研究者詳細 - 和田　淳

論文 - 和田　淳

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Mesenchymal stem cells-derived extracellular vesicles as 'natural' drug delivery system for tissue regeneration 査読

Kenji Tsuji, Shinji Kitamura, Jun Wada

BIOCELL 46 ( 4 ) 899 - 902 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：TECH SCIENCE PRESS

Mesenchymal stem cells (MSCs) have abilities to mediate tissue protection through mechanisms of antiapoptosis, anti-oxidative stress and anti-fibrosis as well as tissue regeneration through mechanisms of cell proliferation, differentiation and angiogenesis. These effects by MSCs are mediated by a variety of factors, including growth factors, cytokines and extracellular vesicles (EVs). Among these factors, EVs, containing proteins, mRNA and microRNAs (miRNA), may carry their contents into distant tissues with high stability. Therefore, the treatment with MSC-derived EVs may be promising as 'natural' drug delivery systems (DDS). Especially, the treatment of MSCderived EVs with the manipulation of specific miRNAs expression has been reported to be beneficial under a variety of diseases and tissue injuries. The overexpression of specific miRNAs in the EVs might be through pre-loading method using the gene editing system by plasmid vector or post-loading method to load miRNA mimics into EVs by electroporation or calcium chloride-mediated transfection. Despite current several challenges for clinical use, it should open the next era of regenerative medicine for a variety of diseases. In this article, we highlight the therapeutic potential of MSC-derived EVs as 'natural' DDS and current challenges.

DOI： 10.32604/biocell.2022.018594

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Real-world data on vitamin D supplementation and its impacts in systemic lupus erythematosus: Cross-sectional analysis of a lupus registry of nationwide institutions (LUNA). 査読国際誌

Keigo Hayashi, Ken-Ei Sada, Yosuke Asano, Yu Katayama, Keiji Ohashi, Michiko Morishita, Yoshia Miyawaki, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Nobuyuki Yajima, Ryusuke Yoshimi, Yasuhiro Shimojima, Shigeru Ohno, Hiroshi Kajiyama, Kunihiro Ichinose, Shuzo Sato, Michio Fujiwara, Jun Wada

PloS one 17 ( 6 ) e0270569 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE. METHODS: A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control. RESULTS: Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups. CONCLUSIONS: Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed.

DOI： 10.1371/journal.pone.0270569

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Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism. 査読国際誌

Natsumi Uchiyama-Matsuoka, Kenji Tsuji, Haruhito A Uchida, Shinji Kitamura, Yoshihiko Itoh, Yuki Nishiyama, Eisaku Morimoto, Satoshi Fujisawa, Tomohiro Terasaka, Takayuki Hara, Kanako Ogura-Ochi, Kenichi Inagaki, Jun Wada

Frontiers in endocrinology 13 1048863 - 1048863 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: While it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism. METHODS: Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. RESULTS: Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average ΔeGFR of -41.1 mL/min/1.73 m2) and an increase in eGFR in hypothyroidism (an average ΔeGFR of 7.1 mL/min/1.73 m2). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for ΔeGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. CONCLUSIONS: We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism.

DOI： 10.3389/fendo.2022.1048863

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First-in-human autologous implantation of genetically modified adipocytes expressing LCAT for the treatment of familial LCAT deficiency

Jun Wada

Heliyon 2022年

The Beneficial Effect of Personalized Lifestyle Intervention in Chronic Kidney Disease Follow-Up Project for National Health Insurance Specific Health Checkup: A Five-Year Community-Based Cohort Study

Jun Wada

Medicina 2022年

THE MINIMALLY IMPORTANT DIFFERENCE AS THE INTERPRETABILITY OF EMOTIONAL HEALTH DOMAIN IN JAPANESE VERSION OF LUPUSPRO FOR SLE PATIENTS; PRELIMINARY RESULTS OF A PROSPECTIVE COHORT STUDY

Jun Wada

Annals of the Rheumatic Diseases 2022年

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice 査読

Jun Wada

Nature Aging 1 ( 12 ) 1117 - 1126 2021年12月

Semaporin3A inhibitor ameliorates renal fibrosis through the regulation of JNK signaling 査読

Yizhen Sang, Kenji Tsuji, Kazuhiko Fukushima, Kensaku Takahashi, Shinji Kitamura, Jun Wada

AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 321 ( 6 ) F740 - F756 2021年12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：AMER PHYSIOLOGICAL SOC

Renal fibrosis is the common pathological pathway in progressive renal diseases. In the present study, we analyzed the roles of semaphorin 3 A (SEMA3A) on renal fibrosis and the effect of SEMA3A inhibitor (SEMA3A-I) using a unilateral ureteral obstruction (UUO) mouse model. Expression of SEMA3A in the proximal tubulus and neuropilin-1, a recepor of SEMA3A, in fibloblast and tubular cells were increased in UUO kidneys. The expression of myofibroblast marker tenascin-C and fibronection as well as renal fibrosis were increased in UUO kidneys, all of which were ameliorated by SEMA3A-I. In addition, the JNK signaling pathway, known as the target of SEMA3A signaling, was activated in proximal tubular cells and fibroblast cells after UUO surgery, and SEMA3A-I significantly attenuated the activation. In vitro, treatments with SEMA3A as well as transforming growth factor-beta 1 (TGF-beta 1) in human proximal tubular cells lost epithelial cell characteristics, and SEMA3A-1 significantly ameliorated this transformation. The JNK inhibitor SP600125 partially reversed SEMA3A and TGF-beta 1-induced cell transformation, indicating that JNK signaling is involved in SEMA3A-induced renal fibrosis. In addition, treatment with SEMA3A in fibroblast cells activated expression of tenascin-C, collagen type I, and fibronection, indicating that SEMA3A may accelerate renal fibrosis through the activation of fibroblast cells. Analysis of human data revealed the positive correlation between urinary SEMA3A and urinary N-acetyl-beta-D-glucosaminidase, indicating the association between SEMA3A and tubular injury. In conclusion, SEMA3A signaling is involved in renal fibrosis through the JNK signaling pathway and SEMA3A-I might be a therapeutic option for protecting from renal fibrosis.NEW & NOTEWORTHY Renal fibrosis is the common pathological pathway in the progression of renal diseases. This study, using a unilateral ureteral obstruction (UUO) mouse model, indicated increased semaphorin3A (SEMA3A) signaling in renal tubular cells as well as fibroblast cells under UUO surgery, and SEMA3A inhibitor ameliorated UUO-induced renal fibrosis through the regulation of JNK signaling. The study proposes the potential therapeutic option of SEMA3A inhibitor to treat renal fibrosis.

DOI： 10.1152/ajprenal.00234.2021

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Presence of decoy cells for 6 months on urine cytology efficiently predicts BK virus nephropathy in renal transplant recipients 査読

Takanori Sekito, Motoo Araki, Kasumi Yoshinaga, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Tanabe, Hidemi Takeuchi, Hiroshi Morinaga, Masashi Kitagawa, Shinji Kitamura, Hitoshi Sugiyama, Jun Wada, Hiroyuki Yanai, Yasutomo Nasu

INTERNATIONAL JOURNAL OF UROLOGY 28 ( 12 ) 1240 - 1246 2021年12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：WILEY

Objectives To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation. Methods In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. Results In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve = 0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6 months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6 months (0/77; P = 0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%). Conclusions The detection of decoy cells at 6 months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy.

DOI： 10.1111/iju.14679

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Management of corticosteroid-dependent eosinophilic interstitial nephritis A case report 査読

Katsuyuki Tanabe, Natsumi Matsuoka-Uchiyama, Tomoyo Mifune, Chieko Kawakita, Hitoshi Sugiyama, Jun Wada

MEDICINE 100 ( 50 ) 2021年12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：LIPPINCOTT WILLIAMS & WILKINS

Introduction: Drug-induced acute interstitial nephritis (DI-AIN) is an important cause of acute kidney injury. In renal biopsy specimens, tubulitis with eosinophilic infiltration is suggestive of DI-AIN. Although corticosteroid therapy and discontinuation of the offending drug can improve renal dysfunction in most cases of DI-AIN, some patients experience AIN recurrence, leading to corticosteroid dependency. Corticosteroid-dependent eosinophilic interstitial nephritis presents a difficult dilemma in diagnosis and information regarding optimum management is limited. Patient concerns: A 25-year-old man, who received treatment with carbamazepine, zonisamide, valproate, and lacosamide for temporal lobe epilepsy, showed an increase in serum creatinine level from 0.98 to 1.29 mg/dL over a period of 6 months. Although he exhibited no symptoms, his serum creatinine level continued to increase to 1.74 mg/dL. Diagnosis: Renal biopsy revealed tubulitis and interstitial inflammatory infiltrates with eosinophils. Immunological and ophthalmological examinations showed no abnormal findings, and thus, his renal dysfunction was presumed to be caused by DI-AIN. Although oral prednisolone (PSL) administration (40 mg/d) and discontinuation of zonisamide immediately improved his renal function, AIN recurred 10 months later. The increase in PSL dose along with discontinuation of valproate and lacosamide improved renal function. However, 10 months later, recurrent AIN with eosinophilic infiltration was confirmed by further biopsy. The patient was therefore diagnosed with corticosteroid-dependent eosinophilic interstitial nephritis. Interventions: To prevent life-threatening epilepsy, carbamazepine could not be discontinued; hence, he was treated with an increased dose of PSL (60 mg/d) and 1500 mg/d of mycophenolate mofetil (MMF). Outcomes: MMF was well tolerated and PSL was successfully tapered to 5 mg/d; renal function stabilized over a 20-month period. Lessons: The presence of underdetermined autoimmune processes and difficulties in discontinuing the putative offending drug discontinuation are contributing factors to corticosteroid dependency in patients with eosinophilic interstitial nephritis. MMF may be beneficial in the management of corticosteroid-dependent eosinophilic interstitial nephritis by reducing the adverse effects related to high-dose and long-term corticosteroid use.

DOI： 10.1097/MD.0000000000028252

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Commentary on Intraglumerular dysfunction predicts kidney failure in the type 2 diabetes 査読

Jun Wada

JOURNAL OF DIABETES INVESTIGATION 12 ( 12 ) 2124 - 2125 2021年12月

Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database 査読

Hajime Nagasu, Yuichiro Yano, Hiroshi Kanegae, Hiddo J. L. Heerspink, Masaomi Nangaku, Yosuke Hirakawa, Yuka Sugawara, Naoki Nakagawa, Yuji Tani, Jun Wada, Hitoshi Sugiyama, Kazuhiko Tsuruya, Toshiaki Nakano, Shoichi Maruyama, Takashi Wada, Kunihiro Yamagata, Ichiei Narita, Kouichi Tamura, Motoko Yanagita, Yoshio Terada, Takashi Shigematsu, Tadashi Sofue, Takafumi Ito, Hirokazu Okada, Naoki Nakashima, Hiromi Kataoka, Kazuhiko Ohe, Mihoko Okada, Seiji Itano, Akira Nishiyama, Eiichiro Kanda, Kohjiro Ueki, Naoki Kashihara

DIABETES CARE 44 ( 11 ) 2542 - 2551 2021年11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：AMER DIABETES ASSOC

OBJECTIVE Randomized controlled trials have shown kidney-protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy, as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitor initiation modify treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients, is unknown. RESEARCH DESIGN AND METHODS Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. RESULTS At baseline, mean age at initiation of the SGLT2 inhibitor (n = 1,033) or other glucose-lowering drug (n = 1,033) was 64.4 years, mean eGFR was 68.1 mL/min per 1.73 m(2), and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs. other drugs 0.75 mL/min/1.73 m(2) per year [0.51 to 1.00]). During a mean follow-up of 24 months, 103 composite kidney outcomes occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26-0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiation of SGLT2 inhibitors (P-heterogeneity >= 0.35). CONCLUSIONS The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.

DOI： 10.2337/dc21-1081

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Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control (vol 12, 727915, 2021) 査読

Dongxiao Zhang, Satoshi Yamaguchi, Xinhao Zhang, Boxuan Yang, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, Takeshi Y. Hiyama, Atsunori Kamiya, Jun Wada

FRONTIERS IN ENDOCRINOLOGY 12 2021年11月

Sodium-Glucose Cotransporter 2 Inhibitors Work as a "Regulator" of Autophagic Activity in Overnutrition Diseases 査読

Kazuhiko Fukushima, Shinji Kitamura, Kenji Tsuji, Jun Wada

FRONTIERS IN PHARMACOLOGY 12 2021年10月

記述言語：英語出版者・発行元：FRONTIERS MEDIA SA

Several large clinical trials have shown renal and cardioprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diabetes patients, and the protective mechanisms need to be elucidated. There have been accumulating studies which report that SGLT2 inhibitors ameliorate autophagy deficiency of multiple organs. In overnutrition diseases, SGLT2 inhibitors affect the autophagy via various signaling pathways, including mammalian target of rapamycin (mTOR), sirtuin 1 (SIRT1), and hypoxia-inducible factor (HIF) pathways. Recently, it turned out that not only stagnation but also overactivation of autophagy causes cellular damages, indicating that therapeutic interventions which simply enhance or stagnate autophagy activity might be a "double-edged sword" in some situations. A small number of studies suggest that SGLT2 inhibitors not only activate but also suppress the autophagy flux depending on the situation, indicating that SGLT2 inhibitors can "regulate" autophagic activity and help achieve the appropriate autophagy flux in each organ. Considering the complicated control and bilateral characteristics of autophagy, the potential of SGLT2 inhibitors as the regulator of autophagic activity would be beneficial in the treatment of autophagy deficiency.

DOI： 10.3389/fphar.2021.761842

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Blood concentrations of tacrolimus upon conversion from rabeprazole to vonoprazan in renal transplant recipients: Correlation with cytochrome P450 gene polymorphisms 査読

Shogo Watari, Motoo Araki, Jun Matsumoto, Kasumi Yoshinaga, Takanori Sekito, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Koichiro Wada, Yasuyuki Kobayashi, Hidemi Takeuchi, Katsuyuki Tanabe, Masashi Kitagawa, Hiroshi Morinaga, Shinji Kitamura, Hitoshi Sugiyama, Noritaka Ariyoshi, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

DRUG METABOLISM AND PHARMACOKINETICS 40 2021年10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 SOC STUDY XENOBIOTICS

We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5*1 and CYP3A5*3 alleles. CYP2C19 geno-types were classified as extensive (*1/*1), intermediate (* 1/*2 and *1/*3) or poor metabolizers (*2/*2, *2/ *3 and *3/*3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5*3/*3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5*1/*1 or CYP3A5*1/*3 groups. Subgroup analyses of CYP3A5*3/*3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5*3/*3 and 2C19*1/*1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus. (C) 2021 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.dmpk.2021.100407

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Feasible kidney donation with living marginal donors, including diabetes mellitus 査読

Kasumi Yoshinaga, Motoo Araki, Koichiro Wada, Takanori Sekito, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Risa Kubota, Shingo Nishimura, Kohei Edamura, Yasuyuki Kobayashi, Katsuyuki Tanabe, Hidemi Takeuchi, Masashi Kitagawa, Shinji Kitamura, Jun Wada, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

IMMUNITY INFLAMMATION AND DISEASE 9 ( 3 ) 1061 - 1068 2021年9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：WILEY

Objectives: To compare the donor outcomes of living donor kidney transplantation between standard donors (SDs) and marginal donors (MDs) including diabetic patients (MD + DM).Methods: MDs were defined according to Japanese guideline criteria: (a) age >70-years, (b) blood pressure <= 130/80 mmHg on hypertension medicine, (c) body mass index >25 to <= 32 kg/m(2), (d) 24-h creatinine clearance >= 70 to <80 ml/min/1.73 m(2), and (e) hemoglobin A1c > 6.2 or <= 6.5 with oral diabetic medicine. Fifty-three of 114 donors were MDs. We compared donor kidney functions until 60 months postoperatively.Results: No kidney function parameters were different between SDs and MDs. When comparing SD and MD + DM, MD + DM had a lower postoperative eGFR (48 vs. 41 (1 (month), p = .02), 49 vs. 40 (12, p < .01), 48 vs. 42 (24, p = .04), 47 vs. 38 (36, p = .01)) and the percentage of residual eGFR (SD vs. MD + DM: 63 vs. 57 (1 (month), p < .01), 63 vs. 57 (2, p < .01), 64 vs. 56 (12, p < .01), 63 vs. 57 (24, p < .01), 63 vs. 52 (36, p = .02)). However, when MD with a single risk factor of DM was compared to SD, the difference disappeared. Nine out of 12 (75%) MD + DM had >= 2 risk factors.Conclusions: Although long-term observation of donor kidney function is necessary, careful MD + DM selection had the potential to expand the donor pool.

DOI： 10.1002/iid3.470

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Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases 査読

Noriko Fujiwara, Mayu Watanabe, Akihiro Katayama, Yohei Noda, Jun Eguchi, Hitomi Kataoka, Shunsuke Kagawa, Jun Wada

CLINICAL CASE REPORTS 9 ( 9 ) 2021年9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：WILEY

Immune checkpoint inhibitor-induced diabetes mellitus is a rare immune-related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes.

DOI： 10.1002/ccr3.4574

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Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2 (vol 11, 5991, 2021) 査読

Tomokazu Nunoue, Satoshi Yamaguchi, Sanae Teshigawara, Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Toshiro Niki, Jun Wada

SCIENTIFIC REPORTS 11 ( 1 ) 2021年9月

Total vascular resistance, augmentation index, and augmentation pressure increase in patients with peripheral artery disease. 査読国際誌

Rika Takemoto, Haruhito A Uchida, Hironobu Toda, Ken Okada, Fumio Otsuka, Hiroshi Ito, Jun Wada

Medicine 100 ( 32 ) e26931 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

ABSTRACT: Peripheral arterial disease (PAD) is one of major vascular diseases which frequently coexists with coronary arterial disease and cerebrovascular disease. The patients with PAD have a poor prognosis when it progresses. A new blood pressure testing device enables to simultaneously measure brachial blood pressure (BP), central BP, and several vascular parameters, with easy and non-invasive, in a short time. Here, we aimed to evaluate these arterial stiffness parameters in patients with PAD.In this study, 243 consecutive patients who were suspected of having PAD and referred to our hospital from September 2016 to June 2019, were registered. Several parameters, such as brachial BP, central BP, aortic pulse wave velocity (aPWV), total vascular resistance (TVR), augmentation index (AI) and augmentation pressure (AP), were determined by Mobil-O-Graph. Ankle-brachial pressure index (ABI) was used to define PAD (ABI ≤ 0.9 as PAD). The relationship between PAD and central BP, aPWV, TVR, AI, or AP were investigated.One hundred sixty-two patients (67%) were categorized as the PAD group and 81 patients (33%) as the non-PAD group. In the PAD group, the systolic brachial BP and central systolic BP were significantly higher than those in the non-PAD group (138 ± 24 mmHg vs 131 ± 19 mmHg, P < .05, 125 ± 22 mmHg vs 119 ± 18 mmHg, P < .05, respectively). TVR, AI, and AP were significantly higher in the PAD group (1785 ± 379 dyn s/cm5 vs 1661 ± 317 dyn s/cm5, P < .05, 26.2 ± 13.0% vs 22.2 ± 13.3%, P < .05, 13.5 ± 9.4 mmHg vs 10.7 ± 7.2 mmHg, P < .05, respectively). No significant differences in diastolic BP, central diastolic BP, and aPWV were found between the groups. Multivariate logistic regression analysis revealed that PAD was significantly associated with TVR, AI, and AP (P < .05, respectively).TVR/AP/AI were significantly higher in the PAD group than in the non-PAD group.

DOI： 10.1097/MD.0000000000026931

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GENOME-WIDE ASSOCIATION STUDY FOR THE ONSET OF CHRONIC KIDNEY DISEASE IN JAPANESE POPULATION 査読

Yuka Sugawara, Yosuke Hirakawa, Hajime Nagasu, Akira Narita, Jun Wada, Takashi Wada, Toshiaki Nakano, Motoko Yanagita, Ichiei Narita, Seizo Koshiba, Gen Tamiya, Masaomi Nangaku, Masayuki Yamamoto, Naoki Kashihara

NEPHROLOGY 26 7 - 8 2021年8月

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