研究者詳細 - 山本　卓

論文 - 山本　卓

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Appropriate Anthropometric Indices for Geriatric Nutritional Risk Index in Predicting Mortality in Older Japanese Patients: A Comparison of the Lorentz Formula and Body Mass Index. 査読

Kou Kitabayashi, Suguru Yamamoto, Ichiei Narita

The Tohoku journal of experimental medicine 262 ( 4 ) 221 - 228 2024年4月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The Geriatric Nutritional Risk Index (GNRI) is a popular nutritional screening tool. However, the calculation of ideal body weight (IBW) differs among studies. We aimed to compare GNRI calculated using the Lorentz formula (LF) with a body mass index (BMI) and to investigate the cutoffs based on original or quartile criteria for the association with mortality in elderly patients in Japan. This retrospective study enrolled patients aged 65 and older in a long-term care hospital. The GNRI was calculated using two different IBW methods: the LF and a BMI of 22 kg/m2. We categorized GNRI results based on the original criteria or quartile criteria. Mortality outcomes were analyzed using the GNRI based on IBW (LF or BMI) and its classification (original criteria or quartile) through Cox proportional hazard regression. There were 262 participants, including 160 women, with a median age of 86. There was a notable difference between GNRI-BMI and GNRI-LF. The GNRI-LF original and quartile criteria did not show an association with mortality. A significant association with mortality was found between Q1 and Q4 in the GNRI-BMI quartile criteria (hazard ratio: 2.60; 95% confidence interval: 1.66-4.07, p < 0.01), but not the GNRI-BMI original criteria. The GNRI calculated using BMI with quartile criteria proved to be a reliable predictor of mortality for Japanese elderly inpatients. The calculation method of GNRI and the appropriate cutoff point should be considered based on the patient's background.

DOI： 10.1620/tjem.2024.J001

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Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS. 査読国際誌

Suguru Yamamoto, Hanne Skou Jørgensen, Junhui Zhao, Angelo Karaboyas, Hirotaka Komaba, Marc Vervloet, Sandro Mazzaferro, Etienne Cavalier, Brian Bieber, Bruce Robinson, Pieter Evenepoel, Masafumi Fukagawa

Kidney international reports 9 ( 4 ) 863 - 876 2024年4月

Low muscle strength and physical function contribute to falls in hemodialysis patients, but not muscle mass. 査読

Nobuyuki Shirai, Suguru Yamamoto, Yutaka Osawa, Atsuhiro Tsubaki, Shinichiro Morishita, Tsubasa Sugahara, Ichiei Narita

Clinical and experimental nephrology 28 ( 1 ) 67 - 74 2024年1月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Patients on hemodialysis (HD) have a higher incidence of fractures than the general population. Sarcopenia is frequently observed in patients on HD; however, the association of falls with sarcopenia and its diagnostic factors, including muscle mass, muscle strength, and physical function, are incompletely understood. METHODS: This prospective cohort study was conducted at a single center. Sarcopenia was assessed according to the 2019 Asian Working Group for Sarcopenia diagnostic criteria. Muscle mass was measured the bioelectrical impedance method. Grip strength was evaluated to assess muscle strength, while the Short Physical Performance Battery (SPPB) was used to assess physical function. Falls and their detailed information were surveyed every other week. RESULTS: This study analyzed 65 HD patients (median age, 74.5 [67.5-80.0] years; 33 women [49.2%]). Sarcopenia was diagnosed in 36 (55.4%) patients. During the 1-year observation period, 31 (47.7%) patients experienced accidental falls. The falls group had lower median grip strength than the non-falls group (14.7 [11.4-21.8] kg vs. 22.2 [17.9-27.6] kg; p < 0.001). The median SPPB score was also lower in the falls versus non-falls group (7.0 [5.0-11.0] vs. 11.0 [8.0-12.0]; p = 0.009). In adjusted multiple regression analysis, diagnostic factors, including grip strength (B = 0.96, p = 0.04, R2 = 0.19) and SPPB (B = 1.11, p = 0.006, R2 = 0.23), but not muscle mass, were independently associated with fall frequency. CONCLUSIONS: The frequency of falls in HD patients was related to muscle strength and physical function, but not muscle mass.

DOI： 10.1007/s10157-023-02403-4

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Pruritus and protein-bound uremic toxins in patients undergoing hemodialysis: a cross-sectional study. 国際誌

Suguru Yamamoto, Takahiro Tanaka, Kentaro Omori, Isei Ei, Kaori Kikuchi, Ayano Konagai, Shin Goto, Nobutaka Kitamura, Ichiei Narita

Clinical kidney journal 17 ( 1 ) sfae007 2024年1月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Patients undergoing hemodialysis frequently experience pruritus; its severity is associated with poor quality of life and mortality. Recent progress in hemodialysis treatment has improved the removal of small- and middle-molecular-weight molecules; however, the removal of protein-bound uremic toxins (PBUTs) remains difficult. It is possible that pruritus is associated with serum PBUTs in patients undergoing hemodialysis. METHODS: We conducted a multicenter cross-sectional study in patients undergoing hemodialysis (n = 135). The severity of pruritus was assessed using the 5D-itch scale and medication use. Serum PBUTs, including indoxyl sulfate, p-cresyl sulfate, indole acetic acid, phenyl sulfate, and hippuric acid, were measured using mass spectrometry; the PBUT score was calculated from these toxins using principal component analysis. Univariate and multiple regression analyses were performed to examine independent predictors of pruritus. RESULTS: Pruritus was reported by 62.2%, 21.5%, and 13.3%, 1.5% and 0.7% as 5 (not at all), 6-10, 11-15, 16-20, and 21-25 points, respectively. The PBUT score was higher in patients undergoing dialysis having pruritus than those without pruritus (0.201 [-0.021 to 0.424] vs -0.120 [-0.326 to 0.087]; P = 0.046). The PBUT score was shown to have an association with the presence of pruritus (coefficient 0.498[Formula: see text]0.225, odds ratio: 1.65 [1.06-2.56]; P = 0.027). CONCLUSION: Uremic pruritus was frequently found and associated with the PBUT score in patients undergoing hemodialysis. Further studies are required to clarify the impact of PBUTs on uremic pruritus and to explore therapeutic strategies in patients undergoing hemodialysis.

DOI： 10.1093/ckj/sfae007

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Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study. 査読国際誌

Shiori Yoshida, Suguru Yamamoto, Daisuke Miyauchi, Ryohei Terashima, Atsushi Hashimoto, Haruna Miyazawa, Takahiro Tanaka, Masahiro Ishizawa, Mototsugu Tanaka, Yoshihiko Tomita, Ikuo Aoike, Shin Goto, Ichiei Narita

Blood purification 53 ( 2 ) 123 - 129 2024年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan. Polymethylmethacrylate (PMMA) membranes can remove medium- to high-molecular-weight proteins by adsorption. This study aimed to assess the efficacy of removing medium- to high-molecular-weight proteins, such as α1-m and β2-microglobulin (β2-m), through post-dilution OL-HDF with PMMA (Post-PMMA). The assessment was conducted in comparison to pre-dilution OL-HDF with PS (Pre-PS), using an open-label, single-arm study. METHODS: Seven patients with ESKD on Pre-PS underwent Post-PMMA with replacement volume of 30 mL/min (low flow) and 50 mL/min (high flow). Clearance and removal rates of α1-m, β2-m, small molecules, inflammatory cytokines, and albumin were measured at 60 and 240 min of treatment. RESULTS: Clearance rates of α1-m at 60 min were -2.8 ± 5.2 mL/min with Pre-PS, -0.4 ± 2.6 mL/min with Post-PMMA (low), and 0.6 ± 3.4 mL/min with Post-PMMA (high). The removal rate of α1-m was higher in Post-PMMA than that in Pre-HDF-PS (Post-PMMA [high] 17.7 ± 5.9%, Post-PMMA [low] 15.0 ± 5.6%, and Pre-PS 4.1 ± 5.5%). Adsorption clearance of β2-m was increased with Post-PMMA. Albumin leakage in Post-PMMA was not higher than that in Pre-PS. CONCLUSION: The removal rate of α1-m with Post-PMMA was higher than that with Pre-PS. The PMMA membrane adsorbed β2-m, suggesting the removal effect of medium- to high-molecular-weight proteins by the adsorption method. Since Post-PMMA effectively removes α1-m without excessive albumin leakage, it will be useful for patients with ESKD, especially those with a poor nutritional status.

DOI： 10.1159/000534459

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Dynamic and static balance functions in hemodialysis patients and non-dialysis dependent CKD patients. 査読国際誌

Nobuyuki Shirai, Suguru Yamamoto, Yutaka Osawa, Atsuhiro Tsubaki, Shinichiro Morishita, Ichiei Narita

Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 27 ( 3 ) 412 - 418 2023年6月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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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プロテオーム解析招待

羽深将人, 山本卓, 内木宏延, 山本格, 成田一衛

64 ( 8 ) 863 - 867 2022年12月

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis. 査読国際誌

Kichitaro Nakajima, Keiichi Yamaguchi, Masahiro Noji, César Aguirre, Kensuke Ikenaka, Hideki Mochizuki, Lianjie Zhou, Hirotsugu Ogi, Toru Ito, Ichiei Narita, Fumitake Gejyo, Hironobu Naiki, Suguru Yamamoto, Yuji Goto

Nature communications 13 ( 1 ) 5689 - 5689 2022年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cold Spring Harbor Laboratory

Abstract

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β<sub>2</sub>-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： 10.1038/s41467-022-33247-3

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Association of the nutritional risk index for Japanese hemodialysis with mortality and dietary nutritional intake in patients undergoing hemodialysis during long-term hospitalization. 査読

26 ( 12 ) 1200 - 1207 2022年8月

Relationship between Nutrition-Related Problems and Falls in Hemodialysis Patients: A Narrative Review. 査読国際誌

Nobuyuki Shirai, Tatsuro Inoue, Masato Ogawa, Masatsugu Okamura, Shinichiro Morishita, Yamamoto Suguru, Atsuhiro Tsubaki

Nutrients 14 ( 15 ) 3225 - 3225 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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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Magnesium intake by enteral formulation affects serum magnesium concentration in patients undergoing hemodialysis. 査読国際誌

Kou Kitabayashi, Suguru Yamamoto, Ichiei Narita

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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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Dysfunction in dynamic, but not static balance is associated with risk of accidental falls in hemodialysis patients: a prospective cohort study. 査読国際誌

Nobuyuki Shirai, Suguru Yamamoto, Yutaka Osawa, Atsuhiro Tsubaki, Shinichiro Morishita, Ichiei Narita

BMC nephrology 23 ( 1 ) 237 - 237 2022年7月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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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Medical Director Practice of Advising Increased Dietary Protein Intake in Hemodialysis Patients With Hyperphosphatemia: Associations With Mortality in the Dialysis Outcomes and Practice Patterns Study. 査読国際誌

Suguru Yamamoto, Brian A Bieber, Hirotaka Komaba, Norio Hanafusa, Hiroki Kitabayashi, Takanobu Nomura, Aleix Cases, Christian Combe, Ronald L Pisoni, Bruce M Robinson, Masafumi Fukagawa

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation 32 ( 2 ) 243 - 250 2022年3月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Elsevier BV

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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Fear of falling and physical activity in hemodialysis patients: a pilot study 査読

Suguru Yamamoto

Renal Replacement Therapy 7 63 2021年11月

Comparison of muscle strength between hemodialysis patients and non-dialysis patients with chronic kidney disease. 査読

Nobuyuki Shirai, Suguru Yamamoto, Yutaka Osawa, Atsuhiro Tsubaki, Shinichiro Morishita, Kanami Igarashi, Ichiei Narita

Journal of physical therapy science 33 ( 10 ) 742 - 747 2021年10月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

[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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Locomotive syndrome in hemodialysis patients and its association with quality of life-a cross-sectional study 査読

Suguru Yamamoto

Renal Replacement Therapy 7 36 2021年6月

Serum total indoxyl sulfate and clinical outcomes in hemodialysis patients: results from the Japan Dialysis Outcomes and Practice Patterns Study. 査読国際誌

Suguru Yamamoto, Douglas S Fuller, Hirotaka Komaba, Takanobu Nomura, Ziad A Massy, Brian Bieber, Bruce Robinson, Ronald Pisoni, Masafumi Fukagawa

Clinical kidney journal 14 ( 4 ) 1236 - 1243 2021年4月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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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pH-Dependent Protein Binding Properties of Uremic Toxins In Vitro. 査読国際誌

Suguru Yamamoto, Kenichi Sasahara, Mio Domon, Keiichi Yamaguchi, Toru Ito, Shin Goto, Yuji Goto, Ichiei Narita

Toxins 13 ( 2 ) 116 - 116 2021年2月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

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 < 4 or >12, and weakened interaction with IS occurred at pH < 5 or >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 potentiates lipopolysaccharide-induced macrophage inflammatory response. 査読国際誌

Toru Ito, Suguru Yamamoto, Keiichi Yamaguchi, Mami Sato, Yoshikatsu Kaneko, Shin Goto, Yuji Goto, Ichiei Narita

The Journal of biological chemistry 295 ( 12 ) 4014 - 4023 2020年3月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

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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Adsorption of Protein-Bound Uremic Toxins Using Activated Carbon through Direct Hemoperfusion in vitro 査読

Suguru Yamamoto, Toru Ito, Mami Sato, Shin Goto, Junichiro J. Kazama, Fumitake Gejyo, Ichiei Narita

Blood Purification 48 ( 3 ) 215 - 222 2019年

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