Faculty Profiles - Onishi Yasuhiro

Papers - Onishi Yasuhiro

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Case series showing the safety and changes in lipid profiles of hemodialysis patients with hypertriglyceridemia after pemafibrate administration Reviewed

Rino Okada, Yasuhiro Onishi, Naoya Kobayashi, Hiroyuki Ishihara, Tomohisa Yokoyama, Tomoyo Mifune, Yoshimasa Sakurabu, Ichiro Nojima, Hiroshi Morinaga, Haruhito A. Uchida, Jun Wada

Renal Replacement Therapy 2024.12

A case of renal hypouricemia due to T217M mutation in SLC22A12 incidentally associated with IgA nephropathy. International journal

Yoshimasa Sakurabu, Haruhito A Uchida, Toshihisa Tahara, Tomohiko Asakawa, Haruka Yamasaki, Katsuyoshi Katayama, Shugo Okamoto, Yasuhiro Onishi, Natsumi Matsuoka-Uchiyama, Keiko Tanaka, Hidemi Takeuchi, Kenji Tsuji, Ryoko Umebayashi, Yuki Ohashi, Kimiyoshi Ichida, Jun Wada

Clinical case reports 12 ( 9 ) e9368 2024.9

Language：English Publishing type：Research paper (scientific journal)

A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events.

DOI： 10.1002/ccr3.9368

術前栄養状態と骨格筋評価が腎移植レシピエントの腎予後に与える影響

山野井友昭, 西村慎吾, 関戸崇了, 吉永香澄, 定平卓也, 別宮謙介, 枝村康平, 小林知子, 小林泰之, 大西康博, 竹内英実, 田邊克幸, 森永裕士, 荒木元朗

移植 59 ( 総会臨時 ) 323 - 323 2024.9

Pregnancy and childbirth in Takayasu arteritis in Japan: A nationwide retrospective study.

Takako Miyamae, Manabe Y, Sugihara T, Umezawa N, Yoshifuji H, Tamura N, Abe Y, Furuta S, Nagafuchi H, Ishizaki J, Nakano N, Atsumi T, Karino K, Amano K, Kurasawa T, Ito S, Yoshimi R, Ogawa N, Banno S, Naniwa T, Ito S, Hara A, Hirahara S, Uchida HA, Onishi Y, Murakawa Y, Komagata Y, Nakaoka Y, Harigai M

Modern rheumatology 2024.8

Publishing type：Research paper (scientific journal)

<h4>Objectives</h4>This study aimed to understand the status quo of medical treatments of the primary disease and pregnancy outcomes in patients with Takayasu arteritis (TAK) and children's birth outcomes.<h4>Methods</h4>This study retrospectively enrolled patients with TAK who conceived after the disease onset and were managed at medical facilities participating in the Japan Research Committee of the Ministry of Health, Labor, and Welfare for Intractable Vasculitis.<h4>Results</h4>This study enrolled 51 cases and 68 pregnancies 2019-2021. Of these, 48 cases and 65 pregnancies (95.6%) resulted in delivery and live-born babies. The median age of diagnosis and delivery was 22 and 31, respectively. Preconception therapy included prednisolone (PSL) in 51 (78.5%, median 7.5 mg/day), immunosuppressants in 18 (27.7%), and biologics in 12 (18.5%) pregnancies. Six cases underwent surgical treatment before pregnancy. Medications during pregnancy included PSL in 48 (73.8%, median: 9 mg/day), immunosuppressants in 13 (20.0%), and biologics in 9 (13.8%) pregnancies. Enlargement of an aneurysm was reported in one pregnancy, which might be associated with increased circulating plasma volume. TAK relapsed in 4 (6.2%) and 8 (12.3%) pregnancies during pregnancy and after delivery, respectively. Additionally, 13/62 (20.9%) preterm infants and 17/59 (28.8%) low birth weight infants were observed, and none had serious postnatal abnormalities. Of the 51 confirmed infants, 42 (82.4%) were exclusively breastfed or mixed with formula.<h4>Conclusion</h4>Most pregnancies in TAK were manageable with PSL at ≤10 mg/day. Relapse during pregnancy and postpartum occurred in <20% of pregnancies.

DOI： 10.1093/mr/roae068

岡山市CKDネットワーク(OCKD-NET)2の登録2年後のデータ解析

田中景子, 内田治仁, 大西康博, 岡本修吾, 竹内英実, 辻憲二, 田邊克幸, 森永裕士, 太田康介, 丸山啓輔, 大城義之, 森岡茂, 瀧上慶一, 蒲生直幸, 杉山斉, 和田淳

日本腎臓学会誌 66 ( 4 ) 677 - 677 2024.6

医学生教育における腎生検シミュレーターを用いた腎生検実習の意義

辻憲二, 大西康博, 岡本修吾, 田中景子, 竹内英実, 田邊克幸, 森永裕士, 内田治仁, 和田淳

日本腎臓学会誌 66 ( 4 ) 597 - 597 2024.6

Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3). International journal

Asami Ueno, Yasuhiro Onishi, Koki Mise, Satoshi Yamaguchi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Haruhito A Uchida, Kenichi Shikata, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, Tomokazu Nunoue, Jun Wada

BMJ open diabetes research & care 12 ( 3 ) 2024.5

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. RESEARCH DESIGN AND METHODS: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. RESULTS: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. CONCLUSIONS: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD. TRIAL REGISTRATION NUMBER: UMIN000011525.

DOI： 10.1136/bmjdrc-2024-004237

【肥満と健康障害】肥満関連腎臓病

大西康博, 和田淳

臨床検査 68 ( 5 ) 637 - 643 2024.5

Successful treatment for life threatening recurrent non-traumatic rectus sheath hematoma in a case with microscopic polyangiitis with rapidly progressive glomerulonephritis.

Hiroyuki Nakanoh, Hidemi Takeuchi, Morimoto Shiho, Yuya Terajima, Shugo Okamoto, Yasuhiro Onishi, Keiko Tanaka, Takayuki Katsuyama, Kenji Tsuji, Yoshinori Matsumoto, Katsuyuki Tanabe, Hiroshi Morinaga, Mayu Uka, Koji Tomita, Haruhito A Uchida, Takao Hiraki, Jun Wada

Internal medicine (Tokyo, Japan) 2024.4

Language：English Publishing type：Research paper (scientific journal)

A 68-year-old woman was admitted to our hospital because of a rapid progression of renal dysfunction with positive myeloperoxidase antineutrophil cytoplasmic antibody and was diagnosed with rapidly progressive glomerulonephritis associated with microscopic polyangiitis (MPA). Severe right rectus sheath hematoma (RSH) bleeding from the inferior epigastric artery developed after starting hemodialysis, which required 4 transarterial embolizations due to recurrent bleeding. After additional treatment with methylprednisolone pulse therapy and rituximab, no rebleeding occurred. Although the giant hematoma reached the pelvis, it shrank spontaneously without any intervention. Nontraumatic RSH should therefore be considered when treating patients with multiple risk factors.

DOI： 10.2169/internalmedicine.3239-23

Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes

Kano, Y., Yamaguchi, S., Mise, K., Kawakita, C., Onishi, Y., Kurooka, N., Sugawara, R., Albuayjan, H.H.H., Nakatsuka, A., Eguchi, J., Wada, J.

Kidney360 5 ( 2 ) 2024.2

当院における生体腎移植ドナーの術後フォローアップ状況

山野井友昭, 西村慎吾, 関戸崇了, 吉永香澄, 丸山雄樹, 定平卓也, 別宮謙介, 枝村康平, 小林知子, 小林泰之, 大西康博, 竹内英実, 田邊克幸, 森永裕士, 荒木元朗

日本臨床腎移植学会プログラム・抄録集 57回 208 - 208 2024.2

当院における先行的生体腎移植の検討

吉永香澄, 関戸崇了, 丸山雄樹, 山野井友昭, 西村慎吾, 富永悠介, 定平卓也, 片山聡, 岩田健宏, 大西康博, 竹内英実, 田邊克幸, 森永裕士, 和田淳, 枝村康平, 小林知子, 小林泰之, 荒木元朗

日本臨床腎移植学会プログラム・抄録集 57回 210 - 210 2024.2

Kidney Veno-Muscular Characteristics and Kidney Disease Progression: A Native Kidney-Biopsy Study. International journal

Kenji Tsuji, Hiroyuki Nakanoh, Kensaku Takahashi, Takafumi Morita, Yizhen Sang, Kazuhiko Fukushima, Natsumi Matsuoka-Uchiyama, Yasuhiro Onishi, Haruhito A Uchida, Shinji Kitamura, Jun Wada

Kidney medicine 5 ( 12 ) 100733 - 100733 2023.12

Language：English Publishing type：Research paper (scientific journal)

RATIONALE & OBJECTIVE: Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants are poorly understood. In the present study, we investigated kidney prognostic values of VMC variants. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled. PREDICTORS: VMC variants; inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score. OUTCOMES: A decline in estimated glomerular filtration rate (eGFR) ≥40% from the baseline or commencement of kidney replacement therapy. ANALYTICAL APPROACH: Cox proportional hazards model. RESULTS: Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory-VMC, and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed 2 VMC variants. Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both inflammatory-VMC and hyper-VMC. A Cox proportional hazards analysis revealed that inflammatory-VMC (but not hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR, and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio, 1.97; 95% confidence interval, 1.00-3.91). LIMITATIONS: Single-center study and small sample size. CONCLUSIONS: Assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy. PLAIN-LANGUAGE SUMMARY: Assessment of kidney biopsies provides crucial information for diagnosis, disease activity, and prognostic value. Kidney-biopsy specimens occasionally contain veno-muscular complex (VMC), which consists of muscle tissues around the kidney venous system. Currently, the role of VMC in kidney health and diseases and the clinical significance of VMC variants are poorly understood. In the present study, we have shown that an infiltration of ≥80 inflammatory cells/mm2-VMC area (inflammatory-VMC) is independently associated with kidney disease progression after adjustments for known risk factors of progression. Therefore, assessment of inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.

DOI： 10.1016/j.xkme.2023.100733

検尿異常の精査中に発見したIgA腎症に腎性低尿酸血症が合併した1例

櫻武敬真, 内田治仁, 田原稔久, 山崎遥香, 大西康博, 田中景子, 竹内英実, 辻憲二, 梅林亮子, 和田淳

日本腎臓学会誌 65 ( 6-W ) 810 - 810 2023.9

当院における腎移植後悪性腫瘍の検討

山野井友昭, 西村慎吾, 関戸崇了, 吉永香澄, 丸山雄樹, 定平卓也, 枝村康平, 小林知子, 小林泰之, 大西康博, 竹内英実, 田邊克幸, 森永裕士, 和田淳, 荒木元朗

移植 58 ( 総会臨時 ) 262 - 262 2023.9

免疫学的ハイリスク腎移植における低用量リツキシマブを用いた脱感作療法とサイトメガロウイルス感染症 5年間の追跡調査

吉永香澄, 関戸崇了, 丸山雄樹, 山野井友昭, 西村慎吾, 大西康博, 竹内英実, 田邊克幸, 森永裕士, 枝村康平, 小林知子, 小林泰之, 和田淳, 荒木元朗

移植 58 ( 総会臨時 ) 307 - 307 2023.9

【腎臓疾患のメカニズム解明に向けた糖鎖生物学的アプローチ】糖尿病性腎臓病における糖鎖異常とその病態的意義

大西康博, 和田淳

腎臓内科 18 ( 1 ) 24 - 31 2023.7

【糖尿病性腎臓病・腎硬化症の病態と診療】糖尿病性腎臓病・腎硬化症のバイオマーカー

大西康博, 和田淳

月刊糖尿病 15 ( 4 ) 56 - 62 2023.6

岡山市CKDネットワーク(OCKD-NET)におけるCKD病診連携12年後の追跡調査

大西康博, 内田治仁, 田中景子, 岡本修吾, 竹内英実, 辻憲二, 田邊克幸, 森永裕士, 喜多村真治, 前島洋平, 太田康介, 丸山啓輔, 大城義之, 森岡茂, 瀧上慶一, 蒲生直幸, 杉山斉, 和田淳

日本腎臓学会誌 65 ( 3 ) 240 - 240 2023.5

岡山市CKDネットワーク(OCKD-NET)2の登録時データ解析 OCKD-NET1との比較

田中景子, 内田治仁, 大西康博, 岡本修吾, 竹内英実, 辻憲二, 田邊克幸, 森永裕士, 太田康介, 丸山啓輔, 大城義之, 森岡茂, 瀧上慶一, 蒲生直幸, 杉山斉, 和田淳

日本腎臓学会誌 65 ( 3 ) 268 - 268 2023.5

医学生に対する腎セミナー開催についての検討

辻憲二, 岡本修吾, 大西康博, 田中景子, 竹内英実, 田邊克幸, 森永裕士, 内田治仁, 喜多村真治, 和田淳

日本腎臓学会誌 65 ( 3 ) 326 - 326 2023.5

岡山市CKDネットワーク(OCKD-NET)におけるCKD病診連携12年後の追跡調査

大西康博, 内田治仁, 田中景子, 岡本修吾, 竹内英実, 辻憲二, 田邊克幸, 森永裕士, 喜多村真治, 前島洋平, 太田康介, 丸山啓輔, 大城義之, 森岡茂, 瀧上慶一, 蒲生直幸, 杉山斉, 和田淳

日本腎臓学会誌 65 ( 3 ) 240 - 240 2023.5

医学生に対する腎セミナー開催についての検討

辻憲二, 岡本修吾, 大西康博, 田中景子, 竹内英実, 田邊克幸, 森永裕士, 内田治仁, 喜多村真治, 和田淳

日本腎臓学会誌 65 ( 3 ) 326 - 326 2023.5

The Effect of Medical Cooperation in the CKD Patients: 10-Year Multicenter Cohort Study. International journal

Yasuhiro Onishi, Haruhito A Uchida, Yohei Maeshima, Yuka Okuyama, Nozomu Otaka, Haruyo Ujike, Keiko Tanaka, Hidemi Takeuchi, Kenji Tsuji, Masashi Kitagawa, Katsuyuki Tanabe, Hiroshi Morinaga, Masaru Kinomura, Shinji Kitamura, Hitoshi Sugiyama, Kosuke Ota, Keisuke Maruyama, Makoto Hiramatsu, Yoshiyuki Oshiro, Shigeru Morioka, Keiichi Takiue, Kazuyoshi Omori, Masaki Fukushima, Naoyuki Gamou, Hiroshi Hirata, Ryosuke Sato, Hirofumi Makino, Jun Wada

Journal of personalized medicine 13 ( 4 ) 2023.3

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: While chronic kidney disease (CKD) is one of the most important contributors to mortality from non-communicable diseases, the number of nephrologists is limited worldwide. Medical cooperation is a system of cooperation between primary care physicians and nephrological institutions, consisting of nephrologists and multidisciplinary care teams. Although it has been reported that multidisciplinary care teams contribute to the prevention of worsening renal functions and cardiovascular events, there are few studies on the effect of a medical cooperation system. METHODS: We aimed to evaluate the effect of medical cooperation on all-cause mortality and renal prognosis in patients with CKD. One hundred and sixty-eight patients who visited the one hundred and sixty-three clinics and seven general hospitals of Okayama city were recruited between December 2009 and September 2016, and one hundred twenty-three patients were classified into a medical cooperation group. The outcome was defined as the incidence of all-cause mortality, or renal composite outcome (end-stage renal disease or 50% eGFR decline). We evaluated the effects on renal composite outcome and pre-ESRD mortality while incorporating the competing risk for the alternate outcome into a Fine-Gray subdistribution hazard model. RESULTS: The medical cooperation group had more patients with glomerulonephritis (35.0% vs. 2.2%) and less nephrosclerosis (35.0% vs. 64.5%) than the primary care group. Throughout the follow-up period of 5.59 ± 2.78 years, 23 participants (13.7%) died, 41 participants (24.4%) reached 50% decline in eGFR, and 37 participants (22.0%) developed end-stage renal disease (ESRD). All-cause mortality was significantly reduced by medical cooperation (sHR 0.297, 95% CI 0.105-0.835, p = 0.021). However, there was a significant association between medical cooperation and CKD progression (sHR 3.069, 95% CI 1.225-7.687, p = 0.017). CONCLUSION: We evaluated mortality and ESRD using a CKD cohort with a long-term observation period and concluded that medical cooperation might be expected to influence the quality of medical care in the patients with CKD.

DOI： 10.3390/jpm13040582

Serum sCD40L and IL-31 in Association with Early Phase of IgA Nephropathy. International journal

Keiko Tanaka, Hitoshi Sugiyama, Hiroshi Morinaga, Masashi Kitagawa, Yuzuki Kano, Yasuhiro Onishi, Koki Mise, Katsuyuki Tanabe, Haruhito A Uchida, Jun Wada

Journal of clinical medicine 12 ( 5 ) 2023.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: IgA nephropathy (IgAN) is a major cause of chronic glomerulonephritis worldwide. T cell dysregulation has been reported to contribute to the pathogenesis of IgAN. Methods We measured a broad range of Th1, Th2 and Th17 cytokines in the serum of IgAN patients. We searched for significant cytokines, which were associated with clinical parameters and histological scores in IgAN patients. RESULTS: Among 15 cytokines, the levels of soluble CD40L (sCD40L) and IL-31 were higher in IgAN patients and were significantly associated with a higher estimated glomerular filtration rate (eGFR), a lower urinary protein to creatinine ratio (UPCR), and milder tubulointerstitial lesions (i.e., the early phase of IgAN). Multivariate analysis revealed that serum sCD40L was an independent determinant of a lower UPCR after adjustment for age, eGFR, and mean blood pressure (MBP). CD40, a receptor of sCD40L, has been reported to be upregulated on mesangial cells in IgAN. The sCD40L/CD40 interaction may directly induce inflammation in mesangial areas and may therefore be involved in the development of IgAN. CONCLUSIONS: The present study demonstrated the significance of serum sCD40L and IL-31 in the early phase of IgAN. Serum sCD40L may be a marker of the beginning of inflammation in IgAN.

DOI： 10.3390/jcm12052023

【腸腎連関に関する最近の話題】糖鎖生物学からみた腸腎連関

大西康博, 和田淳

日本腎臓学会誌 65 ( 2 ) 67 - 73 2023.3

【糖尿病性腎臓病治療の現状と展望-透析導入患者減少のために-】DKDの診断と新規バイオマーカーの開発

和田淳, 三瀬広記, 今村麻理子, 大西康博

Progress in Medicine 43 ( 2 ) 101 - 104 2023.2

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. International journal

Hidemi Takeuchi, Haruhito A Uchida, Katsuyoshi Katayama, Natsumi Matsuoka-Uchiyama, Shugo Okamoto, Yasuhiro Onishi, Yuka Okuyama, Ryoko Umebayashi, Kodai Miyaji, Akiko Kai, Izumi Matsumoto, Keiko Taniguchi, Fukiko Yamashita, Tsutomu Emi, Hitoshi Sugiyama, Jun Wada

Medicina (Kaunas, Lithuania) 58 ( 11 ) 2022.10

Language：English Publishing type：Research paper (scientific journal)

Background and Objectives: Mimasaka city is a relatively small city with a population of 28,381, and an aging rate (≥65 years old) of 38.9%, where only one nephrology clinic is available. Since 2013, the city has conducted its own unique lifestyle intervention for the participants of the National Health Insurance specific medical health checkup, aiming to prevent the progression of chronic kidney disease (CKD) severity. Materials and Methods: The persons in National Health Insurance specific medical health checkup (40-74 years old) conducted in Mimasaka city in 2013, with eGFR less than 50 mL/min/1.73 m² or 50-90 mL/min/1.73 m² with urine dipstick protein 1+ or more, were registered for the CKD follow-up project, as high-risk subjects for advanced renal dysfunction. Municipal workers directly visited the subjects' homes to provide individual health guidance and encourage medical consultation. We aimed to examine the effect of home-visit intervention on the changes of renal function and related factors until 2017. Results: The number of the high-risk subjects who continuously received the health checkup until 2017 was 63, and only 23 (36.5%) visited a medical institution in the first year. The eGFR decreased by only 0.4 mL/min/1.73 m²/year, and the subjects with urinary protein 1+ or higher decreased significantly from 20 (31.7%) to 9 (14.3%) (p = 0.034) in the high-risk subjects. The changes in eGFR and urinary protein was almost in the same fashion regardless of their medical institution visits. Next, we examined the effects of various factors on ΔeGFR, the changes of eGFR from 2013 to 2017, by multivariate linear regression analysis. The effects of medical institution visit were not significant, and the degree of urinary protein (coefficient B: 4.503, β: 0.705, p < 0.001), age (coefficient B: 4.753, β: 0.341, p = 0.004), and smoking (coefficient B: 5.878, β: 0.295, p = 0.031) had independent significant effects, indicating that they were the factors exacerbating the decrease in eGFR from the baseline. Conclusions: The personalized lifestyle intervention by home-visit in CKD follow-up project showed the possibility of beneficial effects on the deterioration of renal function. This may be an efficient method to change behavior in a small community with limited medical resources.

DOI： 10.3390/medicina58111529

Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study. International journal

Yuka Sugawara, Yosuke Hirakawa, Koki Mise, Kosuke Kashiwabara, Ko Hanai, Satoshi Yamaguchi, Akihiro Katayama, Yasuhiro Onishi, Yui Yoshida, Naoki Kashihara, Yutaka Matsuyama, Tetsuya Babazono, Masaomi Nangaku, Jun Wada

Biomarkers in medicine 16 ( 10 ) 759 - 770 2022.5

Language：English Publishing type：Research paper (scientific journal)

Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of ten cytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rβ, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n = 777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n = 69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5 ml/min/1.73 m2/year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.

DOI： 10.2217/bmm-2021-1104

【腎臓病の病態解明とバイオマーカー研究】慢性腎臓病における糖鎖生物学とバイオマーカーへの応用

大西康博, 和田淳

臨床化学 51 ( 2 ) 67 - 74 2022.4

糖尿病性腎臓病患者における糖鎖バイオロジー

大西康博, 和田淳

腎臓内科 15 ( 1 ) 117 - 123 2022.1

Development of Urinary Diagnostic Biomarker for IgA Nephropathy by Lectin Microarray. International journal

Yasuhiro Onishi, Koki Mise, Chieko Kawakita, Haruhito A Uchida, Hitoshi Sugiyama, Ryosuke Sugawara, Satoshi Yamaguchi, Michihiro Yoshida, Toshiharu Mitsuhashi, Masao Yamada, Jun Hirabayashi, Jun Wada

American journal of nephrology 53 ( 1 ) 10 - 20 2022

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: The pathogenic roles of aberrantly glycosylated IgA1 have been reported. However, it is unexplored whether the profiling of urinary glycans contributes to the diagnosis of IgAN. METHODS: We conducted a retrospective study enrolling 493 patients who underwent renal biopsy at Okayama University Hospital between December 2010 and September 2017. We performed lectin microarray in urine samples and investigated whether c-statistics of the reference standard diagnosis model employing hematuria, proteinuria, and serum IgA were improved by adding the urinary glycan intensity. RESULTS: Among 45 lectins, 3 lectins showed a significant improvement of the models: Amaranthus caudatus lectin (ACA) with the difference of c-statistics 0.038 (95% CI: 0.019-0.058, p < 0.001), Agaricus bisporus lectin (ABA) 0.035 (95% CI: 0.015-0.055, p < 0.001), and Maackia amurensis lectin (MAH) 0.035 (95% CI: 0.015-0.054, p < 0.001). In 3 lectins, each signal plus reference standard showed good reclassification (category-free NRI and relative IDI) and good model fitting associated with the improvement of AIC and BIC. Stratified by eGFR, the discriminatory ability of ACA plus reference standard was maintained, suggesting the robust renal function-independent diagnostic performance of ACA. By decision curve analysis, there was a 3.45% net benefit by adding urinary glycan intensity of ACA to the reference standard at the predefined threshold probability of 40%. CONCLUSIONS: The reduction of Gal(β1-3)GalNAc (T-antigen), Sia(α2-3)Gal(β1-3)GalNAc (Sialyl T), and Sia(α2-3)Gal(β1-3)Sia(α2-6)GalNAc (disialyl-T) was suggested by binding specificities of 3 lectins. C1GALT1 and COSMC were responsible for the biosynthesis of these glycans, and they were known to be downregulated in IgAN. The urinary glycan analysis by ACA is a useful and robust noninvasive strategy for the diagnosis of IgAN.

DOI： 10.1159/000520998

The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study. International journal

Natsumi Matsuoka-Uchiyama, Haruhito A Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenichi Shikata, Jun Wada

Journal of diabetes research 2022 3157841 - 3157841 2022

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. METHODS: We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a ≥40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. RESULTS: Among the 527 participants, 110 reached a ≥40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0073, 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p = 0.0241, 0.0352, and 0.0474, respectively). CONCLUSIONS: Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM.

DOI： 10.1155/2022/3157841

Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy. International journal

Chieko Kawakita, Koki Mise, Yasuhiro Onishi, Hitoshi Sugiyama, Michihiro Yoshida, Masao Yamada, Jun Wada

Scientific reports 11 ( 1 ) 3394 - 3394 2021.2

Language：English Publishing type：Research paper (scientific journal)

In IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11-7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11-4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(β1-4)GlcNAc and high-mannose including Man(α1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike's information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.

DOI： 10.1038/s41598-020-77736-1

The disease subsets in giant cell arteritis: data from an international observational cohort (Diagnostic and Classification Criteria in Vasculitis Study-DCVAS).

大西康博, 内田治仁

月刊リウマチ科 65 ( 1 ) 2021

Vasohibin-2 Aggravates Development of Ascending Aortic Aneurysms But Not Abdominal Aortic Aneurysms Nor Atherosclerosis in ApoE Deficient Mice. International journal

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

American journal of hypertension 34 ( 5 ) 467 - 475 2020.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Vasohibin-2 (VASH2) has been isolated as a homologue of vasohibin-1 (VASH1) that promote angiogenesis counteracting with VASH1. Chronic angiotensin II (AngII) infusion promotes both ascending and abdominal aortic aneurysms (AAs) in mice. The present study aimed to investigate whether exogenous VASH2 influenced AngII-induced vascular pathology in apolipoprotein E deficient (ApoE -/-) mice. METHODS: Male, ApoE -/- mice (9 to 14 weeks old) were injected with Ad LacZ or Ad VASH2. After a week, saline or AngII (1,000 ng/kg/min) was infused into the mice subcutaneously via mini-osmotic pumps for 3 weeks. Consequently, all these mice were divided into 4 groups: saline + LacZ (n=5), saline + VASH2 (n=5), AngII + LacZ (n=18), and AngII + VASH2 (n=17). RESULTS: Exogenous VASH2 had no significant effect on ex vivo maximal diameters of abdominal aortas (AngII + LacZ; 1.67±0.17 mm, AngII + VASH2; 1.52±0.16 mm, n.s.) or elastin fragmentation and accumulation of inflammatory cells. Conversely, exogenous VASH2 significantly increased intima areas of aortic arches (AngII + LacZ; 16.6±0.27 mm 2, AngII + VASH2; 18.6±0.64 mm 2, p=0.006). VASH2 effect of AngII-induced ascending AAs was associated with increased cleaved caspase-3 abundance. AngII-induced atherosclerosis was not altered by VASH2. CONCLUSION: The present study demonstrated that augmented VASH2 expression had no effect of AngII-induced abdominal AAs or atherosclerosis, while increasing dilation in the ascending aorta.

DOI： 10.1093/ajh/hpaa181

The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2/HO-1 Pathway. Reviewed International journal

Yoshiko Hada, Haruhito A Uchida, Nozomu Otaka, Yasuhiro Onishi, Shugo Okamoto, Mariko Nishiwaki, Rika Takemoto, Hidemi Takeuchi, Jun Wada

International journal of molecular sciences 21 ( 12 ) 2020.6

Language：English Publishing type：Research paper (scientific journal)

The world faces the serious problem of aging. In this study, we aimed to investigate the effect of chlorogenic acid (CGA) on vascular senescence. C57/BL6 female mice that were 14 ± 3 months old were infused with either Angiotensin II (AngII) or saline subcutaneously for two weeks. These mice were administered CGA of 20 or 40 mg/kg/day, or saline via oral gavage. AngII infusion developed vascular senescence, which was confirmed by senescence associated-β-galactosidase (SA-β-gal) staining. CGA administration attenuated vascular senescence in a dose-dependent manner, in association with the increase of Sirtuin 1 (Sirt1) and endothelial nitric oxide synthase (eNOS), and with the decrease of p-Akt, PAI-1, p53, and p21. In an in vitro study, with or without pre-treatment of CGA, Human Umbilical Vein Endothelial Cells (HUVECs) were stimulated with H2O2 for an hour, then cultured in the absence or presence of 0.5-5.0 μM CGA for the indicated time. Endothelial cell senescence was induced by H2O2, which was attenuated by CGA treatment. Pre-treatment of CGA increased Nrf2 in HUVECs. After H2O2 treatment, translocation of Nrf2 into the nucleus and the subsequent increase of Heme Oxygenase-1 (HO-1) were observed earlier in CGA-treated cells. Furthermore, the HO-1 inhibitor canceled the beneficial effect of CGA on vascular senescence in mice. In conclusion, CGA exerts a beneficial effect on vascular senescence, which is at least partly dependent on the Nuclear factor erythroid 2-factor 2 (Nrf2)/HO-1 pathway.

DOI： 10.3390/ijms21124527

Impaired mental health status in patients with chronic kidney disease is associated with estimated glomerular filtration rate decline. Reviewed International journal

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 2019.9

Language：English Publishing type：Research paper (scientific journal)

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

Olmesartan ameliorates hepatic insufficiency and serum TGF-β1 level in hypertensive patients with non-alcoholic fatty liver disease

Nozomu Otaka, Haruhito A. Uchida, Ryoko Umebayashi, Yasuhiro Onishi, Yuka Okuyama, Hidemi Takeuchi, Yuki Kakio, Hitoshi Sugiyama, Fumio Kondo, Kazushi Harada, Hisanao Norii, Yuko Okazaki, Taro Sugimoto, Hiroo Hashimoto, Jun Wada

Therapeutic Research 39 ( 2 ) 159 - 166 2018

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