Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy

Key Points. IgA nephropathy often requires KRT. Mesenchymal stem cells offer clinical benefits. Adipose-derived mesenchymal stem cells are safe and tolerable. Background. IgA nephropathy (IgAN) often requires KRT because of its refractoriness and because corticosteroids pose infection risks. However...

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Main Authors: Akihito Tanaka, Kazuhiro Furuhashi, Kumiko Fujieda, Asuka Horinouchi, Kayaho Maeda, Shoji Saito, Tetsushi Mimura, Yosuke Saka, Tomohiko Naruse, Takuji Ishimoto, Noritoshi Kato, Tomoki Kosugi, Fumie Kinoshita, Yachiyo Kuwatsuka, Yasuhiro Nakai, Shoichi Maruyama
Format: Article
Language:English
Published: Wolters Kluwer - Lippincott Williams & Wilkins 2024-11-01
Series:Kidney360
Online Access:http://journals.lww.com/10.34067/KID.0000000000000563
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author Akihito Tanaka
Kazuhiro Furuhashi
Kumiko Fujieda
Asuka Horinouchi
Kayaho Maeda
Shoji Saito
Tetsushi Mimura
Yosuke Saka
Tomohiko Naruse
Takuji Ishimoto
Noritoshi Kato
Tomoki Kosugi
Fumie Kinoshita
Yachiyo Kuwatsuka
Yasuhiro Nakai
Shoichi Maruyama
author_facet Akihito Tanaka
Kazuhiro Furuhashi
Kumiko Fujieda
Asuka Horinouchi
Kayaho Maeda
Shoji Saito
Tetsushi Mimura
Yosuke Saka
Tomohiko Naruse
Takuji Ishimoto
Noritoshi Kato
Tomoki Kosugi
Fumie Kinoshita
Yachiyo Kuwatsuka
Yasuhiro Nakai
Shoichi Maruyama
author_sort Akihito Tanaka
collection DOAJ
description Key Points. IgA nephropathy often requires KRT. Mesenchymal stem cells offer clinical benefits. Adipose-derived mesenchymal stem cells are safe and tolerable. Background. IgA nephropathy (IgAN) often requires KRT because of its refractoriness and because corticosteroids pose infection risks. However, mesenchymal stem cells offer clinical benefits because of their regenerative and immunomodulatory properties. This prospective clinical trial assessed the safety and tolerability of adipose-derived mesenchymal stem cell (ASC) therapy and evaluated its therapeutic efficacy. Methods. This phase 1 study included adult patients with refractory IgAN that was difficult to treat with traditional therapies. ASC therapy comprising one intravenous dose of 1×108 cells was administered to three to six patients in Cohort 1. The same intravenous dose was administered twice with a 2-week interval to six patients in Cohort 2. Heparin was administered simultaneously. This study continued for 52 weeks, and the primary end points were safety and tolerability during the 6-week period after treatment administration. Secondary end points included adverse events and efficacy measures such as clinical remission, partial remission, urine protein remission, hematuria remission, time to remission, changes in the urine protein and hematuria levels, and changes in the eGFR. Results. The three patients in Cohort 1 and six patients in Cohort 2 who received ASC therapy achieved the primary end points. No severe adverse clinical events were observed. Therefore, the safety and tolerability of ASCs were confirmed. Improvements, such as significantly decreased kidney damage markers and urinary protein levels, were observed immediately after ASC administration. Conclusions. The safety and tolerability of ASCs are acceptable for patients with IgAN. Clinical Trial registry name and registration number:. This trial was registered with the Japan Registry of Clinical Trials (jRCT2043200002; registration date: April 14, 2020) and ClinicalTrials.gov (NCT04342325; registration date: April 13, 2020).
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spelling doaj-art-a3527ea28acf4ffeae97ec70095ad48d2025-08-20T02:47:13ZengWolters Kluwer - Lippincott Williams & WilkinsKidney3602641-76502024-11-015111692170510.34067/KID.0000000000000563202411000-00013Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA NephropathyAkihito Tanaka0Kazuhiro Furuhashi1Kumiko Fujieda2Asuka Horinouchi3Kayaho Maeda4Shoji Saito5Tetsushi Mimura6Yosuke Saka7Tomohiko Naruse8Takuji Ishimoto9Noritoshi Kato10Tomoki Kosugi11Fumie Kinoshita12Yachiyo Kuwatsuka13Yasuhiro Nakai14Shoichi Maruyama151 Department of Nephrology, Nagoya University Hospital, Nagoya, Japan1 Department of Nephrology, Nagoya University Hospital, Nagoya, Japan1 Department of Nephrology, Nagoya University Hospital, Nagoya, Japan2 Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan2 Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan1 Department of Nephrology, Nagoya University Hospital, Nagoya, Japan3 Department of Nephrology, Kasugai Municipal Hospital, Kasugai, Japan3 Department of Nephrology, Kasugai Municipal Hospital, Kasugai, Japan3 Department of Nephrology, Kasugai Municipal Hospital, Kasugai, Japan4 Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute, Japan2 Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan2 Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan5 Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan5 Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan5 Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan2 Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, JapanKey Points. IgA nephropathy often requires KRT. Mesenchymal stem cells offer clinical benefits. Adipose-derived mesenchymal stem cells are safe and tolerable. Background. IgA nephropathy (IgAN) often requires KRT because of its refractoriness and because corticosteroids pose infection risks. However, mesenchymal stem cells offer clinical benefits because of their regenerative and immunomodulatory properties. This prospective clinical trial assessed the safety and tolerability of adipose-derived mesenchymal stem cell (ASC) therapy and evaluated its therapeutic efficacy. Methods. This phase 1 study included adult patients with refractory IgAN that was difficult to treat with traditional therapies. ASC therapy comprising one intravenous dose of 1×108 cells was administered to three to six patients in Cohort 1. The same intravenous dose was administered twice with a 2-week interval to six patients in Cohort 2. Heparin was administered simultaneously. This study continued for 52 weeks, and the primary end points were safety and tolerability during the 6-week period after treatment administration. Secondary end points included adverse events and efficacy measures such as clinical remission, partial remission, urine protein remission, hematuria remission, time to remission, changes in the urine protein and hematuria levels, and changes in the eGFR. Results. The three patients in Cohort 1 and six patients in Cohort 2 who received ASC therapy achieved the primary end points. No severe adverse clinical events were observed. Therefore, the safety and tolerability of ASCs were confirmed. Improvements, such as significantly decreased kidney damage markers and urinary protein levels, were observed immediately after ASC administration. Conclusions. The safety and tolerability of ASCs are acceptable for patients with IgAN. Clinical Trial registry name and registration number:. This trial was registered with the Japan Registry of Clinical Trials (jRCT2043200002; registration date: April 14, 2020) and ClinicalTrials.gov (NCT04342325; registration date: April 13, 2020).http://journals.lww.com/10.34067/KID.0000000000000563
spellingShingle Akihito Tanaka
Kazuhiro Furuhashi
Kumiko Fujieda
Asuka Horinouchi
Kayaho Maeda
Shoji Saito
Tetsushi Mimura
Yosuke Saka
Tomohiko Naruse
Takuji Ishimoto
Noritoshi Kato
Tomoki Kosugi
Fumie Kinoshita
Yachiyo Kuwatsuka
Yasuhiro Nakai
Shoichi Maruyama
Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy
Kidney360
title Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy
title_full Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy
title_fullStr Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy
title_full_unstemmed Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy
title_short Safety and Tolerability of Adipose-Derived Mesenchymal Stem Cell (ADR-001) Therapy for IgA Nephropathy
title_sort safety and tolerability of adipose derived mesenchymal stem cell adr 001 therapy for iga nephropathy
url http://journals.lww.com/10.34067/KID.0000000000000563
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