Faculty Profiles - FURUHASHI Kazuhiro

Protocol for a Phase 1, Open-Label, Multiple-Center, Dose-Escalation Study to Evaluate the Safety and Tolerability of ADR-001 in the Treatment of Immunoglobulin A Nephropathy. Reviewed International journal

Akihito Tanaka, Kazuhiro Furuhashi, Kumiko Fujieda, Kayaho Maeda, Shoji Saito, Tetsushi Mimura, Yosuke Saka, Tomohiko Naruse, Takuji Ishimoto, Tomoki Kosugi, Fumie Kinoshita, Yachiyo Kuwatsuka, Shinobu Shimizu, Yasuhiro Nakai, Shoichi Maruyama

Frontiers in medicine Vol. 9 page： 883168 - 883168 2022.5

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

Introduction: Immunoglobulin A (IgA) nephropathy is a disease that presents with urinary symptoms such as glomerular hematuria and urinary protein positivity, with predominant deposition of IgA in the mesangial region of the glomerulus. Corticosteroids are mainly used for treatment; however, infection is a serious adverse event, and evidence regarding therapeutic efficacy is insufficient, thus new treatments are strongly desired. Mesenchymal stem cells (MSCs) contribute to the amelioration of inflammation and recovery of organ function in inflammatory environments by converting the character of leukocytes from inflammatory to anti-inflammatory and inducing the proliferation and differentiation of organ component cells, respectively. These properties of MSCs have led to their clinical application in various inflammatory diseases, but this study is the first clinical trial of MSCs for refractory glomerulonephritis in the world. This study is registered and assigned the number, jRCT2043200002 and NCT04342325. Methods: This will be a phase 1, open-label, multiple-center, dose-escalation study of adult patients with refractory IgA nephropathy resistant to or difficult to treat with existing therapies. ADR-001 will be administered intravenously to from three to six patients at a dose of 1 × 108 cells once in the first cohort and to six patients twice at 2-week intervals in the second cohort, and observation will continue until 52 weeks. The primary endpoint will be the evaluation of adverse events up to 6 weeks after the start of ADR-001 administration. Secondary endpoints will be the respective percentages of patients with adverse events, clinical remission, partial remission, remission of urine protein, remission of hematuria, time to remission, changes in urine protein, hematuria, and estimated glomerular filtration rate. Results: Following the administration of ADR-001 to patients with IgA nephropathy, the respective percentages of patients with adverse events, asymptomatic pulmonary emboli, clinical remission, partial remission, urine protein remission, hematuria remission, their time to remission, changes in urine protein, hematuria, and glomerular filtration rate will be determined. Conclusion: This study will evaluate the safety and tolerability of ADR-001 and confirm its therapeutic efficacy in adult patients with refractory IgA nephropathy.

DOI： 10.3389/fmed.2022.883168

Monocytes transition to monocyte‐macrophages within the inflamed vasculature via CCR2 on monocytes and endothelial TNFR2 Reviewed

Vijayashree Sathyanarayana Mysore, Suhail Tahir, Kazuhiro Furuhashi, Jatin Arora, Florencia Rosetti, Xavier Cullere, Pascal Yazbeck, Miroslav Sekulic, Madeleine E Lemieux, Soumya Raychaudhuri, Bruce Horwitz, Tanya Mayadas

Vol. 36 2022.5

血液透析歴30年を超えてから、夫婦間血液型不適合生体腎移植を施行した1例

田中章仁, 齋藤尚二, 古橋和拡, 安田宜成, 藤田高史, 加藤真史, 丸山彰一

日本透析医学会雑誌 Vol. 55 ( Suppl.1 ) page： 469 - 469 2022.5

腎移植後の患者におけるSARS-CoV-2 mRNAワクチン接種後の抗体獲得率

藤枝久美子, 田中章仁, 菊地良介, 高井奈美, 齋藤尚二, 安田宜成, 藤田高史, 加藤真史, 古橋和拡, 丸山彰一

日本透析医学会雑誌 Vol. 55 ( Suppl.1 ) page： 531 - 531 2022.5

当院通院中の腎移植後の患者におけるSARS-CoV-2 mRNAワクチン接種後の抗体獲得率

藤枝久美子, 田中章仁, 菊地良介, 高井奈美, 齋藤尚二, 安田宜成, 藤田高史, 加藤真史, 古橋和拡, 丸山彰一

日本腎臓学会誌 Vol. 64 ( 3 ) page： 235 - 235 2022.5

当院通院中の腎移植後の患者におけるSARS-CoV-2 mRNAワクチン接種後の抗体獲得率

藤枝久美子, 田中章仁, 菊地良介, 高井奈美, 齋藤尚二, 安田宜成, 藤田高史, 加藤真史, 古橋和拡, 丸山彰一

日本腎臓学会誌 Vol. 64 ( 3 ) page： 235 - 235 2022.5

当院通院中の腎移植レシピエントにおけるSARS-CoV-2 mRNAワクチン接種後の抗体価の推移についての検討

田中章仁, 藤枝久美子, 菊地良介, 高井奈美, 齋藤尚二, 安田宜成, 藤田高史, 加藤真史, 古橋和拡, 丸山彰一

日本腎臓学会誌 Vol. 64 ( 3 ) page： 235 - 235 2022.5

当院通院中の腎移植レシピエントにおけるSARS-CoV-2 mRNAワクチン接種後の抗体価の推移についての検討

田中章仁, 藤枝久美子, 菊地良介, 高井奈美, 齋藤尚二, 安田宜成, 藤田高史, 加藤真史, 古橋和拡, 丸山彰一

日本腎臓学会誌 Vol. 64 ( 3 ) page： 235 - 235 2022.5

Antibody response to double SARS-CoV-2 mRNA vaccination in Japanese kidney transplant recipients Reviewed

Fujieda, K; Tanaka, A; Kikuchi, R; Takai, N; Saito, S; Yasuda, Y; Fujita, T; Kato, M; Furuhashi, K; Maruyama, S

SCIENTIFIC REPORTS Vol. 12 ( 1 ) page： 6850 2022.4

Language：English Publisher：Scientific Reports

Immunocompromised patients, especially those who undergo kidney transplantation, have lower antibody levels following SARS-CoV-2 mRNA vaccination. The situation of transplant treatment, such as transplant source and immunosuppressive drugs, is different in Japan than that in other countries. Therefore, it is necessary to clarify whether antibody acquisition rates differ between Japan and other countries. This retrospective study included patients with post-kidney transplant who were attending at the Nagoya University Hospital. The anti-SARS-CoV-2 IgG antibody titers were measured between 3 weeks and 3 months after vaccination. Seventy-three patients (45 men and 28 women) were included. Of these, 23 (31.5%) showed antibody presence, and the rates of antibody acquisition were very low than those in the control group (100.0% vs. 31.5%, P < 0.05). Antibody acquisition rates were associated with body mass index (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.04–1.39, P < 0.05) and the duration between transplantation and vaccination (OR: 1.01, 95% CI: 1.00–1.02, P < 0.05). The immunosuppressive drugs used were: prednisolone in all cases, tacrolimus in 89.0%, cyclosporine in 9.6%, and mofetil mycophenolate in 97.3%. None of the patients were excluded from receiving two doses of the vaccine due to adverse effects. The study indicated that vaccination-induced antibody acquisition rates against SARS-CoV-2 were extremely low in Japanese patients who underwent post-kidney transplantation. Thus, despite two doses of vaccination, it is necessary to closely monitor infection control in such patients.

DOI： 10.1038/s41598-022-10510-7

A novel renal perivascular mesenchymal cell subset gives rise to fibroblasts distinct from classic myofibroblasts Reviewed

Shun Minatoguchi, Shoji Saito, Kazuhiro Furuhashi, Yuriko Sawa, Masaki Okazaki, Yuko Shimamura, Ahmad Baseer Kaihan, Yusaku Hashimoto, Yoshinari Yasuda, Akitoshi Hara, Yasuyuki Mizutani, Ryota Ando, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Nobutoshi Esaki, Makoto Matsuyama, Yukihiro Shiraki, Hiroki Kobayashi, Naoya Asai, Atsushi Enomoto, Shoichi Maruyama

Scientific Reports Vol. 12 ( 1 ) page： 5389 2022.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Perivascular mesenchymal cells (PMCs), which include pericytes, give rise to myofibroblasts that contribute to chronic kidney disease progression. Several PMC markers have been identified; however, PMC heterogeneity and functions are not fully understood. Here, we describe a novel subset of renal PMCs that express Meflin, a glycosylphosphatidylinositol-anchored protein that was recently identified as a marker of fibroblasts essential for cardiac tissue repair. Tracing the lineage of Meflin+ PMCs, which are found in perivascular and periglomerular areas and exhibit renin-producing potential, showed that they detach from the vasculature and proliferate under disease conditions. Although the contribution of Meflin+ PMCs to conventional α-SMA+ myofibroblasts is low, they give rise to fibroblasts with heterogeneous α-SMA expression patterns. Genetic ablation of Meflin+ PMCs in a renal fibrosis mouse model revealed their essential role in collagen production. Consistent with this, human biopsy samples showed that progressive renal diseases exhibit high Meflin expression. Furthermore, Meflin overexpression in kidney fibroblasts promoted bone morphogenetic protein 7 signals and suppressed myofibroblastic differentiation, implicating the roles of Meflin in suppressing tissue fibrosis. These findings demonstrate that Meflin marks a PMC subset that is functionally distinct from classic pericytes and myofibroblasts, highlighting the importance of elucidating PMC heterogeneity.

DOI： 10.1038/s41598-022-09331-5

腎移植レシピエントにおけるSARS-CoV-2 mRNAワクチン接種後の抗体獲得率

安田宜成, 田中章仁, 菊地良介, 高井奈美, 齋藤尚二, 藤田高史, 加藤真史, 古橋和拡, 丸山彰一

移植 Vol. 57 ( Supplement ) page： s270_3 - s270_3 2022

Language：Japanese Publisher：一般社団法人日本移植学会

【背景】腎移植レシピエントでは免疫抑制療法のためSARS-CoV-2 mRNA vaccinationによる抗体獲得率が低いと報告されている。本邦では諸外国と比較し、生体腎移植が多く、免疫抑制薬の治療レジメなどが異なる。日本人腎移植レシピエントのワクチン接種後の交代獲得率を調査した。【方法】対象は名古屋大学医学部付属病院へ通院中の日本人腎移植レシピエントのうち、SARS-CoV-2 mRNAワクチンを受けて、抗体価を測定した106名。抗体価は2回のワクチン接種後3週間から3か月の間にSARS-CoV-2 IgG II Quant Reagent Kit(R)により測定し、50 AU/mL以上を陽性とした。【結果】対象者106名中で陽性は41名（38.6%）であった。抗体獲得率に関連する因子として、BMI（OR 1.24, 95% CI 1.08-1.41, P＜0.05）、移植からの期間（OR 1.01, 95% CI 1.00-1.02, P＜0.05）、eGFR（OR 1.07, 95% CI 1.02-1.11, P＜0.05）が関連した。【結論】腎移植レシピエントはSARS-CoV-2 mRNAワクチン接種後の抗体獲得率が低く、ワクチン接種後も厳重な感染対策を継続しなければならない。加えて免疫抑制治療中の患者において抗体獲得率を高めるSARS-CoV-2 mRNAワクチン接種方法の検討が必要である。

DOI： 10.11386/jst.57.supplement_s270_3

CiNii Research

A Case of TAFRO Syndrome with Two Consecutive Renal Biopsies Following the Pathological Course of the Kidney Reviewed

Kato, N; Hasegawa, T; Muto, R; Tanaka, A; Sato, Y; Maeda, K; Furuhashi, K; Saito, S; Kosugi, T; Maruyama, S

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Vol. 32 ( 10 ) page： 823 - 824 2021.10

ABO不適合生体腎移植後にisolated v lesionを認め、1年後にTCMRと診断された1例

田中章仁, 前田佳哉輔, 齋藤尚二, 古橋和拡, 加藤規利, 安田宜成, 加藤真史, 藤田高史, 丸山彰一

日本腎臓学会誌 Vol. 63 ( 6-W ) page： 835 - 835 2021.9

当院の生体腎移植術前検査における、麻疹、風疹、ムンプス、水痘帯状疱疹ウィルス抗体価の検討

田中章仁, 藤島由貴, 古橋和拡, 齋藤尚二, 安田宜成, 石田昇平, 藤田高史, 加藤真史, 丸山彰一

日本腎臓学会誌 Vol. 63 ( 4 ) page： 483 - 483 2021.6

手術前に低ナトリウム血症を補正して生体腎移植に臨んだ1例

田中章仁, 龍華章裕, 古橋和拡, 齋藤尚二, 鈴木康弘, 安田宜成, 藤田高史, 加藤真史, 丸山彰一

日本透析医学会雑誌 Vol. 54 ( Suppl.1 ) page： 325 - 325 2021.5

当院へ生体腎移植目的で紹介された症例の手術中止、延期に関連する因子の検討

田中章仁, 齋藤尚二, 古橋和拡, 安田宜成, 藤田高史, 加藤真史, 丸山彰一

日本透析医学会雑誌 Vol. 53 ( Suppl.1 ) page： 562 - 562 2020.10

Acute kidney injury and cytokines

Furuhashi K

Acute Kidney Injury and Regenerative Medicine page： 333 - 351 2020.1

Language：Japanese Publisher：Acute Kidney Injury and Regenerative Medicine

Cytokines and chemokines are potential signaling molecules that maintain homeostasis by activating intracellular communication. Cytokines orchestrate various processes, ranging from cellular survival, proliferation, and chemotaxis for tissue repair to regulation of inflammation. Extracellular vesicles (EVs), which are cell-derived membrane particles such as exosomes and microvesicles, may also play crucial roles similar to cytokines. The kidneys are highly susceptible to intrinsic oxidative stress resulting from ischemia and to the excessive inflammatory response resulting from systemic autoimmunity. These types of stress may eventually result in the development of acute kidney injury (AKI). In this setting, the skewed cytokine profile produced by macrophages and lymphocytes disrupts the reciprocal relationship for regulating tissue repair and remodeling due to amplification of a physiological vicious loop. We have so far shown that AKI induces the secretion of midkine (MK) and CD147/basigin, which are responsible for skewed cytokine production. MK and CD147/basigin secreted by tubular epithelial cells promote the recruitment of macrophages and neutrophils, respectively, which are accompanied by monocyte chemotactic protein- 1, transforming growth factor-β, E cadherin, and extracellular matrix metalloproteinase inducer. This chapter will present the functions of macrophage-related cytokines and EVs and summarize our findings on how MK and CD147/basigin are involved in the pathogenesis of AKI.

DOI： 10.1007/978-981-15-1108-0_23