研究者詳細 - 伊藤　裕

論文 - 伊藤　裕

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Host metabolic benefits of prebiotic exopolysaccharides produced by Leuconostoc mesenteroides

Miyamoto J., Shimizu H., Hisa K., Matsuzaki C., Inuki S., Ando Y., Nishida A., Izumi A., Yamano M., Ushiroda C., Irie J., Katayama T., Ohno H., Itoh H., Yamamoto K., Kimura I.

Gut Microbes （Taylor & Francis） 15 （ 1 ） 2161271 - 2161271 2023年

ISSN 19490976

Fermented foods demonstrate remarkable health benefits owing to probiotic bacteria or microproducts produced via bacterial fermentation. Fermented foods are produced by the fermentative action of several lactic acid bacteria, including Leuconostoc mesenteroides; however, the exact mechanism of action of these foods remains unclear. Here, we observed that prebiotics associated with L. mesenteroides-produced exopolysaccharides (EPS) demonstrate substantial host metabolic benefits. L. mesenteroides-produced EPS is an indigestible α-glucan, and intake of the purified form of EPS improved glucose metabolism and energy homeostasis through EPS-derived gut microbial short-chain fatty acids, and changed gut microbial composition. Our findings reveal an important mechanism that accounts for the effects of diet, prebiotics, and probiotics on energy homeostasis and suggests an approach for preventing lifestyle-related diseases by targeting bacterial EPS.

Risk factors of neonatal hypoglycemia in neonates born to mothers with gestational diabetes

Arimitsu T., Kasuga Y., Ikenoue S., Saisho Y., Hida M., Yoshino J., Itoh H., Tanaka M., Ochiai D.

Endocrine Journal （一般社団法人日本内分泌学会） 70 （ 5 ） 511 - 517 2023年

ISSN 09188959

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.

Impact of coronavirus disease 2019 in seasonal variation of hemoglobin A1c in adults with type 1 diabetes and the effect of the mode of treatment: a single-center retrospective study for 2019 and 2021 and analysis by the mode of treatment

Tanaka K., Meguro S., Itoh A., Kodani N., Itoh H.

Endocrine Journal （一般社団法人日本内分泌学会） 70 （ 8 ） 787 - 795 2023年

ISSN 09188959

The study was aimed to investigate the seasonal variation of hemoglobin A1c (HbA1c) in adults with type 1 diabetes (T1D) and the impact of coronavirus disease 2019 (COVID-19) by comparing 2019 and 2021 data and differences in treatment modes. This was a single-center retrospective observational study including 52 adult patients with T1D who regularly visited hospital in 2019 and 2021. Twenty-five patients used multiple daily injections (MDI)/self-measurement of blood glucose (SMBG), 16 used MDI/intermittently scanned continuous glucose monitoring (isCGM), 9 used sensor-augmented pump (SAP), and 2 used continuous subcutaneous insulin infusion (CSII)/isCGM. The mean HbA1c level was calculated for each month. The correlation between monthly means of temperature and HbA1c was investigated. Similar analyses were performed for the MDI/SMBG, MDI/isCGM, and SAP + CSII/isCGM groups. HbA1c levels in 2019 decreased in summer and increased in winter and showed a significant negative correlation with temperature (r = –0.652, p = 0.022). However, HbA1c in 2021 showed no seasonal variation and no correlation with temperature (r = –0.134, p = 0.678) and tended to decline after the three emergency declarations. HbA1c in the MDI/SMBG group showed the same trend as the whole group in 2019 and 2021. However, the effect of seasonal variation in HbA1c was lower in the MDI/isCGM group and the lowest in the SAP + CSII/isCGM group in 2019. The impact of emergency declaration on HbA1c level was small for the MDI/isCGM group and smaller for the SAP + CSII/isCGM group in 2021. The COVID-19 pandemic has affected the seasonal variation of HbA1c levels in T1D; the variation differed according to the treatment mode.

The body mass index change is associated with death or hemodialysis transfer in Japanese patients initiating peritoneal dialysis

Kojima D., Washida N., Uchiyama K., Hama E.Y., Nagasaka T., Kusahana E., Nakayama T., Nagashima K., Sato Y., Morimoto K., Kanda T., Itoh H.

Renal Failure 45 （ 1 ） 2163904 - 2163904 2023年

ISSN 0886022X

A decreased body mass index (BMI) over time is associated with a poor prognosis for patients on hemodialysis. We aimed to examine whether this association also applies to patients with peritoneal dialysis (PD). BMI change was defined as the percentage change in the BMI between the time of PD catheter insertion and six months after its insertion. The association between the BMI change and all-cause mortality or PD discontinuation from six months after PD catheter insertion until October 2021 was investigated. This retrospective cohort study included 122 patients (aged 61.1 ± 12.1 years; 90 males) who underwent PD catheter insertion between January 2008 and March 2020. The median follow-up period was 43.1 (21.2–78.8) months. The median six-month percentage change in the BMI was −2.14 (−5.56–1.84)%, and patients were categorized into tertiles based on their BMI changes. The fully-adjusted Cox regression analysis revealed a significantly higher rate of PD discontinuation or all-cause mortality (hazard ratio (HR): 2.48; 95%; confidence interval (CI): 1.41–4.37) in patients with the lowest tertile (T1, BMI change: < −4.13%) compared to patients with the middle tertile (T2, BMI change: −4.13%–0.67%). The risk was not significantly higher in patients with the highest tertile (T3, BMI change: >0.67%) than those in the T2 group (HR: 1.18; 95% CI: 0.66–2.11). A decreased BMI over time is independently associated with HD transfer or all-cause mortality among patients initiating PD, which highlights the importance of the 6-month BMI change as a novel prognostic marker.

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ASO Author Reflections: Epidural Analgesia Decreases In-Hospital Mortality, Respiratory Complications, and Anastomotic Leakage After Minimally Invasive Esophagectomy for Esophageal Cancer

Hirano, Y; Kaneko, H; Konishi, T; Itoh, H; Matsuda, S; Kawakubo, H; Daiko, H; Itano, O; Yasunaga, H; Kitagawa, Y

ANNALS OF SURGICAL ONCOLOGY 29 （ 13 ） 8235 - 8236 2022年12月

ISSN 1068-9265

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Effect of Tolvaptan in Patients with Chronic Kidney Disease Stage G5, and Impact of Concomitant Use of Thiazide Diuretics: A Retrospective Cohort Study

Uchiyama K., Kojima D., Hama E.Y., Nagasaka T., Nakayama T., Takahashi R., Tajima T., Morimoto K., Washida N., Itoh H.

Drugs - Real World Outcomes 9 （ 4 ） 649 - 657 2022年12月

ISSN 21991154

Background: The diuretic effect of tolvaptan, a vasopressin V2 receptor antagonist, in patients with severe renal dysfunction remains poorly characterized. Thiazide diuretics reduce urinary volume (UV) in patients with nephrogenic diabetes insipidus, which lacks V2 receptor function. Objective: This retrospective study investigated the acute urinary effects of tolvaptan in patients with stage G5 chronic kidney disease and congestive heart failure (CHF), and the impact of thiazide diuretics on the urinary effects of tolvaptan. Methods: UVs 24 h before and after tolvaptan administration and 30-day dialysis initiation rate were compared between patients with and without thiazide diuretic administration. Results: Thiazide diuretics were used in 26 of the 106 recruited patients (age 73.4 ± 13.0 years; estimated glomerular filtration rate 8.07 ± 3.13 mL/min/1.73 m2). The pre- and post-tolvaptan 24-h UVs were significantly higher in patients not administered thiazide diuretics (1043.4 ± 645.6 vs. 1422.2 ± 774.0 mL/day; p < 0.001) than in those administered thiazide diuretics (1177.3 ± 686.5 vs. 1173.1 ± 629.1 mL/day; p = 0.93). In a multivariate regression model, thiazide diuretic use was significantly associated with decreased 24-h UV (β coefficient − 486.7, 95% confidence interval [CI] − 674.5 to − 298.8); increased urine osmolality (β coefficient 37.7, 95% CI 17.1–58.4); increased body weight (β coefficient 0.62, 95% CI 0.31–0.92); and increased 30-day dialysis initiation rate (odds ratio 3.40, 95% CI 1.18–9.82) after tolvaptan administration. Conclusions: Tolvaptan exhibited significant diuretic effects in patients with CHF, including those with severe renal dysfunction, which were diminished with concomitant thiazide diuretic use.

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Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study

Inaishi J., Saisho Y., Watanabe Y., Tsuchiya T., Sasaki H., Masaoka T., Itoh H.

BMC Endocrine Disorders 22 （ 1 ） 20 - 20 2022年12月

Background: We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking. Methods: Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching. Results: HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05). Conclusions: Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW. Trial registration: Clinical trial registry number; UMIN000016390 and jRCTs031180320. Approval date of Registry and the Registration: December 12, 2014.

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ASO Visual Abstract: Short-Term Outcomes of Epidural Analgesia in Minimally Invasive Esophagectomy for Esophageal Cancer: Nationwide Inpatient Data Study in Japan

Hirano, Y; Kaneko, H; Konishi, T; Itoh, H; Matsuda, S; Kawakubo, H; Uda, K; Matsui, H; Fushimi, K; Daiko, H; Itano, O; Yasunaga, H; Kitagawa, Y

ANNALS OF SURGICAL ONCOLOGY 29 （ 13 ） 8237 - 8238 2022年12月

ISSN 1068-9265

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High body mass index is a risk factor for transition to hemodialysis or hybrid therapy and peritoneal dialysis-related infection in Japanese patients undergoing peritoneal dialysis

Hama E.Y., Uchiyama K., Nagasaka T., Kusahana E., Nakayama T., Yasuda I., Morimoto K., Washida N., Itoh H.

International Urology and Nephrology 54 （ 12 ） 3193 - 3202 2022年12月

ISSN 03011623

Purpose: Obesity may negatively impact the clinical outcomes of patients undergoing peritoneal dialysis (PD). However, the impact of obesity on PD-related outcomes remains unclear. We herein examined the association of high body mass index (BMI) with complete hemodialysis (HD) transfer, transition to HD and PD/HD hybrid therapy, peritonitis, catheter exit-site and tunnel infection (ESI/TI), and heart failure-related hospitalization. Methods: This retrospective cohort study included 120 patients who underwent PD-catheter insertion between January 2008 and June 2018. BMI ≥ 25 kg/m2 at the time of PD-catheter insertion was defined as high BMI, and its association with outcomes was analyzed using the log-rank test and Cox proportional hazards models. Results: The follow-up duration was 46.2 (23.3–75.3) months. The time until transfer to HD and hybrid therapy was significantly shorter in the high BMI group than that in the low BMI group, whereas the time until HD transfer was not significantly different between the two groups (P < 0.001 and 0.18, respectively). Peritonitis-free and ESI/TI-free survivals were significantly shorter in the high BMI group than those in the low BMI group (P = 0.006 and 0.03, respectively). After adjusting for age, sex, diabetes mellitus, and estimated glomerular filtration rate, high BMI remained a significant risk factor for transferring to HD and hybrid therapy, peritonitis, and ESI/TI (hazard ratio [HR] 2.60, P < 0.001; HR 2.08, P = 0.01; HR 2.64, P = 0.02, respectively). Conclusion: BMI ≥ 25 kg/m2 is a risk factor for transition to HD and hybrid therapy, peritonitis, and ESI/TI, but not for complete HD transfer in Japanese patients with PD.

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Iliopsoas abscess in patients receiving hemodialysis: a case series and a literature survey

Oshida T., Yoshida T., Itoh H., Oya M.

Renal Replacement Therapy 8 （ 1 ） 2022年12月

Background: Iliopsoas abscess is a relatively rare but serious infectious disease. Infectious disease is one of the major causes of death among patients receiving hemodialysis for end-stage renal disease (ESRD). Case presentation: We experienced three cases of iliopsoas abscess in patients receiving hemodialysis. The infection route was distinct in each case. A 79-year-old woman with ESRD due to autosomal dominant polycystic kidney disease exhibited bilateral iliopsoas abscesses caused by bacterial contamination during a lumbar epidural block procedure. A 60-year-old woman with ESRD due to diabetic nephropathy was diagnosed as having an iliopsoas abscess, caused by the direct invasion of bacteria from a renal abscess. A 78-year-old woman who started hemodialysis because of nephrosclerosis developed an iliopsoas abscess caused by the hematogenous spread of bacteria from emphysematous cystitis. All three cases were treated with antibiotics and/or percutaneous drainage. A survey of published reports suggested that iliopsoas abscess can be caused by infection through a variety of routes in hemodialysis patients. Conclusion: Because hemodialysis patients are at a high risk of infection because of their immunocompromised state, physicians should pay close attention to infection prevention. If iliopsoas abscess is suspected, examinations such as computed tomography, magnetic resonance imaging, and blood culture sampling should be conducted promptly, followed by appropriate treatment with antibiotics and/or drainage.

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The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease

Takahashi R., Kanda T., Komatsu M., Itoh T., Minakuchi H., Urai H., Kuroita T., Shigaki S., Tsukamoto T., Higuchi N., Ikeda M., Yamanaka R., Yoshimura N., Ono T., Yukioka H., Hasegawa K., Tokuyama H., Wakino S., Itoh H.

Scientific Reports 12 （ 1 ） 6398 - 6398 2022年12月

ISSN 2045-2322

Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear. We generated NNMT-deficient mice and a unilateral ureter obstruction (UUO) model and conducted two clinical studies on human CKD to investigate the role of NNMT in CKD and fibrosis. In UUO, renal NNMT expression and the degraded metabolites of NAM increased, while NAD + and NAD + precursors decreased. NNMT deficiency ameliorated renal fibrosis; mechanistically, it (1) increased the DNA methylation of connective tissue growth factor (CTGF), and (2) improved renal inflammation by increasing renal NAD + and Sirt1 and decreasing NF-κB acetylation. In humans, along with CKD progression, a trend toward a decrease in serum NAD + precursors was observed, while the final NAD + metabolites were accumulated, and the level of eGFR was an independent variable for serum NAM. In addition, NNMT was highly expressed in fibrotic areas of human kidney tissues. In conclusion, increased renal NNMT expression induces NAD + and methionine metabolism perturbation and contributes to renal fibrosis.

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Vaccination against connective tissue growth factor attenuates the development of renal fibrosis

Nakayama T., Azegami T., Hayashi K., Hishikawa A., Yoshimoto N., Nakamichi R., Sugita E., Itoh H.

Scientific Reports 12 （ 1 ） 10933 - 10933 2022年12月

ISSN 2045-2322

There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin–creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.

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Effects of a remote patient monitoring system for patients on automated peritoneal dialysis: a randomized crossover controlled trial

Uchiyama K., Morimoto K., Washida N., Kusahana E., Nakayama T., Itoh T., Kasai T., Wakino S., Itoh H.

International Urology and Nephrology 54 （ 10 ） 2673 - 2681 2022年10月

ISSN 03011623

Purpose: Remote patient monitoring (RPM) has contributed to improved patient-centered outcomes and prognosis in patients with end-stage renal disease on automated peritoneal dialysis (APD). However, evidence from prospective trials is lacking. Methods: The participants (n = 15; median age: 65 years; males: 10; peritoneal dialysis vintage: 6.4 ± 3.5 years) randomly received APD therapy using the Kaguya® APD system either with or without the connective use of the cloud-based RPM software Sharesource® for 12 weeks. The primary outcome was patient satisfaction assessed using a modified nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) questionnaire. The secondary outcomes were healthcare resource consumption, the health-related quality of life (HRQOL) subscales assessed with the Kidney Disease Quality of Life-Short Form questionnaire, and clinical laboratory parameters. Results: Significant improvements were observed in the TSQM-9 subscales of Effectiveness (64.4 ± 18.8 vs. 57.8 ± 18.8; P = 0.006) and Convenience (76.3 ± 15.4 vs. 63.3 ± 17.3; P < 0.001) in patients on Sharesource®. Moreover, Sharesource® reduced the total amount of healthcare resource consumption (0.80 ± 1.32 vs. 1.87 ± 2.39 times/12 weeks; P = 0.02) and consultation time during regular monthly visits (813 ± 269 vs. 1024 ± 292 s; P < 0.001). A significant increase in ultrafiltration volume was found associated with more frequent modification of APD prescription in patients with Sharesource®. Sharesource® also improved the HRQOL subscale of General Health and Vitality. Conclusion: Sharesource® can improve patient-centered outcomes in patients on APD while reducing the treatment burden for both patients and medical staff. Trial registration: The study was registered in the Japan Registry of Clinical Trials (jRCT Number: jRCTs032190005).

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Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage

Ida-Naitoh M., Tokuyama H., Futatsugi K., Yasuda M., Adachi K., Kanda T., Tanabe Y., Wakino S., Itoh H.

Kidney International 102 （ 4 ） 798 - 814 2022年10月

ISSN 00852538

The small GTPase protein RhoA has two effectors, ROCK (Rho-associated protein kinase 1) and mDIA1 (protein diaphanous homolog 1), which cooperate reciprocally. However, temporal regulation of RhoA and its effectors in obesity-induced kidney damage remains unclear. Here, we investigated the role of RhoA activation in the proximal tubules at the early and late stages of obesity-induced kidney damage. In mice, a three-week high-fat–diet induced proximal tubule hypertrophy and damage without increased albuminuria, and RhoA/mDIA1 activation without ROCK activation. Conversely, a 12-week high-fat diet induced proximal tubule hypertrophy, proximal tubule damage, increased albuminuria, and RhoA/ROCK activation without mDIA1 elevation. Proximal tubule hypertrophy resulting from cell cycle arrest accompanied by downregulation of the multifunctional cyclin-dependent kinase inhibitor p27Kip1 was elicited by RhoA activation. Mice overexpressing proximal tubule-specific and dominant-negative RHOA display amelioration of high-fat diet-induced kidney hypertrophy, cell cycle abnormalities, inflammation, and renal impairment. In human proximal tubule cells, mechanical stretch mimicking hypertrophy activated ROCK, which triggered inflammation. In human kidney samples from normal individuals with a body mass index of about 25, proximal tubule cell size correlated with body mass index, proximal tubule cell damages, and mDIA1 expression. Thus, RhoA activation in proximal tubules is critical for the initiation and progression of obesity-induced kidney damage. Hence, the switch in the downstream RhoA effector in proximal tubule represents a transition from normal to pathogenic kidney adaptation and to body weight gain, leading to obesity-induced kidney damage.

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Association of cardiovascular disease risk and changes in renin levels by mineralocorticoid receptor antagonists in patients with primary aldosteronism

Nomura M., Kurihara I., Itoh H., Ichijo T., Katabami T., Tsuiki M., Wada N., Yoneda T., Sone M., Oki K., Yamada T., Kobayashi H., Tamura K., Ogawa Y., Inagaki N., Yamamoto K., Otsuki M., Yabe D., Izawa S., Takahashi Y., Suzuki T., Yasoda A., Tanabe A., Naruse M., Fukuda H., Tanaka Y., Takeda Y., Umakoshi H., Shibayama Y., Yoshimoto T., Kawashima J., Takahashi K., Fujita M., Watanabe M., Matsuda Y., Shibata H., Kamemura K., Fujii Y., Rakugi H., Ogo A., Okamura S., Miyauchi S., Yanase T., Kawamura T., Fukuoka T., Kai T., Yoshikawa Y., Hashimoto S., Yamada M., Sakamoto R., Yoshiro C.

Hypertension Research 45 （ 9 ） 1476 - 1485 2022年09月

ISSN 09169636

A recent report stated that patients with primary aldosteronism who remain renin suppressed during mineralocorticoid receptor antagonist treatment might have a higher risk of developing cardiovascular disease than those with unsuppressed renin activity. We retrospectively investigated the incidence of composite cardiovascular disease and risk factors for cardiovascular disease in 1115 Japanese patients with primary aldosteronism treated with mineralocorticoid receptor antagonists. The median follow-up period was 3.0 years, and the incidence of cardiovascular events was very low (2.1%) throughout 5 years of follow-up. Changes in plasma renin activity from before to after mineralocorticoid receptor antagonist treatment were divided into three groups based on tertile, low, intermediate, and high plasma renin activity change groups, with incidences of cardiovascular disease events of 2.1%, 0.5%, and 3.7%, respectively. Multivariate Cox regression analysis revealed age (adjusted hazard ratio, 1.07; 95% confidence interval, [1.02–1.12]) and body mass index (adjusted hazard ratio, 1.13 [1.04–1.23]) as independent risk factors for cardiovascular disease. The high plasma renin activity change group had significantly higher cardiovascular disease risk with mineralocorticoid receptor antagonist treatment than the intermediate plasma renin activity change group (adjusted hazard ratio, 5.71 [1.28–25.5]). These data suggest that a high change in renin level after mineralocorticoid receptor antagonist treatment may not necessarily predict a better prognosis of cardiovascular disease in patients with primary aldosteronism.

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Virtual management of hypertension: Lessons from the COVID-19 pandemic-International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension

Khan N.A., Stergiou G.S., Omboni S., Kario K., Renna N., Chapman N., McManus R.J., Williams B., Parati G., Konradi A., Islam S.M., Itoh H., Mooi C.S., Green B.B., Cho M.C., Tomaszewski M.

Journal of Hypertension 40 （ 8 ） 1435 - 1448 2022年08月

ISSN 02636352

The coronavirus disease 2019 pandemic caused an unprecedented shift from in person care to delivering healthcare remotely. To limit infectious spread, patients and providers rapidly adopted distant evaluation with online or telephone-based diagnosis and management of hypertension.It is likely that virtual care of chronic diseases including hypertension will continue in some form into the future. The purpose of the International Society of Hypertension's (ISH) position paper is to provide practical guidance on the virtual management of hypertension to improve its diagnosis and blood pressure control based on the currently available evidence and international experts' opinion for nonpregnant adults. Virtual care represents the provision of healthcare services at a distance with communication conducted between healthcare providers, healthcare users and their circle of care. This statement provides consensus guidance on: selecting blood pressure monitoring devices, accurate home blood pressure assessments, delivering patient education virtually, health behavior modification, medication adjustment and long-term virtual monitoring. We further provide recommendations on modalities for the virtual assessment and management of hypertension across the spectrum of resource availability and patient ability.

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Late Dialysis Modality Education Could Negatively Predict Peritoneal Dialysis Selection

Nakayama T., Nishioka K., Uchiyama K., Morimoto K., Kusahana E., Washida N., Yamaguchi S., Azegami T., Yoshida T., Itoh H.

Journal of Clinical Medicine 11 （ 14 ） 2022年07月

ISSN 2077-0383

Patients with end-stage renal disease are less likely to choose peritoneal dialysis (PD) as renal replacement therapy (RRT). The reasons for this biased selection are still poorly understood. In this study, we evaluated the effect of the timing of RRT education on PD selection. This single-center retrospective observational study included patients who initiated maintenance dialysis at our hospital between April 2014 and July 2021. A logistic regression analysis was performed to investigate the association of RRT education timing with PD selection. Among the 355 participants (median age [IQR] 70 (59–79) years; 28.7% female), 53 patients (14.9%) and 302 patients (85.1%) selected PD and hemodialysis, respectively. Multivariate analysis demonstrated that high estimated glomerular filtration (eGFR) at RRT education positively predicted PD selection (p < 0.05), whereas old age (p < 0.01) and high Charlson comorbidity index (p < 0.05) were negative predictors of PD selection. Female sex (p = 0.44), welfare public assistance (p = 0.78), living alone (p = 0.25), high geriatric nutritional risk index (p = 0.10) and high eGFR at first visit to the nephrology department (p = 0.83) were not significantly associated with PD selection. Late RRT education could increase the biased selection of dialysis modality.

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Prevalence of hypertensive diseases and treated hypertensive patients in Japan: A nationwide administrative claims database study

Waki T., Miura K., Tanaka-Mizuno S., Ohya Y., Node K., Itoh H., Rakugi H., Sato J., Goda K., Kitsuregawa M., Ishikawa T., Mitsutake N.

Hypertension Research 45 （ 7 ） 1123 - 1133 2022年07月

ISSN 09169636

We investigated the prevalence of hypertensive patients and treated hypertensive patients using a Japanese nationwide administrative claims database. We analyzed national database data from 2014, including all claims data, provided by the Ministry of Health, Labour and Welfare of Japan. Hypertensive diseases were identified using Japanese standardized disease codes. Among hypertensive patients, treated hypertensive patients were defined by the prescription of any antihypertensive medication, identified using national health insurance price listing codes. We calculated and compared the number and age-adjusted prevalence of hypertensive patients and treated hypertensive patients by prefecture and the proportion of these patients by the size of medical facilities. In 2014, approximately 27 million Japanese people were identified as hypertensive, among which 89.6% were treated. The age-adjusted prevalence of hypertensive patients (per 100,000 persons) among women and men was 21,414 and 21,084, respectively. The age-adjusted prevalence of treated hypertensive patients (per 100,000 persons) among women and men was 19,118 and 18,974, respectively. While the prevalence of hypertensive and treated hypertensive patients varied geographically, the prevalence remained similar between the sexes. Approximately 59% of hypertensive patients visited clinics (0 to 19 beds) in Japan. In Japan, 27 million people were diagnosed with hypertensive diseases, and approximately 90% of these patients were treated with any antihypertensive medication in 2014. The distribution of hypertensive patients varied geographically throughout Japan.

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Serum thymus and activation-regulated chemokine level is associated with the severity of chronic kidney disease-associated pruritus in patients undergoing peritoneal dialysis

Nakayama T., Morimoto K., Uchiyama K., Kusahana E., Washida N., Azegami T., Kanda T., Yoshida T., Itoh H.

Peritoneal Dialysis International 42 （ 4 ） 415 - 424 2022年07月

ISSN 08968608

Background: Thymus and activation-regulated chemokine (TARC), which induces a Th2-dominated inflammation, is a well-known biomarker that reflects the severity of atopic dermatitis. The present study aimed to evaluate TARC as a Th2-associated marker with chronic kidney disease-associated pruritus (CKD-aP) in patients with peritoneal dialysis (PD). Methods: This single-centre cross-sectional study included patients who underwent PD in our hospital between August 2020 and July 2021. The severity and impaired quality of life (QOL) of CKD-aP were assessed using the visual analogue scale (VAS) and Japanese version of the 5-D itch scale (5D-J), respectively. Results: A total of 48 patients with PD were included in the present study. Age and dialysis vintage were (mean ± SD) 64.8 ± 12.0 year and (median (IQR)) 38.5 (11.5–91.5) month, respectively. VAS and 5D-J scores were 3.3 ± 2.0 and 10.5 (9.0–12.0), respectively. Serum TARC level was 481.5 (278.9–603.4) pg/mL (upper limits of normal 450 pg/mL) and significantly correlated with VAS (r = 0.39, p = 0.006) and 5D-J score (r = 0.37, p = 0.009). Multivariate linear analysis revealed that higher serum TARC level was significantly associated with VAS (p < 0.001) and 5D-J score (p < 0.001). Furthermore, the serum brain natriuretic peptide level tended to be associated with VAS (p = 0.060) and 5D-J score (p = 0.029). Conclusion: Serum TARC level is an independent predictor of the severity and impaired QOL of CKD-aP in patients with PD, and TARC might be involved in the pathogenesis of CKD-aP.

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Serial measurement of B-type natriuretic peptide and future cardiovascular events in patients with type 2 diabetes mellitus without known cardiovascular disease

Ikeda S., Shinohara K., Enzan N., Matsushima S., Tohyama T., Funakoshi K., Kishimoto J., Itoh H., Komuro I., Tsutsui H.

International Journal of Cardiology 356 98 - 104 2022年06月

ISSN 01675273

Background: In patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients. Methods: We analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study. Results: Data from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5–29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low–low BNP group (baseline ≤35 pg/mL and 12-month ≤35 pg/mL), low–high BNP group as well as high–high BNP group was associated with cardiovascular events (HR: low–high, 2.05 [P = 0.004]; high–high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High–low BNP group tended to be associated with non-renal cardiovascular events (HR vs low–low: 2.05 [P = 0.056]). Conclusions: BNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

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