceptor function and inflammatory effects. Notably, although these HDL abnormalities prevail in CKD, they do not track together and thereby support the idea of separate and distinct mechanistic pathways for each critical function of HDL. Targeting individual perturbations in HDL function represents a novel approach to therapy in this population.

DOI： 10.1007/s10157-013-0857-x

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A fragility fracture is a serious complication in patients with diabetes mellitus as a result of hyperglycaemia, insulin resistance and the production of AGEs (advanced glycation end-products). In their paper published in the Biochemical Journal, Bartolomé et al. identified a role for autophagy in the differentiation, function and survival of osteoblastic cells in a high-glucose environment, and they also demonstrated that osteoblastic cell survival was limited by chemical and genetic inhibition of autophagy. These novel findings show the possibility of investigating a therapeutic strategy of maintaining autophagy in osteoblasts to lead to the prevention of diabetes-related osteopaenia. Autophagy is one of the common functions for maintaining cellular health, and the regulation of autophagy that is perturbed by diabetes mellitus may induce improvement of cellular functions not only for diabetes-related osteopaenia, but also for other systemic complications. However, systemic activation of autophagy may not always induce beneficial effects for non-targeted healthy cells, and autophagy should be controlled at a proper level at each disease stage in each target organ.

DOI： 10.1042/BJ20131282

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Objectives This study examined the functionality of high-density lipoprotein (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD).
Background The high rate of cardiovascular disease (CVD) in chronic kidney disease is not explained by standard risk factors, especially in patients with ESRD-HD who appear resistant to benefits of statin therapy. HDL is antiatherogenic because it extracts tissue cholesterol and reduces inflammation.
Methods Cellular cholesterol efflux and inflammatory response were assessed in macrophages exposed to HDL of patients with ESRD-HD or controls.
Results HDL from patients with ESRD-HD was dramatically less effective than normal HDL in accepting cholesterol from macrophages (median 6.9%; interquartile range [IQR]: 1.4% to 10.2%) versus control (median 14.9%; IQR: 9.8% to 17.8%; p &lt; 0.001). The profound efflux impairment was also seen in patients with ESRD-HD and diabetes compared with patients with diabetes without renal disease (median 8.1%; IQR: 3.3% to 12.9%) versus control (median 13.6%; IQR: 11.0% to 15.9%; p = 0.009). In vitro activation of cellular cholesterol transporters increased cholesterol efflux to both normal and uremic HDL. HDL of patients with ESRD-HD had reduced anti-chemotactic ability and increased macrophage cytokine response (tumor necrosis factor-alpha, interleukin-6, and interleukin-1-beta). HDL of patients with ESRD-HD on statin therapy had reduced inflammatory response while maintaining impaired cholesterol acceptor function. Interestingly, impaired HDL-mediated efflux did not correlate with circulating C-reactive protein levels or cellular inflammatory response.
Conclusions These findings suggest that abnormal HDL capacity to mediate cholesterol efflux is a key driver of excess CVD in patients on chronic hemodialysis and may explain why statins have limited effect to decrease CV events. The findings also suggest cellular cholesterol transporters as potential therapeutic targets to decrease CV risk in this population. (J Am Coll Cardiol 2012;60:2372-9) (C) 2012 by the American College of Cardiology Foundation

DOI： 10.1016/j.jacc.2012.09.013

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Part of collection (book)   Publisher：John Wiley and Sons  

DOI： 10.1002/9781118424032.ch16

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective-Angiotensin II is a major determinant of atherosclerosis. Although macrophages are the most abundant cells in atherosclerotic plaques and express angiotensin II type 1 receptor (AT1), the pathophysiologic role of macrophage AT1 in atherogenesis remains uncertain. We examined the contribution of macrophage AT1 to accelerated atherosclerosis in an angiotensin II-responsive setting induced by uninephrectomy (UNx).
Methods and Results-AT1(-/-) or AT1(+/+) marrow from apolipoprotein E deficient (apoE(-/-)) mice was transplanted into recipient apoE-/- mice with subsequent UNx or sham operation: apoE(-/-)/AT1(+/+) -&gt; 3apoE(-/-) +sham; apoE(-/-)/AT1(+/+) 3apoE(-/-) +UNx; apoE(-/-)/AT1(-/-) -&gt; 3apoE(-/-) +sham; apoE(-/-)/AT1(-/-) -&gt; 3apoE(-/-) +UNx. No differences in body weight, blood pressure, lipid profile, and serum creatinine were observed between the 2 UNx groups. ApoE(-/-)/AT1(+/+) 3apoE(-/-) +UNx had significantly more atherosclerosis (16907 +/- 21473 versus 116071 +/- 8180 mu m(2), P &lt; 0.05). By contrast, loss of macrophage AT1 which reduced local AT1 expression, prevented any effect of UNx on atherosclerosis (77174 +/- 9947 versus 75714 +/- 11333 mu m(2), P = NS). Although UNx did not affect total macrophage content in the atheroma, lesions in apoE(-/-)/AT1(-/-) 3apoE(-/-) +UNx had fewer classically activated macrophage phenotype (M1) and more alternatively activated phenotype (M2). Further, UNx did not affect plaque necrosis or apoptosis in apoE(-/-)/AT1(-/-) 3apoE(-/-) whereas it significantly increased both (by 2- and 6-fold, respectively) in apoE(-/-)/AT1(+/+) 3apoE(-/-) mice. Instead, apoE(-/-)/AT1(-/-) 3apoE(-/-) had 5-fold-increase in macrophage-associated apoptotic bodies, indicating enhanced efferocytosis. In vitro studies confirmed blunted susceptibility to apoptosis, especially in M2 macrophages, and a more efficient phagocytic function of AT1(-/-) macrophages versus AT1(+/+).
Conclusion-AT1 receptor of bone marrow-derived macrophages worsens the extent and complexity of renal injury-induced atherosclerosis by shifting the macrophage phenotype to more M1 and less M2 through mechanisms that include increased apoptosis and impaired efferocytosis. (Arterioscler Thromb Vasc Biol. 2011;31:2856-2864.)

DOI： 10.1161/ATVBAHA.111.237198

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Background. Accelerated atherosclerosis and increased cardiovascular events are not only more common in chronic kidney disease (CKD) but are more resistant to therapeutic interventions effective in the general population. The oral charcoal adsorbent, AST-120, currently used to delay start of dialysis, reduces circulating and tissue uremic toxins, which may contribute to vasculopathy, including atherosclerosis. We, therefore, investigated whether AST-120 affects CKD-induced atherosclerosis.
Methods. Apolipoprotein E-deficient mice, a model of atherosclerosis, underwent uninephrectomy, subtotal nephrectomy or sham operation at 8 weeks of age and were treated with AST-120 after renal ablation. Atherosclerosis and its characteristics were assessed at 25 weeks of age.
Results. Uninephrectomy and subtotal nephrectomised mice had significantly increased acceleration of atherosclerosis. AST-120 treatment dramatically reduced the atherosclerotic burden in mice with kidney damage, while there was no beneficial effect in sham-operated mice. The benefit was independent of blood pressure, serum total cholesterol or creatinine clearance. AST-120 significantly decreased necrotic areas and lessened aortic deposition of the uremic toxin indoxyl sulfate without affecting lesional macrophage or collagen content. Furthermore, AST-120 lessened aortic expression of monocyte chemoattractant protein-1, tumor necrosis factor-alpha and interleukin-1 beta messenger RNA.
Conclusions. AST-120 lessens the extent of atherosclerosis induced by kidney injury and alters lesion characteristics in apolipoprotein E-deficient mice, resulting in plaques with a more stable phenotype with less necrosis and reduced inflammation.

DOI： 10.1093/ndt/gfq759

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Dialysis-Related Amyloidosis (DRA) is a general amyloidosis, which is specifically found in CKD stage 5 patients. DRA causes various osteoarticular lesions in dialysis patients, and therefore it is not practical to regard this condition separately from chronic kidney disease-mineral and bone disorder (CKD-MBD), at least from the viewpoint of daily clinical practice. However, it is still controversial whether this disease condition should be included in CKD-MBD.
Recently, a better understanding of the pathogenesis of DRA has been obtained by examination of beta(2)-microglobullin-related amyloid fibril formation, extension, and depolymerization in vitro. Apoliprotein E, proteoglycans, and glycosaminoglycans stabilize the amyloid fibrils. in addition, some lysophospholipids and non-esterified fatty acids accelerate amyloid fibril formation and extension under physiological conditions in vitro. Those molecules may enhance the amyloid deposition in vivo.
The frequency and severity of osteoarticular disorders that may be associated with DRA accelerate with the duration of dialysis therapy. We have shown that patients undergoing dialysis therapy for 30 years or more survive with serious complications from osteoarticular disorders. DRA is one of the most harmful osteoarticular complications with regard to the maintenance of daily activities and quality of life in patients undergoing long-term dialysis therapy, in addition to the classical complications of CKD-MBD. (c) 2009 Published by Elsevier Inc.

DOI： 10.1016/j.bone.2009.03.655

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Authorship：Lead author   Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Purpose of review
Patients with chronic kidney disease (CKD) have the highest risk for atherosclerotic cardiovascular disease (CVD). Current interventions have been insufficiently effective in lessening excess incidence and mortality from CVD in patients with CKD versus other high-risk groups. This review focuses on traditional and CKD-related risks as well as key mechanisms of macrophage foam cell formation that underlie the excess CVD in the setting of CKD.
Rent findings
Hyperlipidemia, particularly increased low-density lipoprotein (LDL) cholesterol, is the key factor in atherogenesis in the general population, but has not been found to be the overriding risk for greater CVD in CKD, especially as renal damage progresses. Although higher incidence of CVD in CKD is not due to higher serum lipids per se, CKD is associated with abnormal lipid metabolism that is proatherogenic. CKD-related risks, including inflammation and disturbances in mineral metabolism, have been implicated. In addition, perturbations of the macrophage, a cell that is central in atherogenesis, may be important.
Summary
The mechanisms underlying the heightened risk for CVD in CKD have been the focus of intense study and may relate to the combined effects of traditional and CKD-specific risks involving inflammation and lipid metabolism, especially perturbation of macrophage cholesterol homeostasis.

DOI： 10.1097/MNH.0b013e328327b360

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：DUSTRI-VERLAG DR KARL FEISTLE  

Aims: Increasing numbers of patients are undergoing long-term dialysis therapy. It is crucial for their quality of life to overcome dialysis-related complications, such as dialysis-related amyloidosis (DRA) and other osteoarticular disorder. The aim of the study was to investigate the characteristics, such as dialysis-related complications, in chronic kidney disease (CKD) Stage 5D patients undergoing dialysis therapy for more than 30 years or more. Methods: From 2003 to 2006, 359 CKD Stage 5D patients who were admitted to a single tertiary-care center. The age and the duration of dialysis therapy, the purpose for hospital admission, and history of osteoarticular disorder, such as carpal tunnel syndrome (CTS), destructive spondyloarthropathy (DSA) and joint arthropathy, were studied. Results: The proportions of the patients undergoing dialysis therapy for 20 - 24, 25 - 29 years and 30 years or more were 8.9, 5.6, and 4.5% of all admitted patients, respectively. DSA was a major cause of hospital admissions in long-term dialysis patients, especially in those treated for 30 years or more. The rate of surgery for osteoarticular disorder, such as CTS, DSA and joint arthropathy, which may show the presence of DRA, was 25.0, 66.0 and 77.8% in 20 - 24 years, 25 - 29 years and 30 years or more after the initiation of dialysis therapy, respectively. The frequency and severity of osteoarticular disorder accelerated with the duration of dialysis therapy, especially in those treated for 30 years or more. The rate of parathyroidectomy for secondary hyperparathyroidism was performed for 37.5% in 22.1 +/- 2.1 years after the initiation of dialysis treatment in the patients treated for 30 years or more. Mean age at the initiation of dialysis therapy was 27.3 +/- 8.0 years, and primary cause of CKD was mainly chronic glomerulonephritis in the patients undergoing dialysis therapy for 30 years or more. Conclusion: CKD stage 5D patients undergoing dialysis therapy for 30 years or more survive with characteristics of younger age at initiation of dialysis therapy, chronic glomerulonephritis as a primary cause of CKD, and serious complication of osteoarticular disorders.

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Dialysis-related amyloidosis (DRA) is a frequent and serious complication in patients on long-term dialysis. The amyloid has a marked affinity for joint tissues, and carpal tunnel syndrome, polyarthralgia, destructive spondyloarthropathy, and bone cysts are the major clinical manifestations of DRA. 2-Microglobulin (beta(2)-m) was identified as the major protein constituent of the amyloid fibrils. Risk factors for the development of DRA include age, duration of dialysis treatment, use of low-flux dialysis membrane, use of low purity dialysate, monocyte chemoattractant protein-1 GG genotype, and apolipoprotein E4 allele, although the retention Of beta(2)-m in the plasma appears to be prerequisite. Clinical therapeutic strategies for DRA include dialysis, medical or surgical therapy, and renal transplantation. Preventive measures have attempted to remove beta(2)-m from the serum by using high-flux membranes and a beta(2)-m adsorption column in hemodialysis. Renal transplantation is a radical approach to treating the arthralgias attributed to the amyloid deposits while the regression of dialysi-related amyloid deposits is not identified after successful renal transplantation in many studies. It is necessary to elucidate the pathogenesis of DRA and to establish more effective prevention and therapy in the future. (c) 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bbapap.2005.09.006

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DOI： 10.1016/j.bbapap.2005.07.007

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

In 2-microglobulin-related (Abeta2M) amyloidosis, partial unfolding of beta(2)-microglobulin (beta(2)-m) is believed to be prerequisite to its assembly into Abeta(2)M amyloid fibrils in vivo. Although low pH or 2,2,2-trifluoroethanol at a low concentration has been reported to induce partial unfolding of beta2-m and subsequent amyloid fibril formation in vitro, factors that induce them under near physiological conditions have not been determined. Using fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy, we here show that at low concentrations, sodium dodecyl sulfate (SDS) converts natively folded beta2-m monomers into partially folded, alpha-helix-containing conformers. Surprisingly, this results in the extension of Abeta2M amyloid fibrils at neutral pH, which could be explained basically by a first-order kinetic model. At low concentrations, SDS also stabilized the fibrils at neutral pH. These SDS effects were concentration-dependent and maximal at approximately 0.5 mM, around the critical micelle concentration of SDS (0.67 mM). As the concentration of SDS was increased above 1 mM, the alpha-helix content of beta2-m rose to approximately 10%, while the beta-sheet content decreased to approximately 20%, a change paralleled by a complete cessation of fibril extension and the destabilization of the fibrils. Detergents of other classes had no significant effect on the extension of fibrils. These findings are consistent with the hypothesis that in vivo, specific factors (e.g., phospholipids) that affect the conformation and stability of beta2-m and amyloid fibrils will have significant effects on the kinetics of Abeta2M fibril formation.

DOI： 10.1021/bi049262u

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beta(2)-Microglobulin-related (Abeta2M) amyloidosis is a frequent and serious complication in patients on long-term dialysis, and beta(2)-microglobulin is a major structural component of Abeta2M amyloid fibrils. Several biologic molecules inhibiting the depolymerization of Abeta2M amyloid fibrils at a neutral pH were found recently. The effect of trifluoroethanol and glycosaminoglycans (GAG) on the extension of the fibrils at a neutral pH was investigated with the use of fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy. Trifluoroethanol at concentrations of up to 20% (vol/vol) caused fibril extension of heparin-stabilized seeds, inducing a subtle change in the tertiary structure of beta(2)-microglobulin and stabilizing the fibrils at a neutral pH. This extension reaction followed a first-order kinetic model. In addition, some GAG, especially heparin, dose-dependently enhanced the fibril extension. These results suggest that some GAG, especially heparin, may bind to the fibrils and enhance their deposition in vivo. Thus, the experimental system described here should be useful to search for the factors that accelerate Abeta2M amyloid deposition in vivo. In addition, the interference of the binding of GAG to Abeta2M amyloid fibrils may be an attractive therapeutic modality.

DOI： 10.1097/01.ASN.0000103228.81623.C7

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Objective: Although early reports demonstrated that serum beta(2)-Microglobulin (s-beta(2)m) concentrations in patients on peritoneal dialysis (PD) were lower than those in patients on hemodialysis (HD), more recent studies demonstrated lower s-beta(2)M concentrations in HD patients treated mainly with high-flux synthetic membranes. We therefore compared s-beta(2)m concentrations between patients on PD and on HD, and also analyzed the relationship between s-beta(2)m concentrations and other parameters in patients on PD.
Patients and Methods: We investigated 24 patients who had been undergoing PD [11 on continuous ambulatory peritoneal dialysis, 13 on continuous cycling peritoneal dialysis] for 4.3 +/- 2.7 years, and 24 patients who had been undergoing HD with high-flux synthetic membranes for 6.1 +/- 3.2 years. Concentrations Of s-beta(2)m in the PD patients were compared to concentrations in the HD patients. In patients on PD, we also analyzed the relationship between s-beta(2)m concentration and other parameters, including residual renal function, total weekly Kt/V urea, total weekly creatinine clearance (CCr), and dialysis schedules.
Results: We found no significant difference in s-beta(2)m concentrations between the PD and HD patients (33.6 +/- 10.4 mg/L vs 30.3 +/- 10.5 mg/L respectively). Concentrations of s-beta(2)m in PD patients rose with PD duration and were significantly inversely correlated with residual renal function (r = -0.71, p &lt; 0.0001). Unexpectedly, concentrations of s-&beta;(2)m In anuric PD patients rose as peritoneal CCr increased. And most of the patients with high s-&beta;(2)m levels fell into the high or high-average transport categories according to a peritoneal equilibration test.
Conclusions: Concentrations of s-&beta;(2)m in patients on PD did not differ significantly from concentrations in HD patients who were using high-flux synthetic membranes. The contribution of residual renal function to removal of &beta;(2)m Was more important than the contribution of peritoneal clearance. High peritoneal clearance of small molecules did not result in low s-&beta;(2)m concentrations, especially in anuric patients with accelerated peritoneal permeability.

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DOI： 10.1007/s10157-024-02481-y

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DOI： 10.1007/S00774-024-01500-Y

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From a physicochemical viewpoint, amyloid fibril formation is a phase transition from soluble to crystal-like sates limited by supersaturation. It occurs only above solubility (i.e., the solubility limit) coupled with a breakdown of supersaturation. Although many studies have examined the role of molecular chaperones in the context of proteostasis, the role of supersaturation has not been addressed. Moreover, although molecular chaperone-dependent disaggregations have been reported for preformed amyloid fibrils, amyloid fibrils will not dissolve above the solubility of monomers, even if agitations fragment long fibrils to shorter amyloid particles. On the other hand, on considering a reversible and coupled equilibrium of interactions, folding/unfolding and amyloid formation/disaggregation, molecules stabilizing native states can work as a disaggregase reversing the amyloid fibrils to monomers. It is likely that the proteostasis network has various intra- and extracellular components which disaggregate preformed amyloid fibrils as well as prevent amyloid formation. Further studies with a view of solubility and supersaturation will be essential for comprehensive understanding of proteostasis.

DOI： 10.1016/j.jmb.2024.168475

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DOI： 10.1080/13506129.2024.2315148

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DOI： 10.2139/ssrn.4589844

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Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independent of its effect to suppress parathyroid hormone (PTH). We analyzed the association between prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3-6 (2005-2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed vs. not prescribed active vitamin D was 1.02 (0.90-1.17) for any fracture and 1.00 (0.81-1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher vs. lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. This article is protected by copyright. All rights reserved.

DOI： 10.1002/jbmr.4913

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The combination of systemic amyloid A (AA) amyloidosis and xanthogranulomatous pyelonephritis (XGP) resulting from a chronic urinary tract infection is extremely rare. We herein report a case of systemic AA amyloidosis secondary to XGP for which clinical remission developed after nephrectomy. To our knowledge, this is the first case report describing the clinical improvement of systemic AA amyloidosis secondary XGP after nephrectomy in Japan. Clinicians should be aware of this uncommon combination and search for amyloid depositions in cases of XGP.

DOI： 10.2169/internalmedicine.1806-23

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Sodium magnetic resonance imaging can non-invasively assess sodium distribution, specifically sodium concentration in the countercurrent multiplication system in the kidney, which forms a sodium concentration gradient from the cortex to the medulla, enabling efficient water reabsorption. This study aimed to investigate whether sodium magnetic resonance imaging can detect changes in sodium concentrations under normal conditions in mice and in disease models such as a mouse model with diabetes mellitus. Methods: We performed sodium and proton nuclear magnetic resonance imaging using a 9.4-T vertical standard-bore super-conducting magnet. Results: A condition of deep anesthesia, with widened breath intervals, or furosemide administration in 6-week-old C57BL/6JJcl mice showed a decrease in both tissue sodium concentrations in the medulla and sodium concentration gradients from the cortex to the medulla. Further, sodium magnetic resonance imaging revealed reductions in the sodium concentration of the medulla and in the gradient from the cortex to the medulla in BKS.Cg-Leprdb+/+ Leprdb/Jcl mice at very early type-2 diabetes mellitus stages compared to corresponding control BKS.Cg-m+/m+/Jcl mice. Conclusions: The kidneys of BKS.Cg-Leprdb+/+ Leprdb/Jcl mice aged 6 weeks showed impairments in the countercurrent multiplication system. We propose the utility of 23Na MRI for evaluating functional changes in diabetic kidney disease, not as markers that reflect structural damage. Thus, 23Na MRI may be a potential very early marker for structures beyond the glomerulus; this may prompt intervention with novel efficacious tubule-targeting therapies.

DOI： 10.34067/KID.0000000000000072

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BACKGROUND: The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied. METHODS: We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP. RESULTS: Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06-11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Cardiac disfunctions were significantly associated with the high hANP level. CONCLUSIONS: The hANP level is indicative of both fluid volume and cardiac dysfunction. A threshold hANP level of 100 pg/mL can serve as a predictive marker for AHF and a practical indicator for volume control.

DOI： 10.1007/s10157-023-02333-1

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BACKGROUND: Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients. METHODS: We included 42,319 chronic in-centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2-6 (2002-2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months. RESULTS: Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450-600, 300-450, 150-300, 50-150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150-299 pg/mL was -0.60%, -0.12%, -0.10%, +0.15%, and +0.35% for PTH ≥600, 450-600, 300-450, 50-150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow-up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6-1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9-13%] shorter lifespan, and 18% (95% CI, 14-23%) of this effect was mediated through weight loss ≥2.5%. CONCLUSIONS: Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH-lowering therapy can limit weight loss and improve longer term dialysis outcomes.

DOI： 10.1002/jcsm.12722

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DOI： 10.1093/ndt/gfaa319

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Background</title>
Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear.


</sec>
<sec>
<title>Methods</title>
Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils.


</sec>
<sec>
<title>Results</title>
Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3–30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients.


</sec>
<sec>
<title>Conclusions</title>
These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.


</sec>

DOI： 10.1093/ndt/gfaa223

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Chronic kidney disease (CKD) is associated with a high incidence of fractures. However, the pathophysiology of this disease is not fully understood, and limited therapeutic interventions are available. This study aimed to determine the impact of type-1 angiotensin II receptor blockade (AT-1RB) on preventing CKD-related fragility fractures and elucidate its pharmacological mechanisms. AT-1RB use was associated with a lower risk of hospitalization due to fractures in 3276 patients undergoing maintenance hemodialysis. In nephrectomized rats, administration of olmesartan suppressed osteocyte apoptosis, skeletal pentosidine accumulation and apatite disorientation, and partially inhibited the progression of the bone elastic mechanical properties, while the bone mass unchanged. Olmesartan suppressed angiotensin II-dependent oxidation stress and apoptosis in primary cultured osteocytes in vitro. In conclusion, angiotensin II-dependent intraskeletal oxidation stress deteriorated the bone elastic mechanical properties by promoting osteocyte apoptosis and pentosidine accumulation. Thus, AT-1RB contributes to the underlying pathogenesis of abnormal bone quality in the setting of CKD, possibly by oxidative stress.

DOI： 10.1002/jbmr.4159

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ekir.2020.08.013

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BACKGROUND: In patients with chronic kidney disease (CKD), dysbiosis in the gastrointestinal microbiome is thought to be associated with increased production of uremic toxins, such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Sucroferric oxyhydroxide (SFO), an iron-based phosphate binder, may affect the gastrointestinal microbiome and the production of uremic toxins. We aimed to examine whether SFO administration affected distribution of gastrointestinal microbiome and serum uremic toxin levels in CKD patients undergoing hemodialysis. METHODS: In this single-center, open-label, interventional study, 18 maintenance hemodialysis patients with hyperphosphatemia were prescribed with SFO. We collected serum samples before and after 3 months of administration, and serum levels of IS and PCS were measured. A control group of 20 hemodialysis patients without SFO was evaluated. We evaluated gastrointestinal microbiome of patients pre- and post-SFO administration by 16S rDNA sequencing and bioinformatics analysis. RESULTS: Serum IS and PCS levels were significantly elevated after administration of SFO (IS before 2.52 ± 1.60 mg/dl vs. after 3.13 ± 1.51 mg/dl, P = 0.008; PCS before 2.32 ± 2.44 mg/dl vs. after 3.45 ± 2.11 mg/dl, P = 0.002), while serum IS and PCS levels did not change in the control group. Microbiome analysis in the SFO group showed no significant change in diversity and major components in phylum, class, order, family, gene, and species. CONCLUSION: Administration of SFO increased the serum levels of IS and PCS with no change of major components of gastrointestinal microbiome.

DOI： 10.1007/s10157-020-01892-x

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DOI： 10.1093/NDT/GFAA142|III1769

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Language：Japanese   Publisher：(公社)日本栄養士会  

早朝空腹時呼吸商(RQ)の低下は、夜間飢餓であった状況を示唆する所見である。腎機能の低下に伴い早朝空腹時RQが低下するとの先行研究はあるものの、血液透析(HD)患者においてはその調査は十分ではない。そこでわれわれは、HD患者の早朝空腹時RQとHD後経日経過およびHD実施時間帯の関係を明らかにすることを目的に横断研究を実施した。間接熱量計を用いて、入院HD患者9人[男性3人、女性6人、年齢中央値68(四分位範囲65-68)歳]を対象に、HD実施翌日、2日後、3日後の早朝空腹時RQを測定した。多重比較の結果、3水準間に有意な差を認めた[翌日:0.87(0.85-0.90)、2日後:0.80(0.79-0.84)、3日後:0.82(0.79-0.83)、p<0.05]。しかし、各水準間では有意な差は認めなかった。昼HD(n=4)と夜HD(n=5)の2群に分類した解析では、昼HD群でのみ、3水準間に有意な差を認めた[昼HD群、翌日:0.90(0.87-0.97)、2日後:0.80(0.80-0.85)、3日後:0.81(0.79-0.88)、p<0.05]。本研究は、HD実施時間帯がHD患者の早朝空腹時RQに影響する可能性を示唆した。(著者抄録)

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© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. Background: Parathyroidectomy (PTX) that alleviates clinical manifestations of advanced hyperparathyroidism, including hypercalcemia and hypophosphatemia, is considered the best protection from calcium overload in the kidney. However, little is known about the relationship between postsurgical robust parathyroid hormone (PTH) reduction and perisurgical renal tubular cell viability. Post-PTX kidney function is still a crucial issue for primary hyperparathyroidism (PHPT) and tertiary hyperparathyroidism after kidney transplantation (THPT). Methods: As a clinical study, we examined data from 52 consecutive patients (45 with PHPT, 7 with THPT) who underwent PTX in our center between 2015 and 2017 to identify post-PTX kidney injury. Their clinical data, including urinary liver-type fatty acid-binding protein (L-FABP), a tubular biomarker for acute kidney injury (AKI), were obtained from patient charts. An absolute change in serum creatinine level of 0.3 mg/dL (26.5 μmol/L) on Day 2 after PTX defines AKI. Post-PTX calcium supplement dose adjustment was performed to strictly maintain serum calcium at the lower half of the normal range. To mimic post-PTX-related kidney status, a unique parathyroidectomized rat model was produced as follows: 13-week-old rats underwent thyroparathyroidectomy (TPTX) and/or 5/6 subtotal nephrectomy (NX). Indicated TPTX rats were given continuous infusion of a physiological level of 1-34 PTH using a subcutaneously implanted osmotic minipump. Immunofluorescence analyses were performed by polyclonal antibodies against PTH receptor (PTHR) and a possible key modulator of kidney injury, Klotho. Results: Patients' estimated glomerular filtration rate (eGFR) did not have any clinically relevant change (62.5 ± 22.0 versus 59.4 ± 21.9 mL/min/1.73 m2, NS), whereas serum calcium (2.7 ± 0.18 versus 2.2 ± 0.16 mmol/L, P < 0.0001) and phosphorus levels (0.87 ± 0.19 versus 1.1 ± 0.23 mmol/L, P < 0.0001) were normalized and PTH decreased robustly (181 ± 99.1 versus 23.7 ± 16.8 pg/mL, P < 0.0001) after successful PTX. However, six patients who met postsurgical AKI criteria had lower eGFR and greater L-FABP than those without AKI. Receiver operating characteristics (ROC) analysis revealed eGFR <35 mL/min/1.73 m2 had 83% accuracy. Strikingly, L-FABP >9.8 μg/g creatinine had 100% accuracy in predicting post-PTX-related AKI. Rat kidney PTHR expression was lower in TPTX. PTH infusion (+PTH) restored tubular PTHR expression in rats that underwent TPTX. Rats with TPTX, +PTH and 5/6 NX had decreased PTHR expression compared with those without 5/6 NX. 5/6 NX partially cancelled tubular PTHR upregulation driven by +PTH. Tubular Klotho was modestly expressed in normal rat kidneys, whereas enhanced patchy tubular expression was identified in 5/6 NX rat kidneys. This Klotho and expression and localization pattern was absolutely canceled in TPTX, suggesting that PTH indirectly modulated the Klotho expression pattern. TPTX +PTH recovered tubular Klotho expression and even triggered diffusely abundant Klotho expression. 5/6 NX decreased viable tubular cells and eventually downregulated tubular Klotho expression and localization. Conclusions: Preexisting tubular damage is a potential risk factor for AKI after PTX although, overall patients with hyperparathyroidism are expected to keep favorable kidney function after PTX. Patients with elevated tubular cell biomarker levels may suffer post-PTX kidney impairment even though calcium supplement is meticulously adjusted after PTX. Our unique experimental rat model suggests that blunted tubular PTH/PTHR signaling may damage tubular cell viability and deteriorate kidney function through a Klotho-linked pathway.

DOI： 10.1093/ckj/sfy136

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Polyphosphate (polyP), which is found in various microorganisms and human cells, is an anionic biopolymer consisting of inorganic phosphates linked by high-energy phosphate bonds. Previous studies revealed that polyPs strongly promoted the amyloid formation of several amyloidogenic proteins; however, the mechanism of polyP-induced amyloid formation remains unclear. In the present study using β₂-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, we investigated amyloid formation in the presence of various chain lengths of polyPs at different concentrations under both acidic (pH 2.0 to 2.5) and neutral pH (pH 7.0 to 7.5) conditions. We found that the amyloid formation of β2m at acidic pH was significantly accelerated by the addition of polyPs at an optimal polyP concentration, which decreased with an increase in chain length. The results obtained indicated that electrostatic interactions between positively charged β2m and negatively charged polyPs play a major role in amyloid formation. Under neutral pH conditions, long polyP with 60 to 70 phosphates induced the amyloid formation of β2m at several micromoles per liter, a similar concentration range to that in vivo. Since β2m with an isoelectric point of 6.4 has a slightly negative net charge at pH 7, polyPs were unlikely to interact with β2m electrostatically. PolyPs appear to dehydrate water molecules around β2m under the unfolded conformation, leading to the preferential stabilization of less water-exposed amyloid fibrils. These results not only revealed the pH-dependent mechanism of the amyloid formation of β2m but also suggested that polyPs play an important role in the development of dialysis-related amyloidosis.

DOI： 10.1073/PNAS.1819813116

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Other Link： https://syndication.highwire.org/content/doi/10.1073/pnas.1819813116

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DOI： 10.1186/S41100-019-0205-Z

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A 60-year-old male presented with accelerated hypertension, renal insufficiency, proteinuria, and hematuria. Percutaneous kidney biopsy revealed membranoproliferative glomerulonephritis (MPGN) without any immunoglobulin and complement deposition. On performing electron microscopy, deposits with a tubular, organized structure and approximately 60 nm in diameter were detected in the glomerular subendothelial spaces and mesangial areas. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) demonstrated the significantly increased deposition of fibrinogen and fibronectin in glomeruli. Immunohistochemistry and immunoelectron microscopy demonstrated that the deposits were composed of fibrinogen. Here we report a case of cryofibrinogen -associated GN in which LC-MS/MS and immunoelectron microscopy were useful for diagnosis. When MPGN with organized deposits without the deposition of immunoglobulins and complements is diagnosed, we considered the cryofibrinogen-associated GN in one of the differential diagnosis, and even skin symptoms cannot be detected.

DOI： 10.1016/j.ehpc.2018.12.002

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DOI： 10.1016/J.EHPC.2019.01.001

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

Senescent cells have deleterious effects on the tissue microenvironment through proinflammatory senescence-associated secretory phenotypes; meanwhile, the onset of glomerulonephritis is predominant in younger adults. To clarify the influence of aging on the onset and development of glomerulonephritis, we used a murine model of antibody-mediated nephritis. Sheep nephrotoxic serum was administered in C57BL/6J mice at 12 weeks (adult) or 18 months old (aged) after pre-immunization with sheep IgG. Depositions of sheep IgG and autologous mouse IgG along the glomerular basement membrane and the serum titer of anti-sheep IgG-specific mouse IgG were similar between adult and aged mice. However, kidney injury was depressed in aged mice, accompanied by reduced macrophage infiltration in the glomeruli. The mRNA expression of most chemokines involved in monocyte/macrophage chemotaxis was not different between adult and aged mice, but the cell surface expression of C-C chemokine receptor (CCR) 1 and CCR2 was down-regulated in the monocyte/macrophage lineage cells infiltrating the kidneys of aged nephritic mice. Furthermore, expression of all four isotypes of the Fc gamma receptor (Fc gamma R) was reduced in these cells. Both CCR and Fc gamma R expression were down-regulated in monocyte/macrophage lineage cells, resulting in attenuated glomerular infiltration of these cells and impaired glomerular injury in aged mice.

DOI： 10.1093/gerona/gly019

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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© 2017 Asian Pacific Society of Nephrology Aim: Dialysis-related amyloidosis (DRA) exhibits multiple bone-articular lesions, such as carpal tunnel syndrome (CTS), trigger finger (TF), spinal canal stenosis (SCS), destructive spondyloarthropathy (DSA), bone cysts, and joint pains. DRA leads to a decrease in activities of daily living (ADL). We investigated the initiation of CTS and TF, and evaluated the relationship between walking disturbances and bone-articular lesions or joint pains. Methods: A multicentre cross-sectional study was performed. Eighty-two patients with clinical DRA from 20 hospitals in Japan were evaluated. Results: Of the 82 patients, the first symptom of DRA was CTS in 39 patients (47.6%) and TF in 21 (25.6%). The mean new-onset vintages of 21 earlier cases in the CTS and TF groups were 86.1 ± 36.3 and 133.2 ± 56.4 (mean ± SD) months, respectively (P = 0.0091). The development of SCS and DSA appeared to be later than CTS and TF. Multiple regression analysis revealed that knee joint pain was a significant contributor to walking disturbances. Conclusion: Carpal tunnel syndrome appeared significantly earlier than TF since the initiation of dialysis. In the advanced phase, knee joint pain was a major cause of decreased ADL in patients with clinical DRA.

DOI： 10.1111/nep.13077

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Language：Japanese   Publisher：(公社)日本臨床工学技士会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Visceral disseminated varicella zoster viral (VZV) infection is a rare but severe complication with a high mortality rate in immunosuppressed individuals, and an increased susceptibility to VZV has been reported in kidney transplant recipients who are treated with mycophenolate mofetil (MMF). In Japan, MMF is currently approved for patients with lupus nephritis (LN) and data to indicate its optimal dosage are still insufficient. Case presentation: A 46-year-old Japanese woman with rheumatoid arthritis was diagnosed as having systemic lupus erythematosus (SLE) and LN class III (A/C). Although initial remission-induction therapy with prednisolone and tacrolimus was started, her serum creatinine level and urinary protein excretion were elevated. Methylprednisolone pulse therapy was added, and tacrolimus was switched to MMF. Two months after admission when she was taking 40 mg of PSL and 1500 mg of MMF daily, she suddenly developed upper abdominal pain and multiple skin blisters, and disseminated visceral VZV infection was diagnosed. Laboratory examinations demonstrated rapid exacerbation of severe acute liver failure and coagulation abnormalities despite immediate multidisciplinary treatment, and she died of hemorrhagic shock 7 days after the onset of abdominal pain. A serum sample collected at the time of admission revealed that she had recursive VZV infection. Conclusions: MMF together with high-dose glucocorticoid therapy may increase the risk of VZV infection in Asian patients with SLE. Accumulation of evidence for parameters of safety, such as the area under the blood concentration-time curve of mycophenolic acid, should be urgently considered in order to establish a safer protocol for remission induction therapy in Asian patients with LN.

DOI： 10.1186/s13104-018-3271-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Background: It is well known that atrophic renal changes are associated with chronic kidney disease (CKD) progression, but conventional diagnostic imaging methods such as noncontrast-enhanced computed tomography and magnetic resonance imaging (MRI) have been insufficient for precisely assessing kidney function because they cannot clearly distinguish between the medulla and cortex. Hence, here we used noncontrast-enhanced steady-state free precession (SSFP) MRI with a spatially selective inversion recovery (IR) pulse to improve visibility for renal corticomedullary differentiation and evaluated the association between morphological parameters and kidney function in patients with CKD. Methods: Kidney corticomedullary contrast ratio, cortical and medullary areas, and minimal cortical thickness of 107 patients with CKD G1–G5 were measured using SSFP MRI with a spatially selective IR pulse and the association between these morphological parameters and kidney function were evaluated. Results: Corticomedullary contrast ratio was significantly improved on SSFP MRI compared with conventional in-phase T1-weighted gradient-echo MRI and positively correlated with estimated glomerular filtration ratio (eGFR), raw eGFR, and 24-h creatinine clearance. The medullary and cortical areas and minimal cortical thickness also positively correlated with those of kidney functional markers and the age. In patients with CKD and diabetes mellitus (DM), the correlation coefficients between raw eGFR and morphological parameters were higher than those in patients without DM, while minimal cortical thickness was larger in CKD patients with DM with a raw eGFR ≥ 45 mL/min. Conclusion: Kidney morphological parameters measured with SSFP MRI were clearly correlated with kidney function in patients with CKD, including those with advanced kidney dysfunction.

DOI： 10.1007/s10157-017-1413-x

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DOI： 10.1186/S41100-018-0161-Z

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Language：Japanese   Publisher：(公社)日本透析医会  

背景・目的:蛋白結合尿毒症物質(protein-bound uremic toxins;PBUTs)の血中濃度高値は種々の透析関連合併症の原因となる。我々はヘキサデキル基固定セルロースビーズ(hexadecyl-immobilized cellulose bead;HICB)のPBUTsの吸着効果について臨床的に検討した。方法:HICBを含有したカラム(リクセルS-35)を維持血液透析患者に使用した。カラム通過前後と2週間使用前後の血清インドキシル硫酸(indoxyl sulfate;IS)、インドール酢酸(indole acetic acid;IAA)、フェニル硫酸(phenyl sulfate;PhS)、そしてpクレシル硫酸(p-cresyl sulfate;PCS)濃度を質量分析により測定した。結果:リクセルS-35通過後に蛋白結合していない血中フリーIS、IAA、PhSとPCS濃度は34.4±30.0%、34.8±25.4%、28.4±18.0%と34.9±22.1%減少した。しかし、蛋白結合したPBUTsはカラム通過後に有意に減少しなかった。リクセルを2週間使用したが、血中PBUT値は有意に低下しなかった。結論:HICBsはPBUTsを部分的に吸着した。この吸着効果は臨床的に十分でなく、今後PBUTs吸着効果のより優れた血液浄化器の開発が望まれる。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

Background: In patients with normophosphatemia with chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) increase urinary phosphate excretion while maintaining serum phosphate within the normal range. Recent reports have shown that, in this stage, phosphate binders do not decrease serum FGF23 and PTH levels. Iron deficiency promotes transcription of FGF23 and iron-supplementation for iron deficiency decreases serum FGF23 levels. We hypothesized that ferric citrate hydrate, an iron-based phosphate binder, will decrease serum FGF23 levels in patients with non-dialysis-dependent CKD with normophosphatemia and iron deficiency. Methods: This was a single-center, randomized, open-label interventional study. The inclusion criteria were as follows: (1) eGFR &lt
45 mL/min/1.73 m2, (2) normophosphatemia, (3) iron deficiency. Patients were assigned to the following groups: ferric citrate hydrate (FCH)-group, sodium ferrous citrate (SFC)-group, and control-group. After 12 weeks of intervention, we evaluated serum FGF23 levels and CKD-mineral bone disorder markers. Results: There were 17 patients in the FCH-group, 14 in the SFC-group, and 9 in the control-group. The serum ferritin levels increased in the FCH-group and SFC-group compared with baseline. Serum FGF23 levels were unchanged
the change in the FCH-group was from 52.91 RU/mL (42.48–72.91) to 40.00 RU/mL (30.30–58.13) (P = 0.1764). However, in the FCH-group, serum PTH levels significantly decreased compared with baseline, from 68.00 pg/mL (49.00–141.00) to 60.00 pg/mL (44.00–144.00) (P = 0.0101). Conclusion: Iron-based phosphate binder did not decrease serum FGF23 levels, but decreased serum PTH levels.

DOI： 10.1007/s10157-017-1510-x

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Language：Japanese   Publisher：新潟急性血液浄化研究会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Ltd  

Earlobe creases are surrogate markers for high risk of cardiovascular disease. There is no data concerning earlobe creases among hemodialysis patients, who have an increased risk of cardiovascular disease. A cross-sectional study was conducted to determine the prevalence of earlobe creases and their association with prevalent cardiovascular disease among hemodialysis patients. Patients undergoing hemodialysis were recruited from five outpatient hemodialysis centers. Both earlobes were photographed during a dialysis session with the patient in a supine position and the photos evaluated independently by two experienced nephrologists blinded to the participants' clinical characteristics. Prevalent cardiovascular diseases were defined as a history of myocardial infarction, cerebrovascular accident, or peripheral vascular disease. Sensitivity, specificity, and positive and negative predictive values for detection of prevalent cardiovascular disease were calculated. Logistic analysis was used to examine the association between earlobe creases and prevalent cardiovascular disease. Earlobe creases were identified in 24.5% of 330 hemodialysis patients (200 men
mean age, 67.8 years). The prevalence of earlobe creases increased with age for men (P for trend &lt
0.0001), but not for women (P for trend = 0.07). Sensitivity, specificity, and positive and negative predictive values were 30.9% (95% confidence interval, 21.9–41.6), 77.5% (71.9–82.3), 30.9% (21.9–41.6), and 77.5% (71.9–82.3), respectively. Multivariate logistic analyses indicated the prevalence of earlobe crease was not associated with prevalent cardiovascular diseases. The prevalence is similar to that previously reported for Japanese individuals not undergoing dialysis. No association between earlobe creases and prevalent cardiovascular diseases was identified.

DOI： 10.1111/1744-9987.12567

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NEPHROLOGY  

Background and objectives Prior studies have shown that sevelamer attenuates progression of arterial calcification and may reduce the risk of death compared with calcium-based phosphate binders. In clinical practice, however, sevelamer is used not only as an alternative but also as an add-on therapy in patients already being treated with calcium-based phosphate binders. We analyzed the Dialysis Outcomes and Practice Patterns Study (DOPPS) data to test the hypothesis that the initiation of sevelamer is associated with improved survival in patients on hemodialysis treated with calcium-based phosphate binders.
Design, setting, participants, & measurements We included 12,564 patients from DOPPS phase 3 and phase 4 (2005-2011) who were prescribed calcium-based phosphate binders at baseline or before sevelamer treatment. Mortality risk was assessed using a sequential stratification method to identify as-yet-untreated patients who were appropriately matched to the newly treated patients on the basis of their risk of death.
Results Of 12,564 patients, 2606 were subsequently treated with sevelamer hydrochloride or sevelamer carbonate. After beginning sevelamer therapy, mean serum phosphorus levels decreased by 0.3 mg/dl in the first 4 months and gradually decreased thereafter. We matched 2501 treated patients with at least one as-yet-untreated patient. Patients treated with sevelamer had a 14% lower risk for mortality compared with as-yet-untreated patients (hazard ratio, 0.86; 95% confidence interval, 0.76 to 0.97). Similar results were observed in the sensitivity analyses when changing the matching calipers or the treated and as-yet-untreated ratios, and by using propensity score matching.
Conclusions The use of sevelamer as an add-on or alternative therapy to calcium-based phosphate binders is associated with improved survival in patients on maintenance hemodialysis.

DOI： 10.2215/CJN.13091216

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Introduction: Late referral to a nephrologist, the type of vascular access, nutritional status, and the estimated glomerular filtration rate (eGFR) at the start of hemodialysis (HD) have been reported as independent risk factors of survival for patients who begin HD. The aim of this study was to clarify the influence of the HD-free interval from the time of an eGFR of 10 ml/min per 1.73 m2 (IGFR10-HD) on patient outcome. Methods: We enrolled 124 patients aged older than 20 years who had HD initiated in a general hospital. The predictive factor was the HD-free IGFR10-HD. The primary outcome was the relationship of the HD-free interval on death or the onset of a cardiovascular event. Survival analysis was performed using the Cox regression model. Results: The median IGFR10-HD was 159 days (range: 2-1687 days). The median eGFR at the initiation of HD was 5.48 ml/min per 1.73 m2. Sixty-seven of 124 patients (54.0%) reached the primary outcome. Of these, 29 died and 38 experienced a cardiovascular event. In univariate analysis, older age, a history of cardiovascular disease, nephrologic care for <6 months, higher modified Charlson comorbidity index score, poor performance status, temporary catheter, edema, diabetic retinopathy, and nonuse of erythropoiesis-stimulating agent were statistically related to the primary outcome. The unadjusted hazard ratio per log-transformed IGFR10-HD was 0.393 (95% confidence interval [CI]; 0.244-0.635; P < 0.001) and the hazard ratio adjusted for confounding factors was 0.507 (95% CI: 0.267-0.956; P = 0.036). Discussion: A longer HD-free IGFR10-HD was associated with a lower risk of death or a cardiovascular event. The interval could be considered an independent prognostic factor for outcomes in patients on HD.

DOI： 10.1016/j.ekir.2017.01.015

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS  

Prolactin is a polypeptide hormone with over 300 separate biologic activities. Its serum level is increased during pregnancy and lactation, and it has been reported that pregnancy and lactation affect drug and steroid metabolism in mice and humans. Several studies reported that pregnancy or lactation influences liver cytochrome P450 (P450) expression and its activity, affecting the biosynthesis of steroids and xenobiotics through growth hormone or sex hormones; however, the role of prolactin as the regulator of liver P450 expression has not been elucidated so far. In the present study, we focused on prolactin as the regulator of expression of liver sex-predominant genes, including P450s. To investigate the role of prolactin in the hepatic gene expressions, pCAGGS expression vector containing mouse prolactin cDNA was transfected by hydrodynamic injection into both male and female mice. Hyperprolactinemia phosphorylated signal transducer and activator of transcription 5 in the liver and augmented female mouse liver mRNA expression of Cyp3a16, Cyp3a41, Cyp3a44, Cyp2b9, and prolactin receptor genes, whose expressions were female-predominant in hepatocytes. Moreover, liver expression of male-predominant genes such as Cyp2d9, Cyp7b1, Mup1, and Alas2 were reduced in male mice with hyper-prolactinemia. The serum levels of conventional regulators of hepatic gene expressions, growth hormone, and testosterone were not affected by hyperprolactinemia. We demonstrated that prolactin upregulated female-predominant genes in female mice and downregulated male-predominant genes in male mice. We conjecture that higher concentration of prolactin would alter steroid and xenobiotic metabolisms by modulating hepatic P450 gene expressions during pregnancy and lactation.

DOI： 10.1124/dmd.116.074658

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

IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20-40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established.
We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22).
There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 +/- 4.4 vs. 9.9 +/- 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02).
In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

DOI： 10.1007/s10157-016-1282-8

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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DOI： 10.1016/J.IJCME.2016.08.002

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Authorship：Lead author,　Corresponding author  

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The Oxford classification of IgA nephropathy consists of four markers as prognosticators. We retrospectively examined the relevance of extracapillary proliferation involving cellular and fibrocellular crescents (Ex) and arteriolar hyalinosis (A) on the long-term outcome of renal function.
A total of 314 Japanese patients who were diagnosed with IgA nephropathy, with 12 months or more of follow-up period were included in this study. A total of 186 patients were with UP aeyen 0.5 g/day. Patients with diabetes mellitus or severe kidney injury (eGFR &lt; 30 ml/min/1.73 m(2)) were excluded. The presence of Ex and A were scored 0 in the absence, and 1 in the presence, of each lesion. The end point was determined as a 50 % reduction in initial eGFR or end-stage renal disease defined as eGFR &lt; 15 ml/min/1.73 m(2).
In univariate analyses, the kidney survival rate was significantly lower in patients with Ex1 and A1 if UP aeyen 0.5 g/day. In the patients with UP &lt; 0.5/day, none of the clinical and pathological parameters was determined as a risk factor. In the multivariate model including pathological parameters, Ex1 and A1 were independent risk factors for renal outcome if UP aeyen 0.5 g/day. In those patients treated with RAS-blocker or treated before introduction of methylprednisolone pulse therapy, Ex was the only independent risk factor. In multivariate analysis including clinical parameters, eGFR alone was a risk factor, due to strong correlation with other parameters.
Ex and A would be associated with the renal outcome of the patients with UP aeyen 0.5 g/day.

DOI： 10.1007/s10157-015-1185-0

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Leptin and IL-23 production in NTS nephritis.Leptin, one of the typical adipokines, is reported to promote T(h)17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob (FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative real-time PCR (qRT-PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT-PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/ob mice 7 days after NTS injection. The T(h)17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/ob mice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and T(h)17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.

DOI： 10.1093/intimm/dxv067

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer Japan  

There have been several lines of evidences for familial aggregation of IgA nephropathy (IgAN), as well as mesangial deposition of IgA, suggesting that the susceptibility to this disease is genetically controlled. In our institute, family histories of hematuria, end-stage kidney disease, and glomerulonephritis are observed in about 10 % of cases with IgAN, even in those without any significant hereditary nephritis or kidney diseases. Recent large-scale genome-wide association studies (GWAS) of sporadic IgAN have identified multiple susceptibility loci, providing an insight into the genetic architecture of this disease, although each of their individual impact to the development of the disease is still not enough. It has been recognized that most of these loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. Further elucidation of the role of genetic variants underlying IgAN, and hologenetic views of gene variants and environmental factors, would be necessary to understand the precise pathogenic mechanism of IgAN in more detail.

DOI： 10.1007/978-4-431-55588-9_3

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DOI： 10.1186/S41100-016-0056-9

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The parathyroid gland secretes 1-84 and 7-84 parathyroid hormone (PTH) fragments, and its regulation is dependent on stimulation of the extracellular calcium-sensing receptor. While the intact PTH system detects both PTH fragments, the whole PTH system detects the 1-84PTH but not the 7-84PTH. Cinacalcet hydrochloride (CH) binds to calcium-sensing receptor as a calcimimetic. Here we investigated the role of CH treatment in the assessment of parathyroid gland function.
Stable adult dialysis patients for whom CH therapy was planned were included. Patients for whom CH therapy was not planned were simultaneously included as the control group.
The CH group (n = 44) showed significantly higher circulating levels of Ca, intact PTH, and whole PTH, before the CH treatment than the control group (n = 112). The Ca, intact PTH, and whole PTH levels decreased along with the CH therapy, and the Ca levels became comparable in the 8th week of treatment and thereafter. The CH group in the 8th week and thereafter showed significantly lower whole/intact PTH ratios than the control group, while the whole/intact PTH ratio was not significantly different between before and during the CH therapy. A multiple regression analysis revealed that the whole/intact PTH ratio was almost constant, but both the serum Ca level and a CH therapy could potentially modify the fixed number. When the whole PTH levels were estimated by intact PTH levels using the relationship between them in the control group, the levels were clearly overestimated in the CH group.
Although the direct effect of CH on the whole/intact PTH ratio is masked by its hypocalcemic action, we could successfully demonstrate that the ratio in CH users is lower than that in the non-users with comparable levels of serum Ca. Evaluating parathyroid function with intact PTH according to the clinical practice guidelines in patients being treated with CH may lead to significant overestimation and subsequent overtreatment.

DOI： 10.1007/s10157-014-1045-3

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 53-year-old man with an asymptomatic anterior mediastinal tumor undergoing hemodialysis was referred to our institution. He was diagnosed with thymic basaloid carcinoma based on the findings of a chest tomography-guided biopsy and successfully treated with carboplatin (300 mg/m(2)/day) and paclitaxel (200 mg/ m2/day) on day 1 for six three-week cycles. To our knowledge, this is the first report regarding the efficiency of a carboplatin dose-definition method based on the body surface area with paclitaxel in a hemodialysis patient. This report may therefore be useful for treating hemodialysis patients who are candidates for carboplatin and paclitaxel therapy.

DOI： 10.2169/internalmedicine.54.3484

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

Background/Aim: Dietary phosphate intake and vitamin D receptor activator (VDRA) regulate fibroblast growth factor 23 (FGF23); iron may modulate FGF23 metabolism. We aimed to determine whether oral iron supplementation influences serum FGF23 concentration in hemodialysis (HD) patients, while excluding the effect of dietary phosphate intake. Methods: This prospective study enrolled 27 maintenance HD patients with iron deficiency and hyperphosphatemia treated with sevelamer-HCl. The phosphate binder was changed from sevelamer-HCl to ferric citrate hydrate (FCH) to maintain constant phosphate levels. VDRA, other phosphate binders, and cinacalcet HCl were not changed. Serum intact FGF23, C-terminal FGF23 (C-term FGF23), intact parathyroid hormone (PTH), 1,25(OH) 2 D and other parameters were monitored for 12 weeks. Results: Serum phosphate levels (5.89 +/- 1.45 mg/dl at baseline, 5.54 +/- 1.35 mg/dl at 12 weeks) and 1,25(OH) 2 D levels were unchanged. Serum ferritin levels increased from 25.6 +/- 24.3 ng/ml at baseline to 55.8 +/- 33.5 ng/ml at 12 weeks with FCH administration. Serum intact FGF23 and C-term FGF23 levels significantly decreased at 12 weeks compared with baseline (2,000 (1,300.0-3,471.4) to 1,771.4 (1,142.9-2,342.9) pg/ml, p = 0.01, and 1,608.7 (634.8-2,308.7) to 1,165.2 (626.1-1,547.8) RU/ml, p = 0.007, respectively); serum intact PTH levels significantly increased (96 (65-125) to 173 (114-283) pg/ml, p &lt; 0.001). Conclusions: Oral FCH administration decreased serum intact FGF23 and C-term FGF23 levels and increased intact PTH levels; phosphate and 1,25(OH)(2)D levels were unchanged. Oral FCH administration to treat iron deficiency is a possible strategy for reducing serum FGF23 levels independent of phosphate and VDRA. (C) 2015 The Author(s) Published by S. Karger AG, Basel

DOI： 10.1159/000440968

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Language：Japanese   Publisher：The Japanese Society for Dialysis Therapy  

DOI： 10.4009/jsdt.48.393

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Other Link： http://search.jamas.or.jp/link/ui/2015372426

Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：English   Publisher：NATURE PUBLISHING GROUP  

DOI： 10.1038/ki.2013.412

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Despite significant therapeutic advances, mortality of dialysis patients remains unacceptably high. The aim of this study is to compare mortality and its causes in dialysis patients with those in the general Japanese population. We used data for 2008 and 2009 from the Japanese Society for Dialysis Therapy registry and a national Vital Statistics survey. Cardiovascular mortality was defined as death attributed to heart failure, cerebrovascular disorders, myocardial infarction, hyperkalemia/sudden death, and pulmonary thromboembolism. Non-cardiovascular mortality was defined as death attributed to infection, malignancies, cachexia/uremia, chronic hepatitis/cirrhosis, ileus, bleeding, suicide/refusal of treatment, and miscellaneous. We calculated standardized mortality ratios and age-adjusted mortality differences between dialysis patients and the general population for all-cause, cardiovascular versus non-cardiovascular, and cause-specific mortality. During the 2-year study period, there were 2284272 and 51432 deaths out of 126 million people and 273237 dialysis patients, respectively. The standardized mortality ratio for all-cause mortality was 4.6 (95% confidence interval, 4.6-4.7) for the dialysis patients compared to the general population. Age-adjusted mortality differences for cardiovascular and non-cardiovascular disease were 33.1 and 30.0 per 1000 person-years, respectively. The standardized mortality rate ratios were significant for all cause-specific mortality rates except accidental death. Our study revealed that excess mortality in dialysis patients compared to the general population in Japan is large, and differs according to age and cause of death. Cause-specific mortality studies should be planned to improve life expectancies of dialysis patients. © 2012 The Authors Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.

DOI： 10.1111/j.1744-9987.2012.01144.x

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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A combination of healthy lifestyle factors is associated with lower risks of coronary heart disease, diabetes and stroke, but little is known about its association with chronic kidney disease (CKD). This study analyzed the effect of a combination of healthy lifestyle factors on the incidence of proteinuria among participants without CKD. Of the 7565 persons aged 40-79 years who participated in the Specific Health Checkups and Guidance System in Sado Island, Japan in 2008, 4902 participants (2015 males) without CKD were included. The healthy lifestyle score was calculated by summing the total number of lifestyle factors for which the participants were at low risk. Low risk was defined as (1) nonsmoker, (2) body mass index (BMI) &lt
25 kg m -2, (3) moderate or less alcohol consumption, (4) regular exercise and (5) better eating patterns. Logistic analysis was used to examine the relationship between the baseline score in 2008 and the development of proteinuria in 2009. Proteinuria developed in 2.2% of participants (males, 3.2
females, 1.5%). Compared with participants with a healthy lifestyle score of 0 to 2, participants with a score of 5 had a lower risk (odds ratio: 0.39, 95% confidence interval: 0.16-0.94), independently of having diabetes, hypertension and hypercholesterolemia. Overall, 47% of the cases in this cohort could be attributed to lack of adherence to this low-risk pattern. These findings underscore the importance of a healthier lifestyle in preventing CKD. © 2013 The Japanese Society of Hypertension All rights reserved.

DOI： 10.1038/hr.2012.186

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Infectious disease is the second leading cause of death among dialysis patients, and it is generally assumed that the mortality rate of infectious disease is considerably higher in dialysis patients than in the general population. There are no comprehensive studies on this issue and on the contribution of each category of infectious disease to excess mortality in dialysis patients in Japan. We used mortality data reported to the Japanese Society for Dialysis Therapy and national Vital Statistics data for 2008 and 2009. We calculated standardized mortality ratios and compared the mortality rates for each category of infectious disease. During the 2-year study period, 274 683 and 10 435 deaths from infectious diseases were recorded in 126 million people and 273 237 dialysis patients, respectively. The standardized mortality ratio for all infectious diseases was 7.5 (95% confidence interval, 7.37.6) in dialysis patients with respect to the general population in Japan. The categories of infectious disease with a significantly higher standardized mortality ratio among the dialysis patients were sepsis, peritonitis, influenza, tuberculosis, and pneumonia and in that order. In particular, the mortality rate of sepsis contributed to 69.5% of the difference in infectious disease mortality between dialysis patients and the general population. This study underlines markedly increased mortality from infectious diseases, particularly from sepsis, in dialysis patients compared with the general population.

DOI： 10.1111/j.1744-9987.2012.01062.x

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Hypogammaglobulinemia is a reduction or absence of immunoglobulin, which may be congenital or associated with immunosuppressive therapy. In addition to infectious diseases, autoimmune diseases have also been reported in patients with hypogammaglobulinemia. A 26-year-old man with hypogammaglobulinemia had multiple joint pain and swelling with erosive changes in the proximal interphalangeal joint of the right middle finger on X-ray film, mimicking rheumatoid arthritis (RA). As polyarthritis remained after immunoglobulin replacement therapy and there was no finding indicating any infection at that time, a diagnosis of RA was made. Prednisolone and etanercept were started. However, his polyarthritis did not improve and he developed meningitis and massive brain ischemia. Finally, a diagnosis of disseminated Mycoplasma hominis infection was made. The differential diagnosis of polyarthritis in patients with hypogammaglobulinemia should strictly exclude Mycoplasma infection by culture with special media or longer anaerobic culture, and molecular methods for mycoplasma.

DOI： 10.2169/internalmedicine.51.6058

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The morphological appearance of an osteoblast largely alters with its differentiation and maturation, along with the change of cell function. We quantitatively observed the osteoblast morphology and compared it with bone metabolism. Biopsied iliac bone samples obtained from 77 dialysis patients (14 mild change, 37 osteitis fibrosa, 2 osteomalacia, 8 mixed, and 16 adynamic bone) were included in the study. Osteoblast appearances were classified into three groups: (i) type II and III osteoblasts, namely, active osteoblasts characterized by cuboidal or columnar shapes with or without a nuclear clear zone; (ii) type IV osteoblasts, lining osteoblasts characterized by extremely thin cytoplasm; and (iii) type V osteoblasts, apoptotic osteoblasts characterized by nuclear chromatin concentration. The results were quantitatively expressed as the length of bone surface covered by each type of osteoblasts. The type II and III osteoblasts were predominant in osteitis fibrosa, mixed, and mild change. The type IV osteoblasts were overwhelmingly predominant in adynamic bone. The type V osteoblasts appeared most frequently in osteitis fibrosa, followed by mixed and mild change. Both absolute and relative lengths of bone surface covered by the type V osteoblasts were significantly higher in the high-turnover bone group (osteitis fibrosa and mixed) than the low-turnover bone group (adynamic bone and osteomalacia). The type V osteoblasts were slightly correlated with serum intact parathyroid hormone levels. In conclusion, a high bone-turnover condition seems to be associated with the promotion of osteoblastic apoptosis in dialysis patients. This finding may explain the fact that osteopenia develops faster in CKD patients with high turnover of bone.

DOI： 10.1111/j.1744-9987.2011.00919.x

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Background and objectives: A new assessment system for bone histology, termed the turnover-mineralization-volume system, is advocated for patients with chronic kidney disease-related mineral and bone disorder. The system measures cancellous bone volume (BV/TV) as a third major evaluation axis; however, the physiologic significance of BV/TV remains unclear.
Design, setting, participants, & measurements: Conventional bone histomorphometry was performed in 75 iliac bone samples obtained from dialysis patients. In 47 of the 75 samples, the remaining samples were subjected to direct microfocus x-ray computed tomographic observation. Quantitative morphologic examinations, including micro-bone mineral densitometry, and marrow space star volume, Euler number, and node-strut analyses, were performed in the virtual three-dimensional space reconstructed from the microfocus x-ray computed tomographic images.
Results: The levels of BV/TV were comparable in each of the conventional bone histomorphometric criteria. No significant correlations were found between BV/TV and other parameters. Two- and three-dimensional BV/TVs were significantly correlated with cancellous bone mass but not with cortical bone thickness or cortical bone mass. Two- and three-dimensional BV/TVs were significantly correlated with trabecular bone connectivity as determined by marrow space star volume, Euler number, and node-strut analyses.
Conclusions: In dialysis patients, BV/TV is not dependent on bone turnover or bone mineralization. BV/TV is unlikely to indicate the balance between bone formation and bone resorption. Instead, it reflects trabecular bone connectivity, and improved trabecular bone connectivity is physiologically beneficial in terms of bone quality. The turnover-mineralization-volume system offers an advantage over the conventional system for the assessment of bone quality. Clin J Ant Soc Nephrol 5: 292-298, 2010. doi: 10.2215/CJN.04150609

DOI： 10.2215/CJN.04150609

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Assessment of cancellous bone connectivity has the potential to aid in predicting fracture risk. Today, cancellous bone connectivity is generally assessed using bone sections obtained from biopsy. However, how reliably such two-dimensional (2-D) analyses visualize the 3-D properties has not been evaluated. Biopsied iliac bone samples were obtained from 47 chronic hemodialysis patients. Bone samples were observed using a microfocus X-ray computed tomography (mu CT) system en bloc, and the cancellous bone microstructure was quantitatively assessed at both the 2- and 3-D levels. Cancellous bone microarchitecture was successfully reconstructed from the data obtained by the mu CT system. Most of the results from node-strut analysis (NSA) revealed no statistically significant correlations between the 2- and 3-D analyses, with the exception that the number of nodes (N.Nd/TV) showed a mild but significant correlation. In contrast, the marrow space star volumes (V*m) of the 2- and 3-D analyses were highly correlated. NSA parameters including N.Nd/TV showed significant correlations with V*m at the 3-D level. In conclusion, V*m values were similar in the 2- and 3-D analyses, while most of the 2-D NSA parameters did not reflect the 3-D ones. Since V*m and most of the NSA parameters were correlated in the 3-D analyses, 2-D NSA would seem to have serious limitations for the assessment of cancellous bone microstructural properties. Further studies will thus be needed to establish appropriate methods for assessing cancellous bone connectivity in clinical practice.

DOI： 10.1007/s00223-008-9194-6

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

Background: It is unclear whether the prevalence of gallbladder stones (GBS) is higher in patients with chronic kidney disease (CKD). Methods: A total of 398 patients with CKD of each of the 5 disease stages [CKD1:26; CKD2:52; CKD3:58; CKD4:48; CKD5:214, of whom 61 were predialysis and 153 were on dialysis (CKD5D)] were included in this study. Those in whom GBS were detected by ultrasonographic examination or who had a history of cholecystectomy owing to GBS were considered GBS patients. Results: In comparison to the GBS prevalence of 5.9% in the control group, that in CKD patients increased with the advancement of the disease stage (CKD1: 7.7%; CKD2: 15.4%; CKD3: 19.0%; CKD4: 20.8%; CKD5 predialysis: 21.3%; CKD5D: 22.9%). The prevalence was significantly greater in CKD5 patients than in the control group. CKD5 is a risk factor for GBS independent of age or sex. However, no significant relationship was found between the prevalence of GBS and the duration of hemodialysis therapy in CKD5D patients. Age was the only factor that was associated with GBS in predialysis CKD patients. Conclusion: The risk of GBS formation was high in predialysis CKD patients. Although the risk disappeared in CKD5D patients, the prevalence of GBS was still significantly higher than in the control population. Factors that promote GBS formation in predialysis CKD patients and/or that inhibit GBS formation in CKD5D patients remain unknown. Copyright (C) 2009 S. Karger AG, Basel

DOI： 10.1159/000199456

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DOI： 10.1159/000199456

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

Calcitriol therapy is a central strategy for the treatment of uremic secondary hyperparathyroidism. Although indiscriminate use of calcitriol may lead to worse outcomes, it is difficult to make a decision to discontinue calcitriol therapy when its parathyroid suppression effect remains unsatisfactory. In this study, intravenous calcitriol was administered to 120 chronic hemodialysis patients. Therapy continued for 48 weeks or until plasma intact parathyroid hormone (iPTH) levels decreased to below 300 pg/ml or until the development of any significant adverse effect. Of the 120 patients, the treatment goal was achieved in 47 patients during the first 4 weeks, in 10 during the next 4 weeks, and in 22 patients thereafter. Logistic regression analysis and stepwise regression analysis revealed that iPTH levels were the only significant predictor of the response to calcitriol therapy at weeks 0 and 4. Besides iPTH, the inorganic phosphate (P) levels were another significant predictor of the ultimate response to calcitriol therapy at week 8. The point of best discrimination for successful treatment was P = 6.0 mg/dl at week 8, or P level at week 8/pretreatment P level = 1.0. In conclusion, the P level at week 8 is a predictor of the response to calcitriol therapy for uremic secondary hyperparathyroidism. Changes in treatment are recommended if patients show unsatisfactory parathyroid suppression with a hyperphosphatemic tendency.

DOI： 10.1007/s00774-007-0809-1

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Authorship：Lead author,　Corresponding author  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastic formation and activity. Circulating OPG levels are elevated in uremia. The role of elevated circulating OPG levels in uremia remains unknown. Blood samples were obtained from 22 non-diabetic dialysis patients who underwent iliac bone biopsy examination. The serum OPG concentration was assayed by ELISA. The circulating OPG levels showed a negative correlation with the ratio of eroded surface/bone surface (ES/BS) in biopsied iliac bone samples among 15 of those with plasma intact PTH levels less than 300 pg/mL (P &lt; 0.05, r(2) = 0.270). Patients with serum OPG levels less than 2.0 ng/mL showed significantly greater ES/BS values than those with levels &gt;= 3.0 ng/mL, while the intact PTH levels were comparable among those groups. These tendencies disappeared when seven patients with plasma intact PTH levels more than 300 pg/mL were included into the analysis. In conclusion, circulating OPG levels showed a significant negative correlation with a bone resorption parameters in dialysis patients with mild secondary hyperparathyroidism. Circulating OPG might have a suppressive effect on osteoclastic bone resorption in dialysis patients.

DOI： 10.1111/j.1744-9987.2006.00375.x

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Language：English   Publisher：SPRINGER TOKYO  

A beta-2M-amyloidosis is a type of systemic amyloidosis that is specifically seen in patients with chronic kidney diseases. The precursor protein of A beta-2M-amyloid fibril is beta 2-microglobulin, and its elevated serum level is the main cause of A beta-2M-amyloidosis in patients with kidney failure. However, the precise mechanism of A beta-2M-amyloidogenesis remains unclear. In vitro analyses of A beta-2M amyloidogenesis are still being actively conducted. Osteolytic lesions are often found around synovial membrane with A beta-2M-amyloid deposition. Both evident osteoclastogenesis and active osteoclastic bone resorption are found, while osteoblastic bone formation is absent in the lesion most likely associated with the inflammation caused by infiltrating macrophages/monocytes into A beta-2M-amyloid deposition. The precise cell biological mechanism of this inflammatory change is unknown. Further studies are needed to establish specific treatments against this as yet unsolved problem with long-term dialysis therapy.

DOI： 10.1007/s00774-005-0669-5

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PubMed

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

Background. The treatment strategy for secondary hyperparathyroidism is generally determined empirically with regards to present parathyroid function and serum calcium (Ca) and inorganic phosphate (Pi) levels. More evidence is needed to avoid the aimless continuation of active vitamin D therapy. Methods. Nondiabetic dialysis patients whose plasma intact parathyroid hormone (iPTH) levels were greater than 300∈pg/ml were included in the study. Maxacalcitol was intravenously injected three times a week. The treatment was continued for 48 weeks, unless the iPTH level was reduced to less than 300∈pg/ml or unfavorable events occurred. The patients whose plasma iPTH levels were below 300∈pg/ml within 48 weeks were defined as those who had been successfully treated. Results. Findings for 146 patients were analyzed, and 96 patients were successfully treated. Serum Pi levels did not significantly increase during the therapy. The pretreatment plasma iPTH levels and serum Ca levels were lower in the patients who were successfully treated with maxacalcitol. A logistic regression study and classifying by stratum analyses revealed that the pretreatment serum Ca levels and plasma iPTH levels were significantly related to the result of maxacalcitol therapy, while the serum Pi levels were not. Analyses using a receiver-operating characteristic curve revealed that the areas under curves obtained for iPTH and Ca were significantly greater than those obtained for Pi (P &lt
0.0001). Conclusions. Serum Ca levels and parathyroid function were correlated with the results of maxacalcitol therapy. Pretreatment serum Pi levels could not predict the result. © Japanese Society of Nephrology 2005.

DOI： 10.1007/s10157-005-0342-2

Scopus

PubMed

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Language：English   Publisher：INFORMA HEALTHCARE  

In beta(2)-microglobulin-related (A beta(2)M) amyloidosis, a serious complication in patients on long-term dialysis, partial unfolding of beta(2)-microglobulin (beta(2)-M) is believed to be prerequisite to its assembly into A beta(2)M amyloid fibrils. Many kinds of amyloid-associated molecules, (e.g., apolipoprotein E (apoE), glycosaminoglycans (GAGs), proteoglycans (PGs)) may contribute to the development of A beta(2)M amyloidosis. In 1990s, the formation of A beta(2)M amyloid fibrils in vitro was first observed at low pH (2.0-3.0). Very recently, low concentrations of 2,2,2-trifluoroethanol (TFE) and the sub-micellar concentration of sodium dodecyl sulfate, a model for anionic phospholipids, have been reported to cause the extension of A beta(2)M amyloid fibrils at a neutral pH, inducing partial unfolding Of beta(2)-m and stabilization of the fibrils. Moreover, apoE, GAGs, and PGs were found to stabilize A beta(2)M amyloid fibrils at a neutral pH, forming a stable complex with the fibrils. Some GAGs, especially heparin, enhanced the fibril extension in the presence of TFE at a neutral pH. Some PGs, especially biglycan also induced the polymerization of acid-denatured beta(2)-M. These findings are consistent with the hypothesis that in vivo, specific molecules that affect the conformation and stability Of beta(2)-m and amyloid fibrils will have significant effects on the deposition of A beta(2)M amyloid fibrils.

DOI： 10.1080/13506120500032352

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING INC  

Background. The predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia.
Methods. Dialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied.
Results. Sixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium x phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 less than or equal to9860 ng/L and iPTH less than or equal to591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 &gt;9860 ng/L and iPTH &gt;591 pg/mL.
Conclusion. Pretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism.

DOI： 10.1111/j.1523-1755.2005.00178.x

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PubMed

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DOI： 10.1159/000081788

PubMed

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

Background/Aim: Today, two kinds of 1-84PTH assays are available in clinical practice. Few studies have directly compared the results of these assays in the same plasma. Methods: Plasma samples were collected from 235 dialysis patients and analyzed by the 1-84PTH-IRMA, intact PTH-IRMA, 1-84PTH-CLIA, and intact PTH-CLIA assays simultaneously. Results: The results obtained by the 1-84PTH-IRMA and 1-84PTH-CLIA were highly correlated to each other (r(2) = 0.971, p &lt; 0.0001). In 90.2-92.3% of patients, the assays agreed when classifying them into three categories based on the K/DOQI guidelines. However, the 1-84PTH assays agreed in only 41.3-83.4% of patients when classifying them into two categories by calculating 1-84PTH/(intact PTH-1-84PTH). Conclusion: The results obtained by the two assays could be regarded as comparable in clinical practice. However, the 1-84PTH/( intact PTH-1-84PTH) ratio has to be carefully applied since it amplified the error of these assays. Copyright (C) 2005 S. Karger AG, Basel.

DOI： 10.1159/000081788

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING INC  

Background. Although several kinds of evidence suggest that glycosaminoglycans (GAGs) and proteoglycans (PGs) may contribute to the development of beta(2) -microglobulin-related (Abeta(2) m) amyloidosis, the precise roles of these molecules for the development of Abeta(2) m amyloidosis are poorly understood.
Methods. We investigated the effects of GAGs and PGs on the depolymerization of Abeta(2) m amyloid fibrils at a neutral pH, as well as on the formation of the fibrils at an acidic pH in vitro, using fluorescence spectroscopy with thioflavin T and electron microscopy.
Results. Depolymerization of Abeta(2) m amyloid fibrils at pH 7.5 at 37degreesC was inhibited dose-dependently by the presence of some GAGs (heparin, dermatan sulfate, or heparan sulfate) or PGs (biglycan, decorin, or keratan sulfate proteoglycan). Electron microscopy revealed that a significant amount of Abeta(2) m amyloid fibrils remained in the reaction mixture with some lateral aggregation. Second, when monomeric beta(2) m was incubated with aggrecan, biglycan, decorin, or heparin at pH 2.5 at 37degreesC for up to 21 days, the thioflavin T fluorescence increased depending on dose and time. Electron microscopy revealed the formation of rigid and straight fibrils similar to Abeta(2) m amyloid fibrils in beta(2) m incubated with biglycan for 21 days.
Conclusion. These results suggest that some GAGs and PGs could enhance the deposition of Abeta(2) m amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of beta(2) m in the fibrils, as well as by acting as a scaffold for the polymerization of beta(2) m into the fibrils.

DOI： 10.1046/j.1523-1755.2003.00167.x

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DUSTRI-VERLAG DR KARL FEISTLE  

Living donor liver transplantation (LDLT) is a treatment for end-stage liver failure, and was developed to overcome the distinct insufficiency of cadaveric donors. Case 1 is a 56-year-old man who had undergone maintenance hemodialysis therapy for 4 years. An LDLT was performed for the treatment of advanced liver cirrhosis and hepatocellular carcinoma. Continuous hemodiafiltration (CHDF) was performed from the 2nd to 5th days after the operation. Case 2 is a 55-year-old man with primary amyloidosis and chronic renal failure. An LDLT was performed for the treatment of severe abdominal distention caused by a large liver volume. Although CHDF was started at the 3rd day after the operation, it was discontinued within 24 hours because of an increased urinary volume. CHDF was required again from the 6th-8th days, after which the blood purification mode was switched to regular intermittent hemodialysis. Meanwhile, no major problems occurred in either case. In conclusion, CHDF was required for about 5 days from the 2nd day after the operation. The application of careful and aggressive blood purification therapy during the perioperative period is a key to successful LDLT in dialysis patients.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

A 39-year-old male with CML who relapsed 5 years and 8 months after allogeneic bone marrow transplantation achieved complete molecular remission following fractionated dose-escalating donor leukocyte infusions. Acute or chronic graft-versus-host host (GVHD) did not occur and the patient remained asymptomatic throughout treatment. Since no prophylaxis against GVHD was administered this case indicated that the graft-versus-leukemia effect is entirely separate from GVHD in certain conditions.

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)東京医学社  

＜文献概要＞はじめに 慢性腎臓病に伴う骨ミネラル代謝異常(chronic kidney disease-mineral and bone disorder:CKD-MBD)アウトカムとして骨折が挙げられている。骨折は慢性腎臓病(chronic kidney disease:CKD)透析患者の日常生活動作(activities of daily living:ADL)・生活の質(quality of life:QOL)を低下させるだけでなく生命予後にも影響する。そのため,骨折リスクと治療の効果を骨代謝マーカーと骨塩量検査で定期的に評価することが重要である。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00714&link_issn=&doc_id=20231005160016&doc_link_id=10.24479%2Fkd.0000000876&url=https%3A%2F%2Fdoi.org%2F10.24479%2Fkd.0000000876&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(株)東京医学社  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00714&link_issn=&doc_id=20230404050018&doc_link_id=%2Faq9jintd%2F2023%2F009403%2F019%2F0424-0429%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faq9jintd%2F2023%2F009403%2F019%2F0424-0429%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本透析医会  

透析用カテーテル(以下カテーテル)は,さまざまな状況で選択できるバスキュラーアクセスとして有用であるものの,カテーテルによる血管壁吸引や血栓形成による脱血不良など機能不全の問題がある.本研究では,これらの機能不全を効果的に改善する制御システムの開発を目的とし,我々が開発したカテーテルの評価システムを用いて評価した.制御システムは血液回路内圧の変化を血液ポンプの制御信号に送り,血液ポンプの回転速度を制御できるようにした.カテーテルの機能不全が発生し回路内が陰圧を呈した場合に,血液ポンプの回転速度を低下させ機能不全の改善を図る.この間に機能不全が改善すれば,血液ポンプは停止せずにもとの回転速度に自動的に戻るが,改善しなければ血液ポンプは停止する.結果として,血液回路内の陰圧が-160mmHg以下に達した時点で血液ポンプの回転速度を低下させた条件では,血液ポンプは停止し機能不全は改善できなかった.しかし,血液回路内の陰圧が-140mmHg以上で血液ポンプの回転速度を低下させた場合は,血液ポンプは停止せずに機能不全を改善することができた.この制御システムによって,機能不全が改善できる可能性が示唆されたので報告する.(著者抄録)

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Language：Japanese   Publisher：(株)アクセス・ケイ  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(有)科学評論社  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：Niigata Blood Purification Conference事務局  

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本理学療法学会連合  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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J-GLOBAL

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Language：Japanese   Publisher：(公社)日本透析医会  

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Language：Japanese   Publisher：(株)メディカ出版  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2020&ichushi_jid=J02946&link_issn=&doc_id=20201112110006&doc_link_id=issn%3D1341-1489%26volume%3D26%26issue%3D12%26spage%3D1118&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D1341-1489%26volume%3D26%26issue%3D12%26spage%3D1118&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

＜文献概要＞透析患者の骨折リスクは一般と比較して極度に大きく,ADL,QOLそして生命予後に影響する.そのため透析患者の転倒・骨折の現状を理解したうえで,その予防法,治療法を実施することが重要である.骨折にはCKD-MBD,骨粗鬆症,透析アミロイドーシスなど骨に直接影響する内因的要因があり,転倒にはサルコペニア,フレイル,あるいはロコモティブシンドロームなど筋力,バランスを損なう要因がある.転倒・骨折リスクは転倒リスク評価やFRAXなど一般的な評価法が応用できると考えるが,一方でCKDあるいは透析固有の因子が大きく影響していると考えられ,対策は多面的かつ総合的な治療が求められる.

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Authorship：Lead author,　Corresponding author  

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Language：Japanese   Publisher：(NPO)日本急性血液浄化学会  

バスキュラーアクセスカテーテル(カテーテル)は、さまざまな問題点を改善するために改良が重ねられている。例えば、カテーテルの抵抗を減少させるために径を太くしたり、血栓形成によるトラブルに対して抗血栓性薬剤をコーティングして改善している。以前、われわれは治療中にカテーテルが血管壁を吸引するトラブルを起こすことに対して、カテーテルを回転することが有効であることを報告した。今回、われわれはカテーテルの構造の違いが対処手技の有効性に影響をあたえるか検討した。対象とするカテーテルは、5種類である。各カテーテルの脱血孔に血管壁を吸引させ、最も改善したのは、脱血孔の開口面が広く立体的な開口面を有しているカテーテルであった。その一方で、最も改善しなかったカテーテルは、脱血孔がシンプルな構造のカテーテルであった。本結果は、カテーテルの構造の違いが血管壁吸引の改善に影響することを示唆する。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J05761&link_issn=&doc_id=20181203380005&doc_link_id=%2Ffe9kyuse%2F2018%2F000902%2F005%2F0111-0115%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffe9kyuse%2F2018%2F000902%2F005%2F0111-0115%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(公社)日本透析医会  

血液透析濾過(hemodiafiltration;HDF)療法は、血液透析では除去されにくい低分子、または中分子尿毒症物質の除去に優れた血液浄化療法である。HDF療法はその濾過した液を補充する方法がいくつかあるが、本邦では近年、ダイアライザーに血液が流入する前に清浄化した透析液を補充する前希釈法によるオンラインHDFの使用が普及している。また治療中の循環動態の維持を目的に、間歇補充型HDFの有用性が報告されている。血液透析かHDFか、HDFであればどの種類を選択するか、それぞれの特徴を理解して治療する必要がある。(著者抄録)

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Language：Japanese  

DOI： 10.20837/42018081093

J-GLOBAL

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

＜文献概要＞ウレミックトキシンは慢性腎臓病(chronic kidney disease: CKD)の進行に伴い血中濃度が増加し,その血中濃度増加と尿毒症症状の発症・進展が関連する分子を総称するものである。ウレミックトキシンの標的臓器は多彩であり,骨もその一つであると考える。インドキシル硫酸,p-クレシル硫酸などの蛋白結合分子,副甲状腺ホルモン(parathyroid hormone: PTH),あるいはレニン-アンギオテンシン-アルドステロン系(renin-angiotensin-aldosterone system: RAAS)などが骨脆弱性に関連する可能性が基礎および臨床研究から明らかにされつつある。中でもウレミックトキシンによる骨のPTHに対する抵抗性・骨質への影響やRAASの骨への影響は大きく骨・ミネラル代謝異常と並び注目するべき病態と考える。

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Language：Japanese  

DOI： 10.19020/CD.0000000568

J-GLOBAL

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Language：Japanese   Publisher：(株)日本メディカルセンター  

＜文献概要＞I 医学的背景 ▼破壊性脊椎関節症は長期透析患者に発症する透析アミロイドーシスの1疾患である.▼頸椎と腰椎を中心にβ2-ミクログロブリン(β2-m)を前駆蛋白質とするアミロイドが沈着することで四肢の神経症状を呈する.II キュア ▼整形外科的保存治療と手術療法が中心となる.▼β2-m吸着カラムや血液透析濾過,β2-mクリアランスのよいダイアライザの使用や清浄化された透析液の使用が,β2-mを低値に保つことに有効である.III ケア ▼手根管症候群など他の透析アミロイドーシスを早期に診断,治療することが破壊性脊椎関節症の進展抑制に有効である.

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

DOI： 10.19020/CD.0000000349

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Language：Japanese   Publisher：(公財)鈴木謙三記念医科学応用研究財団  

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Language：Japanese  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：Japanese  

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Language：Japanese   Publisher：新潟急性血液浄化研究会  

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Language：Japanese   Publisher：(株)日本医事新報社  

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Language：Japanese  

DOI： 10.19020/KB.0000000070

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

副甲状腺ホルモン(parathyroid hormone;PTH)は血中で全長の1-84 PTHほか,大小のフラグメントとして存在している.CKD患者ではリンの蓄積,低カルシウム血症,活性型ビタミンDの減少などにより,代償的にPTHが分泌されるが高度となると二次性副甲状腺機能亢進症を発症する.PTHはCKD患者の生命予後に影響することから血中PTH値を適切に評価しコントロールする必要がある.PTHアッセイは現在,第二世代(intact PTH),第三世代(whole PTH)が主流となっている.intact PTHは臨床データが豊富なため使用頻度が高いが,複数の固相抗体,標識抗体の認識部位と測定原理が存在するため測定結果が大きく異なること,1-84 PTHのほか,生理活性の異なる7-84 PTHも認識することが問題となる.またintact PTHの程度,腎機能,CKD-MBD治療によりwhole PTHの相関が変化する.whole PTHは理論上もっとも正確にCKD患者の副甲状腺機能を評価できると思われるが,臨床研究からのエビデンスは十分ではなく広く普及していない.PTHアッセイは未だ大きな問題が残されており,引き続き研究会,学会レベルでの前向きな議論が必要であろう.(著者抄録)

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本急性血液浄化学会  

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Language：Japanese   Publisher：(株)東京医学社  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(株)学研メディカル秀潤社  

DOI： 10.15105/J02355.2017209282

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Language：Japanese  

DOI： 10.19020/J01864.2017234015

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

透析患者の疼痛,そう痒は客観的評価が難しく,治療による満足度が大きくないためポリファーマシーの要因となりやすい.各症状に対する処方が過剰となると有害事象が起こるだけでなく,疼痛とそう痒それぞれに対応した処方の相互作用で有害事象となる可能性も考慮しなければならない.対策としては,(1)CKD-MBD,透析条件など疼痛,そう痒の原因となりうる疾患の治療を積極的に行う,(2)疼痛,そう痒の症状に関する治療介入では複数の治療を同時に行わず,一つひとつの治療効果を判断のうえ,継続,変更,追加,使用量の調節など検討する,ことが挙げられる.(著者抄録)

DOI： 10.19020/J01864.2017234015

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Language：Japanese  

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Language：Japanese   Publisher：(NPO)日本急性血液浄化学会  

バスキュラーアクセスカテーテル(カテーテル)は、急性期腎不全患者に有用であるが、カテーテルの血管壁吸引、血栓形成による脱血不良の問題がある。血栓はシリンジで除去できるが、カテーテルが血管壁を吸引する場合は対応が異なりカテーテル位置の調節や生理食塩液のフラッシュにより改善を試みるが、その手順が正しいとは限らない。本研究ではカテーテルの血管壁吸引時にカテーテルの位置調整のみの対処手技有効性評価法の確立を目的とした。カテーテルが血管壁を吸引した状態をモニタリングした報告例は今までないため、ブタ血管を用いてex vivoで血管壁吸引を目視で確認し、手技により改善可能か評価した。手技は、カテーテルの引き抜き方向の移動と回転である。3cm以内の引き抜き方向の移動では、全条件で改善を認めなかった。回転角度を30°ごとに増加するに従い改善の頻度が増加した。本結果は血管壁吸引の改善の可能性を示唆する。(著者抄録)

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Language：Japanese   Publisher：新潟急性血液浄化研究会  

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Language：Japanese   Publisher：新潟県医師会  

心血管病、骨関節疾患、感染症、悪性腫瘍などの慢性腎臓病(CKD)関連疾患には腎障害で増加・蓄積する種々の尿毒症物質が直接的・間接的に作用している。尿毒症物質に着目したCKD関連疾患の病態解明と治療について以下の項目に分けて述べた。1)新潟県と透析療法、2)尿毒症物質、3)β2-ミクログロブリンと透析アミロイドーシス、4)インドキシル硫酸と動脈硬化、5)尿毒症物質の除去効率を向上させる取り組み、として述べた。

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Language：Japanese   Publisher：(株)メディカルトリビューン  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

テリパラチド(副甲状腺ホルモン1-34)は,近年開発された骨粗鬆症治療薬の一つである。非透析患者ではテリパラチドによるアナボリック作用が骨密度の増加,骨折抑制効果が臨床的に明らかにされ,普及している。一方,腎不全,透析患者ではテリパラチドの骨密度増加効果の報告が散見されるが,骨折抑制効果と安全性に関しては,まだ十分検討されていない。骨粗鬆症はCKD-MBD(慢性腎臓病における骨ミネラル代謝異常)と同様に腎不全,透析患者の骨病変の大きな要因の一つであり,安全性を確認した上でテリパラチドをはじめとする骨粗鬆症治療薬の普及が望まれる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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DOI： 10.19020/J02201.2017000630

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Language：Japanese   Publisher：(株)日本メディカルセンター  

透析合併症である透析アミロイドーシスの前駆蛋白質がβ2-ミクログロブリン(β2MG)と同定され30年が経過した.この30年間で基礎的にはアミロイド線維形成・伸長反応の確立とそれに関連する生体分子の提案がなされた.臨床的にはβ2MGの除去効率を向上する透析膜,血液浄化器,血液透析濾過の開発があり,透析アミロイドーシスの発症は減少したという報告もあるが十分とはいえない.近年,変異型β2MGを前駆蛋白質とする遺伝性アミロイドーシス家系の報告やserum amyloid P componentに対する抗体療法が種々の全身性アミロイドーシスに効果的であった報告など,いまだ話題は多く,今後透析アミロイドーシスだけでなくアミロイドーシス全般の機序解明や治療法の開発が進歩すると期待している.(著者抄録)

DOI： 10.19020/J02201.2017000630

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Language：Japanese   Publisher：日本骨形態計測学会  

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)文光堂  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

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Language：Japanese   Publisher：(公財)先進医薬研究振興財団  

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Language：Japanese   Publisher：(株)総合医学社  

＜Point＞透析アミロイドーシス(Aβ2Mアミロイドーシス)とは、全身にAβ2Mアミロイド線維が沈着する疾患であり、その前駆蛋白であるβ2ミクログロブリンが蓄積する疾患ではない。β2ミクログロブリン分子がAβ2Mアミロイド化する機序はわかっておらず、また沈着したAβ2Mアミロイド線維が透析アミロイドーシスを起こす機序もわかっていない。そのモダリティによらず、血清β2ミクログロブリン濃度を低下させる治療はすべて透析アミロイドーシスの症状を緩和させる。血液浄化療法では、腎機能が低下すると全身でほぼ均一に血中濃度が上昇し、それ自体には炎症惹起能力がなく、Aβ2Mアミロイド線維沈着部周囲の炎症細胞を選択的に刺激する作用をもつ、という3つの条件を満たした未知の尿毒物質が除去されている。(著者抄録)

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：日本腎臓学会  

CiNii Article

CiNii Books

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Language：Japanese   Publisher：鈴木謙三記念医科学応用研究財団  

CiNii Article

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Language：Japanese   Publisher：(株)東京医学社  

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Language：Japanese   Publisher：新潟医学会  

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Other Link： http://search.jamas.or.jp/link/ui/2016151274

Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

DOI： 10.1093/ndt/gfv166.20

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

症例は66歳男性で、50歳頃より慢性腎臓病、高血圧症、メタボリック症候群を指摘され、二次性副甲状腺機能亢進症と尿毒症に対し炭酸カルシウム、球形吸着炭を開始した。慢性の便秘があり、腎機能低下で血液透析導入となったが、第4病日より腹部膨満感増強、腹痛が生じた。画像所見で横隔膜挙上、S状結腸から口側の腸管拡張を認め、血圧および動脈血酸素飽和度低下より大腸イレウス、ショックと判断した。腹部は膨隆し続け、膀胱内圧は21mmHgと上昇し、腹部コンパートメント症候群と診断した。下部消化管内視鏡でS状結腸内は球形吸着炭を混じた便塊で満たされ、腸管粘膜は虚血状態にあった。経肛門的に結腸閉鎖を解除できず、緊急開腹術を施行した。開腹直後より呼吸不全は改善し、血圧上昇、自尿流出を認めた。小腸部分切除の後、敗血症合併に対する持続的血液濾過透析と直接血液灌流法を行い、腎機能は改善して第62病日に退院した。

DOI： 10.19020/J01864.2015209953

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Language：Japanese   Publisher：新潟急性血液浄化研究会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：Japanese   Publisher：(一社)日本腎臓学会  

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Language：Japanese   Publisher：(株)学研メディカル秀潤社  

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(株)東京医学社  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY-BLACKWELL  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：OXFORD UNIV PRESS  

Web of Science

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Language：Japanese   Publisher：(一社)日本透析医学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

DOI： 10.19020/J01864.2014064176

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