研究者詳細 - 内田　治仁

論文 - 内田　治仁

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フェブキソスタットによる尿酸低下が血管機能に与える影響の検討

松岡奈津実, 内田治仁, 前島洋平, 雛元紀和, 浅野健一郎, 大西康博, 岡本修吾, 西脇麻里子, 秦昌紫子, 武本梨佳, 大高望, 北川正史, 和田淳

日本高血圧学会総会プログラム・抄録集 42回 368 - 368 2019年10月

18歳時に経皮的腎動脈形成術を行い10年以上経過して血圧上昇をきたした高安動脈炎の1例

内田治仁, 戸田洋伸, 藤本竜一, 大塚寛昭, 花山宜久, 武本梨佳, 大西康博, 高杉佳奈子, 梅林亮子, 吉田賢司, 和田淳

脈管学 59 ( Suppl. ) S226 - S226 2019年10月

PAD患者におけるTotal Vascular ResistanceおよびAugmentation Pressureに関する検討

内田治仁, 武本梨佳, 松岡奈津美, 大西康博, 岡本修吾, 西脇麻里子, 秦昌紫子, 大高望, 戸田洋伸, 北川正史, 和田淳

日本高血圧学会総会プログラム・抄録集 42回 348 - 348 2019年10月

Impaired mental health status in patients with chronic kidney disease is associated with estimated glomerular filtration rate decline. 査読国際誌

Yasuhiro Onishi, Haruhito A Uchida, Hidemi Takeuchi, Yuki Kakio, Hitoshi Sugiyama, Jun Wada, Noriaki Shimada, Hironobu Tokumasu, Masaki Fukushima, Kenichiro Asano

Nephrology (Carlton, Vic.) 24 ( 9 ) 926 - 932 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Deteriorated health-related quality of life (HRQOL) is associated with increased risk for death in both chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients; however, the impact of HRQOL on CKD progression is not well investigated. METHODS: We aimed to evaluate the association between HRQOL and CKD progression in Japanese patients with CKD. One hundred and three outpatients who visited the department of nephrology at our hospital (mean estimated glomerular filtration rate (eGFR); 32.1 ± 11.2 mL/min per 1.73 m2 ) between April 2007 and March 2012 were enrolled in this study. The primary outcome was 30% decline of eGFR or ESRD. We assessed HRQOL of all participants at baseline, including the physical component summary (PCS), the mental component summary (MCS) and the role/social component summary (RCS), using SF-36. Based on the baseline score of PCS, MCS and RCS, we divided all subjects into two groups by median. RESULTS: We studied 66 men (64.1%) and 37 women aged 61.7 ± 10.0 years old. During approximately 2.5 years of follow-up period, 59 patients (57.3%) reached 30% eGFR decline or ESRD. Cox regression analyses demonstrated that lower MCS score was significantly associated with CKD progression (hazard ratio (HR) = 1.83, 95% CI = 1.04-3.21, P = 0.035), but that lower PCS score and RCS score were not (HR = 0.70, 95% CI = 0.39-1.25, P = 0.223; HR = 0.95, 95% CI = 0.54-1.67, P = 0.854, respectively). CONCLUSION: We found that impaired mental health was associated with CKD progression. The evaluation of the mental health should be performed in the patients with CKD.

DOI： 10.1111/nep.13515

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A Patient with Type 3 Autoimmune Polyglandular Syndrome who Developed Systemic Lupus Erythematosus 8 years after the Diagnosis of Autoimmune Hepatitis. 査読

Tomoyo Mifune-Morioka, Haruhito A Uchida, Kazuhiko Fukushima, Mayu Watanabe, Chihiro Ouchi, Koki Mise, Chieko Kawakita, Yuzuki Kano, Akifumi Onishi, Kishio Toma, Jun Eguchi, Nozomu Wada, Fusao Ikeda, Erika Sasaki, Yu Suganami, Masayuki Kishida, Hitoshi Sugiyama, Hiroyuki Okada, Jun Wada

Acta medica Okayama 73 ( 4 ) 367 - 372 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Eight years prior to her present admission, a 61-year-old Japanese woman was diagnosed with autoimmune hepatitis, slowly progressive insulin-dependent diabetes mellitus, and chronic thyroiditis; she had been treated with oral prednisolone (PSL). After she suddenly discontinued PSL, she newly developed systemic lupus erythematosus. A combination therapy of oral PSL and intravenous cyclophosphamide resulted in remission. She was finally diagnosed with autoimmune polyglandular syndrome (APS) type 3 (3A ,3B, 3D), complicated with four different autoimmune diseases. Since patients with type 3 APS may present many manifestations over a long period of time, they should be carefully monitored.

DOI： 10.18926/AMO/56940

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Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease. 査読

Hironobu Toda, Haruhito Uchida, Kazufumi Nakamura, Hidemi Takeuchi, Masaru Kinomura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Jun Wada, Hiroshi Ito

Internal medicine (Tokyo, Japan) 58 ( 13 ) 1917 - 1922 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

DOI： 10.2169/internalmedicine.2076-18

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血管内皮細胞における細胞老化に対するクロロゲン酸の及ぼす影響の検討

秦昌紫子, 内田治仁, 大高望, 大西康博, 和田淳

日本動脈硬化学会総会プログラム・抄録集 51回 1 - 5 2019年7月

Osteomalacia and Fanconi Syndrome Induced by Adefovir. 査読

Natsumi Matsuoka, Haruhito A Uchida, Yoshikazu Hara, Hiroto Matsuda

Internal medicine (Tokyo, Japan) 58 ( 11 ) 1659 - 1659 2019年6月

The clinical efficacy of angiotensin II type1 receptor blockers on inflammatory markers in patients with hypertension: a multicenter randomized-controlled trial; MUSCAT-3 study. 査読国際誌

Ryoko Umebayashi, Haruhito A Uchida, Yuka Okuyama, Yuki Kakio, Yoshihisa Hanayama, Kenichi Shikata, Jun Wada

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 24 ( 3 ) 255 - 261 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Purpose: The purpose of present study was to evaluate the clinical efficacy of irbesartan on the anti-inflammatory and anti-oxidative stress effect in patients with hypertension compared to other ARBs. Further, we assessed the effect of the ARBs on kidney function and urinary albumin excretion. Methods: Eighty-five outpatients with hypertension who took an ARB except irbesartan more than 3 months were assigned into two groups, one continued the same ARB and the other switched the ARB to irbesartan for 6 months. Results: Although blood pressures were equally controlled (continue group: 148 ± 2/79 ± 2 mmHg to 131 ± 2/74 ± 2 mmHg; switch group: 152 ± 2/81 ± 2 mmHg to 132 ± 2/74 ± 2 mmHg; p < 0.001 each), the inflammatory markers (hsCRP, PTX3, MCP-1) and oxidative stress marker (MDA-LDL) did not change after 6 months in both groups. Urinary albumin excretion was significantly reduced only in the switch group without renal function deterioration (switch group 292.4 ± 857.9 mg/gCr to 250.6 ± 906.5 mg/gCr, p = 0.012). Conclusion: These results provide knowledge of the characteristics of irbesartan, suggesting appropriate choice of ARBs in the treatment for hypertension should be considered.

DOI： 10.1080/1354750X.2018.1548033

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岡山市CKDネットワーク(OCKD-NET)におけるCKD病診連携8年後の追跡調査

大西康博, 内田治仁, 大高望, 田邊克幸, 森永裕士, 木野村賢, 前島洋平, 杉山斉, 太田康介, 丸山啓輔, 平松信, 大城義之, 森岡茂, 福島正樹, 和田淳

日本腎臓学会誌 61 ( 3 ) 388 - 388 2019年5月

当院で腹膜透析を導入した多発性嚢胞腎患者に関する検討

大西康博, 田邊克幸, 大高望, 大西章史, 北川正史, 森永裕士, 木野村賢, 内田治仁, 杉山斉, 和田淳

日本透析医学会雑誌 52 ( Suppl.1 ) 549 - 549 2019年5月

Higher Serum Testosterone Levels Associated with Favorable Prognosis in Enzalutamide- and Abiraterone-Treated Castration-Resistant Prostate Cancer. 査読国際誌

Shinichi Sakamoto, Maihulan Maimaiti, Minhui Xu, Shuhei Kamada, Yasutaka Yamada, Hiroki Kitoh, Hiroaki Matsumoto, Nobuyoshi Takeuchi, Kosuke Higuchi, Haruhito A Uchida, Akira Komiya, Maki Nagata, Hiroomi Nakatsu, Hideyasu Matsuyama, Koichiro Akakura, Tomohiko Ichikawa

Journal of clinical medicine 8 ( 4 ) 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Testosterone plays a significant role in maintaining the tumor microenvironment. The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied. In total, 107 patients treated with Enza and/or Abi at Chiba University Hospital and affiliated hospitals were studied. The relationships between progression-free survival (PFS), overall survival (OS), and clinical factors were studied by Cox proportional hazard and Kaplan-Meier models. In the Abi and Enza groups overall, TST ≥ 13 ng/dL (median) (Hazard Ratio (HR) 0.43, p = 0.0032) remained an independent prognostic factor for PFS. In the Enza group, TST ≥ 13 ng/dL (median) was found to be a significant prognostic factor (HR 0.28, p = 0.0044), while, in the Abi group, TST ≥ 12 ng/dL (median) was not significant (HR 0.40, p = 0.0891). TST showed significant correlation with PFS periods (r = 0. 32, p = 0.0067), whereas, for OS, TST ≥ 13 ng/dL (median) showed no significant difference in the Abi and Enza groups overall. According to Kaplan-Meier analysis, a longer PFS at first-line therapy showed a favorable prognosis in the Enza group (p = 0.0429), while no difference was observed in the Abi group (p = 0.6051). The TST level and PFS of first-line therapy may be considered when determining the treatment strategy for CRPC patients.

DOI： 10.3390/jcm8040489

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Exogenous Vasohibin-2 Exacerbates Angiotensin II-Induced Ascending Aortic Dilation in Mice. 査読

Michihiro Okuyama, Haruhito A Uchida, Yoshiko Hada, Yuki Kakio, Nozomu Otaka, Ryoko Umebayashi, Katsuyuki Tanabe, Yasuhiro Fujii, Shingo Kasahara, Venkateswaran Subramanian, Alan Daugherty, Yasufumi Sato, Jun Wada

Circulation reports 1 ( 4 ) 155 - 161 2019年4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：Japanese Circulation Society

Background: Chronic angiotensin II (AngII) infusion promotes ascending aortic dilation in C57BL/6J mice. Meanwhile, vasohibin-2 (VASH2) is an angiogenesis promoter in neovascularization under various pathologic conditions. The aim of this study was to investigate whether exogenous VASH2 influences chronic AngII-induced ascending aortic dilation. Methods and Results: Eight-ten-week-old male C57BL/6J mice were injected with adenovirus (Ad) expressing either VASH2 or LacZ. One week after the injection, mice were infused with either AngII or saline s.c. for 3 weeks. Mice were divided into 4 groups: AngII+VASH2, AngII+LacZ, saline+VASH2, and saline+LacZ. Overexpression of VASH2 significantly increased AngII-induced intimal areas as well as the external diameter of the ascending aorta. In addition, VASH2 overexpression promoted ascending aortic medial elastin fragmentation in AngII-infused mice, which was associated with increased matrix metalloproteinase activity and medial smooth muscle cell (SMC) apoptosis. On western blot analysis, accumulation of apoptotic signaling proteins, p21 and p53 was increased in the AngII+VASH2 group. Furthermore, transfection of human aortic SMC with Ad VASH2 increased p21 and p53 protein abundance upon AngII stimulation. Positive TUNEL staining was also detected in the same group of the human aortic SMC. Conclusions: Exogenous VASH2 exacerbates AngII-induced ascending aortic dilation in vivo, which is associated with increased medial apoptosis and elastin fragmentation.

DOI： 10.1253/circrep.CR-19-0008

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The relationship between repeated measurement of casual and 24-h urinary sodium-to-potassium ratio in patients with chronic kidney disease. 査読国際誌

Yuka Okuyama, Haruhito A Uchida, Toshiyuki Iwahori, Hiroyoshi Segawa, Ayako Kato, Hidemi Takeuchi, Yuki Kakio, Ryoko Umebayashi, Masashi Kitagawa, Hitoshi Sugiyama, Katsuyuki Miura, Hirotsugu Ueshima, Jun Wada

Journal of human hypertension 33 ( 4 ) 286 - 297 2019年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study aimed to clarify the relationship between repeated measurements of casual (spot) and 24-h urinary sodium-to-potassium (Na/K) ratios in patients with chronic kidney disease (CKD). A total of 61 inpatients with CKD, 31 in stage 1-3 (eGFR [estimated glomerular filtration rate] ≥ 30 ml/min/1.73 m2) and 30 in stage 4-5 (eGFR < 30 ml/min/1.73 m2), aged 20-85 consuming a low-sodium diet (NaCl [sodium chloride] 6 g/day) were recruited. Urinary Na, K, and Na/K ratios were measured in both casual urine samples and 2-day, 24 h urine samples, and then analyzed by correlation and Bland-Altman analyses. Mean 24-h urine Na/K ratio was higher in participants in stage 4-5 (5.1) than in participants in stage 1-3 (4.1) CKD. Casual urine Na/K ratio was strongly correlated with 2-day, 24-h urine Na/K ratio by sampling 4 casual urine specimens every morning and evening in participants in stage 1-3 (r = 0.69-0.78), but not in stage 4-5 (r = 0.12-0.19). The bias for mean Na/K ratio between 2-day, 24-h urine, and the 4 casual urine sampling ranged from -0.86 to 0.16 in participants in stage 1-3, and the quality of agreement for the mean of this casual urine sampling was similar to that of sampling 8 casual urine samples for estimating 2-day, 24-h values. Methods using repeated casual urine Na/K ratios may provide a reasonable estimation of 24-h urine Na/K ratio in normotensive and hypertensive as well as individuals with stage 1-3, but not stage 4-5 CKD.

DOI： 10.1038/s41371-018-0127-1

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Urine 5MedC, a Marker of DNA Methylation, in the Progression of Chronic Kidney Disease. 査読国際誌

Akifumi Onishi, Hitoshi Sugiyama, Masashi Kitagawa, Toshio Yamanari, Keiko Tanaka, Ayu Ogawa-Akiyama, Yuzuki Kano, Koki Mise, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Haruhito A Uchida, Jun Wada

Disease markers 2019 5432453 - 5432453 2019年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Alterations in DNA methylation may be involved in disease progression in patients with chronic kidney disease (CKD). Recent studies have suggested that 5-methyl-2'-deoxycytidine (5MedC) may be a marker of hypermethylation of DNA. Currently, there is no information available regarding the urine levels of 5MedC and its association with the progression of CKD. Method: We examined the urine levels of 5MedC in spot urine samples from 308 patients with CKD (median age: 56 years, male: 53.2%, and glomerulonephritis: 51.0%) using a competitive enzyme-linked immunosorbent assay and investigated the relationships among urine 5MedC, urine albumin, urine α1-microglobulin (α1MG), and the laboratory parameters associated with CKD. The patients were followed for three years to evaluate renal endpoints in a prospective manner. Results: The urine 5MedC level was significantly increased in the later stages of CKD compared to the early to middle stages of CKD. In multiple logistic regression models, urine 5MedC was significantly associated with the prediction of later CKD stages. Urine 5MedC (median value, 65.9 μmol/gCr) was significantly able to predict a 30% decline in the estimated GFR or a development of end-stage renal disease when combined with macroalbuminuria or an increased level of urine α1MG (median value, 5.7 mg/gCr). Conclusion: The present data demonstrate that the urine 5MedC level is associated with a reduced renal function and can serve as a novel and potent biomarker for predicting the renal outcome in CKD patients. Further studies will be necessary to elucidate the role of urine DNA methylation in the progression of CKD.

DOI： 10.1155/2019/5432453

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Report of health checkup system for chronic kidney disease in general population in Okayama city: effect of health guidance intervention on chronic kidney disease outcome. 査読国際誌

Yuki Kakio, Haruhito A Uchida, Hidemi Takeuchi, Yuka Okuyama, Ryoko Umebayashi, Hiroyuki Watatani, Yohei Maeshima, Hitoshi Sugiyama, Jun Wada

International journal of nephrology and renovascular disease 12 143 - 152 2019年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: From 2011, Okayama municipal government started the health checkup follow-up project to find those who were unaware of suffering chronic kidney disease and to prevent from aggravation of CKD stage. In this study, we aimed to evaluate the effect of 2 years' CKD-follow-up project regarding renal function and CKD risks. Patients and methods: Those who received a health checkup by the national health insurance in Okayama city in 2011 were recruited. The patients with lifestyle-related diseases or metabolic syndrome were excluded. Subjects who had an estimated glomerular filtration rate<50 mL/min/1.73 m2 or urinary protein positive by dipstick test were defined as compromised renal function group. They were recommended to visit a medical institution. Non-compromised renal function participants with two or more risks for CKD (hyperglycemia, higher blood pressure, dyslipidemia, hyperuricemia) were recommended to receive a health guidance (risk group). The change of renal function and CKD risks between 2011 and 2013 in each group was examined. Results: A total of 28,309 people received a health checkup in 2011. In compromised renal function group, 39.5% (96/243) of the subjects improved their CKD stages in 2013 regardless of the visit of medical institutions or the frequency of receiving health checkup. In risk group, 63.4% (260/410) of the subjects decreased their CKD risks in 2013 independent of the reception of health guidance. Conclusion: In both compromised renal function group and risk group, more than half of subjects kept their kidney function (217/243) and decreased the number of CKD risks (260/410) in 2 years' follow-up. Receiving a health checkup itself and notification of one's own health condition could exert a protective effect on kidney function.

DOI： 10.2147/IJNRD.S198781

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Abdominal aortic aneurysm in aged population. 査読国際誌

Ryoko Umebayashi, Haruhito A Uchida, Jun Wada

Aging 10 ( 12 ) 3650 - 3651 2018年12月

Diabetic nephropathy is associated with frailty in patients with chronic hemodialysis. 査読

Yuki Kakio, Haruhito A Uchida, Hidemi Takeuchi, Yuka Okuyama, Michihiro Okuyama, Ryoko Umebayashi, Kentaro Wada, Hitoshi Sugiyama, Ken Sugimoto, Hiromi Rakugi, Shingo Kasahara, Jun Wada

Geriatrics & gerontology international 18 ( 12 ) 1597 - 1602 2018年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Since 1998, the leading cause of chronic hemodialysis in Japan has been diabetic nephropathy. Diabetes mellitus is known to be a risk factor for frailty, but it still remains unknown whether diabetic nephropathy is associated with frailty in chronic dialysis patients. The authors carried out the present study to reveal the association between frailty and diabetic nephropathy in chronic hemodialysis patients. METHODS: A total of 355 patients who were on hemodialysis were recruited. Participants were divided into two groups of either patients who suffered diabetic nephropathy with end-stage renal disease (DN group, n = 150) or not (Non-DN group, n = 205). The authors investigated the difference of the prevalence of frailty between the two groups. Furthermore, the authors examined the risk factors for frailty. RESULTS: The prevalence of frailty in the DN group was significantly higher than that in the Non-DN group (28.0% vs 16.5%, P = 0.0161). To evaluate the association between frailty and its risk factors, we compared frail patients (n = 71) and non-frail patients (n = 262). After adjusting their interrelationships by using multivariate logistic regression analysis, diabetic nephropathy was determined as a significant risk factor for frailty. CONCLUSIONS: The authors found the close association between frailty and diabetic nephropathy in chronic hemodialysis patients. Geriatr Gerontol Int 2018; 18: 1597-1602.

DOI： 10.1111/ggi.13534

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Chronic kidney disease is associated with carotid atherosclerosis and symptomatic ischaemic stroke. 査読国際誌

Nobuo Kajitani, Haruhito A Uchida, Isao Suminoe, Yuki Kakio, Masashi Kitagawa, Hajime Sato, Jun Wada

The Journal of international medical research 46 ( 9 ) 3873 - 3883 2018年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective We aimed to investigate the relationships among chronic kidney disease (CKD), symptomatic ischaemic stroke, and carotid atherosclerosis. Methods We enrolled 455 patients who underwent carotid ultrasonography in our hospital, including 311 patients with symptomatic ischaemic stroke and 144 patients without symptomatic ischaemic stroke. Carotid intima-media thickness (IMT), the rate of internal carotid artery stenosis, and maximal plaque size were evaluated. Results The mean age of the patients was 68.5 ± 11.0 years and the mean estimated glomerular filtration rate (eGFR) was 68.8 ± 18.2 mL/min/1.73 m2. After adjustment for cardiovascular risk factors, the mean IMT was significantly higher in patients with CKD than in those without CKD. The IMT and eGFR were negatively correlated in patients with stroke (r = -0.169). Multiple logistic regression analyses showed that mean IMT, plaque size, and internal carotid artery stenosis were significant determinants of symptomatic ischaemic stroke after adjustment of multivariate risk factors. Furthermore, the eGFR was a negative determinant of symptomatic ischaemic stroke after adjusting for classical risk factors (odds ratio [95% confidence interval] = 0.868 [0.769-0.979]). Conclusion CKD might be associated with the carotid atherosclerosis and symptomatic ischaemic stroke.

DOI： 10.1177/0300060518781619

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末梢動脈疾患が中心血圧、aPWV、AIに与える影響の検討

武本梨佳, 内田治仁, 垣尾勇樹, 大高望, 大西康博, 秦昌紫子, 北川正史, 戸田洋伸, 吉田賢司, 大塚文男, 杉山斉, 伊藤浩, 和田淳

日本高血圧学会総会プログラム・抄録集 41回 PM01 - 03 2018年9月

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