Tanaka Akihito, Furuhashi Kazuhiro, Fujieda Kumiko, Horinouchi Asuka, Maeda Kayaho, Saito Shoji, Mimura Tetsushi, Saka Yosuke, Naruse Tomohiko, Ishimoto Takuji, Kato Noritoshi, Kosugi Tomoki, Kinoshita Fumie, Kuwatsuka Yachiyo, Nakai Yasuhiro, Maruyama Shoichi
Department of Nephrology, Nagoya University Hospital, Nagoya, Japan.
Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kidney360. 2024 Nov 1;5(11):1692-1705. doi: 10.34067/KID.0000000000000563. Epub 2024 Aug 26.
IgA nephropathy often requires KRT. Mesenchymal stem cells offer clinical benefits. Adipose-derived mesenchymal stem cells are safe and tolerable.
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.
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 1×10 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.
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.
The safety and tolerability of ASCs are acceptable for patients with IgAN.
: 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).
IgA肾病常需要肾脏替代治疗。间充质干细胞具有临床益处。脂肪来源的间充质干细胞安全且耐受性良好。
IgA肾病（IgAN）因其难治性以及皮质类固醇带来感染风险，常需要肾脏替代治疗。然而，间充质干细胞因其再生和免疫调节特性而具有临床益处。这项前瞻性临床试验评估了脂肪来源的间充质干细胞（ASC）治疗的安全性和耐受性，并评估了其治疗效果。
这项1期研究纳入了难治性IgAN成年患者，这些患者难以用传统疗法治疗。队列1中的3至6名患者接受了包含一次静脉注射1×10个细胞的ASC治疗。队列2中的6名患者以2周的间隔静脉注射相同剂量两次。同时给予肝素。本研究持续52周，主要终点是治疗给药后6周期间的安全性和耐受性。次要终点包括不良事件和疗效指标，如临床缓解、部分缓解、尿蛋白缓解、血尿缓解、缓解时间、尿蛋白和血尿水平的变化以及估算肾小球滤过率（eGFR）的变化。
接受ASC治疗的队列1中的3名患者和队列2中的6名患者达到了主要终点。未观察到严重不良临床事件。因此，证实了ASC的安全性和耐受性。在ASC给药后立即观察到改善，如肾脏损伤标志物和尿蛋白水平显著降低。
ASC的安全性和耐受性对于IgAN患者是可接受的。
本试验在日本临床试验注册中心（jRCT2043200002；注册日期：2020年4月14日）和美国国立医学图书馆临床试验数据库（ClinicalTrials.gov，NCT04342325；注册日期：2020年4月13日）注册。
