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Papers - ITOH Hiroshi

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Difficulty in managing nephrotic syndrome-associated cerebral venous thrombosis.

Takashin Nakayama, Ryunosuke Mitsuno, Takuto Torimitsu, Norifumi Yoshimoto, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh

CEN case reports 10 ( 1 ) 132 - 138 2021.02

ISSN 2192-4449

Thromboembolism is one of the most serious complications of nephrotic syndrome (NS). Although the occurrence of renal vein thrombosis or deep vein thrombosis is well recognized in NS patients, they rarely develop cerebral venous thrombosis (CVT). The mortality rate of CVT patients is still approximately 10%, and 6-10% of patients who survive have a severe and permanent disability. Herein, we report the case of a 26-year-old woman with multiple thrombotic risk factors, including the presence of NS, use of oral contraceptives, smoking, and alcohol consumption who developed wide-range CVT. Undetermined fraction heparin, albumin and AT-III transfusion, and direct mechanical catheter thrombectomy were insufficient for the improvement of CVT. However, CVT eventually improved along with the remission of NS by prednisolone administration. This process indicates that in the management of CVT associated with NS, it is crucial to control the activity of NS. Currently, knowledge on the treatment for NS associated with CVT is limited, and this is a subject of urgent investigation.

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Effects of High Glucose and Lipotoxicity on Diabetic Podocytes.

Ran Nakamichi, Kaori Hayashi, Hiroshi Itoh

Nutrients 13 ( 1 ) 1 - 11 2021.01

Glomerular podocytes are highly differentiated cells that cover glomerular capillaries from the outside and have a characteristic morphology with numerous foot processes. The formation of slit membranes between the foot processes serves as a final filtration barrier for urine filtration from the blood. Podocyte damage causes disruption of the slit membrane, subsequent proteinuria and finally glomerulosclerosis, which is a common pathway in various types of chronic kidney disease (CKD). In recent years, there has been an increase in diabetes, due to rapid lifestyle changes, which is the main cause of CKD. Therefore, understanding the effect of diabetic status on podocytes is of great importance to establish a strategy for preventing CKD progression. In this review, we summarize altered glucose and lipid metabolism in diabetic podocytes and also discuss the reversibility of the changes in podocyte phenotype.

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A Case of New-Onset Systemic Lupus Erythematosus With Serositis in a Maintenance Hemodialysis Patient.

Shotaro Kosugi, Tadashi Yoshida, Norifumi Yoshimoto, Hiroshi Itoh, Mototsugu Oya

Clinical medicine insights. Case reports 14 11795476211056172 - 11795476211056172 2021

ISSN 1179-5476

A 61-year-old woman with a 4-year history of maintenance hemodialysis due to end-stage renal disease of unknown cause was admitted because of a recurrent fever and abdominal pain lasting for 3 months. She had rheumatoid arthritis as a complication and had taken sulfasalazine for over 4 years. Laboratory data revealed thrombocytopenia, hypocomplementemia, a high C-reactive protein level, and positivity for antinuclear antibody and anti-double strand DNA antibody. Gallium scintigraphy showed pericarditis, pleuritis, and peritonitis. Nonscarring alopecia was also noted. She was diagnosed as having systemic lupus erythematosus (SLE). Drug-induced lupus elicited by sulfasalazine was ruled out because the symptoms did not improve even after the discontinuation of the drug upon admission. Oral prednisolone treatment markedly improved her symptoms and laboratory data. However, she later died of sepsis arising from proctitis on day 71 of admission. This report underscores the necessity of considering new-onset SLE in patients with unexplained fever and serositis, including pleuritis, peritonitis, or pericarditis, even if they are receiving maintenance dialysis.

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Bullous pemphigoid in patients receiving peritoneal dialysis: a case series and a literature survey.

Kohkichi Morimoto, Tadashi Yoshida, Naoki Washida, Kiyotaka Uchiyama, Takashin Nakayama, Hiroshi Itoh, Mototsugu Oya

Renal failure 43 ( 1 ) 651 - 657 2021

ISSN 0886022X

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Although several cases of BP in end-stage renal disease patients receiving peritoneal dialysis (PD) or hemodialysis have been reported, the incidence of BP in these patients remains unknown. We recently experienced three PD patients diagnosed with BP. The skin injury was likely to be a trigger of BP in all the three PD patients. Nifedipine and icodextrin exposures were possible factors directly or indirectly affecting the onset of BP, because they were common in the three cases. We also report that the incidence of BP in PD patients was 3/478.3 person-years in a single-center 10-year study. This case series with a literature survey describes that the skin and tissue injuries are potential triggers responsible for the onset of BP in dialysis patients and that the incidence of BP in these patients seems to be much higher than that in the general population.

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Exercise Parameters Predict Technique Survival in Patients on Peritoneal Dialysis.

Takashin Nakayama, Kiyotaka Uchiyama, Naoki Washida, Kohkichi Morimoto, Kaori Muraoka, Keika Adachi, Takahiro Kasai, Kazutoshi Miyashita, Shu Wakino, Hiroshi Itoh

Blood purification 50 ( 3 ) 380 - 389 2021

ISSN 02535068

OBJECTIVE: The incremental shuttle walking test (ISWT) is an important marker of aerobic capacity in patients on peritoneal dialysis (PD). This study aimed to evaluate its predictive value for PD-related outcomes. METHODS: This single-center cohort study recruited outpatients on maintenance PD from our hospital between March 2017 and March 2018. Exercise capacity was assessed using measurement of ISWT and handgrip and quadriceps strength. Patients were divided into 2 groups according to the median of exercise capacity and prospectively followed up until cessation of PD, death, or the study end (October 2019). The primary end point of this study was technique survival rate, and secondary outcomes were rates of peritonitis-free survival and PD-related hospitalization-free survival. RESULTS: Among the 50 participants, age and PD vintage were [median (IQR)] 62.5 (58.3-70) and 3.5 (1.3-6.5) years, respectively. At the end of the study, 3 of the 28 participants (11%) in the long-ISWT group and 13 of the 22 participants (59%) in the short-ISWT group were transferred to hemodialysis. The short-ISWT group showed lower technique survival rate (p < 0.001), peritonitis-free survival rate (p = 0.01), and PD-related hospitalization-free survival rate (p < 0.01) than the long-ISWT group, whereas those survival rates did not differ when participants were divided by handgrip or quadriceps strength. Multivariate analysis revealed lower ISWT to be independently associated with technique failure (p = 0.002). CONCLUSION: The ISWT is an important predictor of technique survival for patients on PD. Monitoring and enhancing ISWT as a marker of aerobic capacity might improve PD-related outcomes.

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Mediastinal Cystic Parathyroid Adenoma Diagnosed by Somatostatin Receptor Scintigraphy

Yokota Kenichi, Kurihara Isao, Matsusaka Yohji, Emoto Katsura, Hishida Tomoyuki, Oshida Takuma, Kobayashi Sakiko, Murai-Takeda Ayano, Miyashita Kazutoshi, Matsuda Kohei, Nakagomi Takahiro, Matsuda Kosuke, Itoh Hiroshi

Internal Medicine (The Japanese Society of Internal Medicine) 60 ( 10 ) 1555 - 1560 2021

ISSN 09182918

<p>A 71-year-old man complained of nausea and loss of appetite for eight months prior to admission. He was transported to a hospital with disorientation and diagnosed with primary hyperparathyroidism by laboratory examinations. However, ultrasonography, computed tomography, and technetium-99m labeled methoxyisobutyl isonitrile (<sup>99m</sup>Tc-MIBI) with single-photon emission computed tomography did not yield definite results. In contrast, somatostatin receptor scintigraphy successfully identified the lesion responsible for the over-secretion of parathyroid hormone within the middle mediastinum. The tumor was successfully resected by surgery, and a histopathological analysis confirmed the parathyroid adenoma nature of the tumor. </p>

Successful Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis-Associated Rapidly Progressive-Interstitial Lung Disease by Plasma Exchange: Two Case Reports.

Rina Takahashi, Tadashi Yoshida, Kohkichi Morimoto, Yasushi Kondo, Jun Kikuchi, Shuntaro Saito, Sho Ishigaki, Yuko Kaneko, Tsutomu Takeuchi, Hiroshi Itoh, Mototsugu Oya

Clinical medicine insights. Case reports 14 11795476211036322 - 11795476211036322 2021

ISSN 1179-5476

BACKGROUND: Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) are frequently accompanied by rapidly progressive-interstitial lung disease (RP-ILD). They are often refractory to intensive immunosuppressive therapy and have poor prognosis. CASE PRESENTATION: A 73-year-old woman presented with fever, cold symptoms, and skin eruption for a month. She also exhibited muscle weakness on upper extremities slightly. The titer of anti-MDA5 antibody was extremely high, and computed tomography showed ground glass opacity and reticular shadows in the lungs. She was diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD and treated with intensive immunosuppressive therapy. However, the titer of anti-MDA5 antibody did not decrease satisfactorily, and plasma exchange was alternatively initiated. The titer decreased remarkably, and she obtained disease remission. Similarly, a 63-year-old woman presented with stiffness of the neck and hands, fever and cough. She was also diagnosed as anti-MDA5 antibody-positive classical DM-associated RP-ILD, because she had skin eruptions, slight muscle weakness, an elevation in anti-MDA5 antibody, and RP-ILD. She was unresponsive to intensive immunosuppressive therapy, but plasma exchange successfully improved the titer of anti-MDA5 antibody, the symptoms, and the findings of computed tomography. CONCLUSIONS: Although anti-MDA5 antibody-positive DM-associated RP-ILD has a high mortality rate, this report suggests the usefulness of plasma exchange to improve the prognosis.

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Effect of long-term amiodarone treatment on thyroid function in euthyroid Japanese patients: a 12-month retrospective analysis.

Kazutoshi Sugiyama, Sakiko Kobayashi, Isao Kurihara, Kazutoshi Miyashita, Kenichi Yokota, Takashi Kohno, Jaeduk Yoshimura Noh, Hiroshi Itoh

Endocrine journal 67 ( 12 ) 1247 - 1252 2020.12

ISSN 0918-8959

Amiodarone is an effective antiarrhythmic drug. However, it is associated with changes in thyroid function in euthyroid patients due to its high iodine content and intrinsic drug effects. Studies have been conducted in iodine-deficient and iodine-sufficient countries; however, data from countries with excessive iodine intake are lacking. Thus, this study aimed to evaluate the effect of long-term amiodarone treatment on thyroid function in euthyroid Japanese patients. Japanese adults aged ≥18 years who were treated with amiodarone for at least 90 consecutive days were included in this retrospective chart review. Patients with abnormal thyroid function test results at baseline were excluded. Serial changes in thyroid function tests at baseline and at days 30, 90, 180, 270, and 360 were analyzed using a mixed-effects model for repeated measures. In total, 46 patients with a mean age of 63.7 years were evaluated. The mean TSH level significantly increased from 1.62 μIU/mL at baseline to 3.43, 2.75, 2.84, 2.78, and 2.65 μIU/mL at days 30, 90, 180, 270, and 360, respectively. The mean free T4 level significantly increased from 1.3 ng/dL at baseline to 1.4, 1.5, 1.5, 1.5, and 1.5 ng/dL at days 30, 90, 180, 270, and 360, respectively. The mean free T3 level significantly decreased from 2.8 pg/mL at baseline to 2.4, 2.3, 2.3, 2.4, and 2.4 pg/mL at days 30, 90, 180, 270, and 360, respectively. In conclusion, significant changes in thyroid function persisted not only in the acute phase but also in the chronic phase of long-term amiodarone treatment.

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Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians

Kenya Honda, Yuko Sato, Koji Atarashi, Damian Plichta, Yasumichi Arai, Satoshi Sasajima, Sean Kearney, Wataru Suda, Kozue Takeshita, Takahiro Sasaki, Shoki Okamoto, Ashwin Skelly, Yuki Okamura, Hera Vlamakis, Youxian Li, Takeshi Tanoue, Hajime Takei, Hiroshi Nittono, Seiko Narushima, Junichiro Irie, Hiroshi Itoh, Kyoji Moriya, Yuki Sugiura, Makoto Suematsu, Nobuko Moritoki, Shinsuke Shibata, Dan Littman, Michael Fischbach, Masahira Hattori, Tsuyoshi Murai, Ramnik Xavier, Nobuyoshi Hirose

(Research Square Platform LLC) 2020.12

<title>Abstract</title>
Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified <italic>Parabacteroides merdae</italic> and <italic>Odoribacteraceae</italic> strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of <italic>P. merdae</italic> to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including <italic>Clostridioides difficile</italic> and vancomycin-resistant <italic>Enterococcus faecium</italic>. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.

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Effects of exercise on residual renal function in patients undergoing peritoneal dialysis: A post-hoc analysis of a randomized controlled trial.

Kiyotaka Uchiyama, Naoki Washida, Kohkichi Morimoto, Kaori Muraoka, Takashin Nakayama, Keika Adachi, Takahiro Kasai, Kazutoshi Miyashita, Shu Wakino, Hiroshi Itoh

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 24 ( 6 ) 668 - 676 2020.12

ISSN 1744-9979

We aimed to investigate the effects of exercise on renal outcomes in patients undergoing peritoneal dialysis (PD). In a post-hoc analysis of a randomized controlled trial of a 12-week home-based exercise program involving 47 patients undergoing PD, we excluded 18 patients with anuria and analyzed 13 and 16 patients in the usual care and exercise groups, respectively. The primary outcomes were weekly renal creatinine clearance (CCr) and urinary biomarkers: liver-type fatty acid-binding protein (L-FABP) and the microalbumin-to-creatinine ratio (ACR). Although the maintenance of weekly renal CCr in the exercise group was not significantly different compared with that in the usual care group (P = .09), urinary L-FABP levels (P = .02) and ACR (P = .04) were significantly decreased in the exercise group. To the best of our knowledge, this is the first study to demonstrate the beneficial effects of exercise on renal outcomes in patients undergoing PD.

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アルドステロン産生副腎腫瘍に対する腹腔鏡下副腎部分切除術の治療成績と高難易度症例の予測

武田利和, 安水洋太, 田中伸之, 松本一宏, 森田伸也, 小坂威雄, 水野隆一, 伊東伸剛, 栗原勲, 中塚誠之, 浅沼宏, 伊藤裕, 大家基嗣

日本泌尿器科学会総会 ((一社)日本泌尿器科学会総会事務局) 108回 810 - 810 2020.12

超高齢での褐色細胞腫摘出により糖尿病が寛解した1例

上妻嵩英, 栗原勲, 小林佐紀子, 横田健一, 宮下和季, 武田利和, 大家基嗣, 亀山香織, 伊藤裕

日本内科学会関東地方会 (日本内科学会-関東地方会) 664回 37 - 37 2020.11

Calcified cerebral embolism due to aortic valve calcification.

Takashin Nakayama, Shu Wakino, Hiroshi Itoh

Clinical and experimental nephrology 24 ( 11 ) 1084 - 1085 2020.11

ISSN 1342-1751

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JSH Statement: Tokyo declaration promoting salt reduction by the Japanese Society of Hypertension-the JSH Tokyo declaration.

Takuya Tsuchihashi, Toshihiko Ishimitsu, Katsuyuki Ando, Miho Kusaka, Atsuhiro Ichihara, Katsuyuki Miura, Yuhei Kawano, Takafumi Ishida, Hiroo Kumagai, Atsushi Sakima, Hiroyuki Takase, Hitomi Hayabuchi, Hiroshi Itoh

Hypertension research : official journal of the Japanese Society of Hypertension 43 ( 11 ) 1133 - 1134 2020.11

ISSN 0916-9636

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Proton pump inhibitors may hinder hypophosphatemic effect of lanthanum carbonate, but not of ferric citrate hydrate or sucroferric oxyhydroxide, in hemodialysis patients.

Hitoshi Minakuchi, Tadashi Yoshida, Noriko Kaburagi, Teppei Fujino, Sho Endo, Tomoko Yamashita Takemitsu, Norimasa Yamashita, Hiroshi Itoh, Mototsugu Oya

Renal failure 42 ( 1 ) 799 - 806 2020.11

ISSN 0886-022X

Because end-stage renal disease patients undergoing hemodialysis frequently take acid suppressants for the treatment or prevention of gastrointestinal diseases, it is important to clarify the drug-interactions between acid suppressants and phosphate binders on the control of serum phosphate levels. In the present study, we examined whether the phosphate-lowering effects of three phosphate binders, lanthanum carbonate (LC), ferric citrate hydrate (FCH), and sucroferric oxyhydroxide (SFOH), were affected by proton pump inhibitors (PPIs) in maintenance hemodialysis patients. Laboratory data for 71 patients who had been newly prescribed one of the three phosphate binders were examined. LC at a dosage of 500 ± 217 mg/day significantly decreased serum phosphate levels by -18% in the absence of a PPI (n = 9), while a dosage of 700 ± 230 mg/day only decreased it by -3% in the presence of a PPI (n = 10). Thus, the efficacy of LC in reducing serum phosphate levels was significantly hindered by the presence of PPIs. FCH significantly decreased serum phosphate levels by -18% in the absence of a PPI (n = 7, FCH: 571 ± 189 mg/day) and by -17% in the presence of a PPI (n = 20, FCH: 638 ± 151 mg/day). The decrease in serum phosphate levels by SFOH (393 ± 197 mg/day) was -7% in the absence of a PPI (n = 7), and SFOH at a dosage of 556 ± 316 mg/day significantly decreased serum phosphate levels by -13% in the presence of a PPI (n = 18). These results suggest that the phosphate-lowering effect of LC, but not of FCH or SFOH, is diminished in the presence of PPIs in hemodialysis patients.

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Conformational equilibrium shift underlies altered K(+) channel gating as revealed by NMR.

Iwahashi Y, Toyama Y, Imai S, Itoh H, Osawa M, Inoue M, Shimada I

Nature communications 11 ( 1 ) 5168 2020.10

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The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial.

Hitoshi Minakuchi, Shu Wakino, Hidenori Urai, Arata Kurokochi, Kazuhiro Hasegawa, Takeshi Kanda, Hirobumi Tokuyama, Hiroshi Itoh

Scientific reports 10 ( 1 ) 16626 - 16626 2020.10

The progression of chronic kidney disease (CKD) cannot be completely inhibited. We first explored factors contributing to CKD progression in patients with CKD in a prospective observational study. In the next phase, we focused on the effects of aldosterone, conducting a single-blinded placebo-controlled study using the selective mineralocorticoid receptor antagonist (MRA), eplerenone (25 mg/day). We recruited patients with CKD stage 2 and 3 whose plasma aldosterone concentration was above 15 ng/dL based on the prior data of a prospective observational study. In the CKD cohort study (n = 141), baseline plasma aldosterone concentration was identified as an independent contributory factor for the future rate of change in estimated glomerular filtration rate (eGFR). When the cut-off value for aldosterone was set at 14.5 ng/dL, the decline rate was significantly higher in patients with higher plasma aldosterone concentration (- 1.22 ± 0.39 ml/min/1.73 m2/year vs. 0.39 ± 0.40 ml/min/1.73 m2/year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone.

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Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19.

Shigeru Shibata, Hisatomi Arima, Kei Asayama, Satoshi Hoshide, Atsuhiro Ichihara, Toshihiko Ishimitsu, Kazuomi Kario, Takuya Kishi, Masaki Mogi, Akira Nishiyama, Mitsuru Ohishi, Takayoshi Ohkubo, Kouichi Tamura, Masami Tanaka, Eiichiro Yamamoto, Koichi Yamamoto, Hiroshi Itoh

Hypertension research : official journal of the Japanese Society of Hypertension 43 ( 10 ) 1028 - 1046 2020.10

ISSN 0916-9636

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than seven million people worldwide, contributing to 0.4 million deaths as of June 2020. The fact that the virus uses angiotensin-converting enzyme (ACE)-2 as the cell entry receptor and that hypertension as well as cardiovascular disorders frequently coexist with COVID-19 have generated considerable discussion on the management of patients with hypertension. In addition, the COVID-19 pandemic necessitates the development of and adaptation to a "New Normal" lifestyle, which will have a profound impact not only on communicable diseases but also on noncommunicable diseases, including hypertension. Summarizing what is known and what requires further investigation in this field may help to address the challenges we face. In the present review, we critically evaluate the existing evidence for the epidemiological association between COVID-19 and hypertension. We also summarize the current knowledge regarding the pathophysiology of SARS-CoV-2 infection with an emphasis on ACE2, the cardiovascular system, and the kidney. Finally, we review evidence on the use of antihypertensive medication, namely, ACE inhibitors and angiotensin receptor blockers, in patients with COVID-19.

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抗MDA5抗体陽性皮膚筋炎に血漿交換が奏功した一例

高橋利奈, 水口斉, 吉田理, 伊藤裕, 大家基嗣

日本透析医学会雑誌 ((一社)日本透析医学会) 53 ( Suppl.1 ) 543 - 543 2020.10

ISSN 1340-3451

落葉状天疱瘡と水疱性類天疱瘡の合併症例に対し血漿交換が奏功した一例

高橋利奈, 水口斉, 吉田理, 伊藤裕, 大家基嗣

日本透析医学会雑誌 ((一社)日本透析医学会) 53 ( Suppl.1 ) 544 - 544 2020.10

ISSN 1340-3451

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