Botelho Bruno Freire, Barreira André Luis, Filippo Marcio Gomes, Asensi Karina Dutra, Faccioli Lanuza A P, Dos Santos Salgado Anna Beatriz, de Salles Elizabeth Figueiredo, Marques Carlos Eduardo Cruz, Silva Pedro Leme, Dos Santos Goldenberg Regina Coeli, Maiolino Angelo, Gutfilen Bianca, de Souza Sergio Augusto Lopes, Junior Maurilo Leite, Morales Marcelo Marcos
Department of Nephrology Clementino Fraga Filho University Hospital Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Vascular Surgery Clementino Fraga Filho University Hospital Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Stem Cells Int. 2024 Jul 9;2024:2385568. doi: 10.1155/2024/2385568. eCollection 2024.
Patients with focal segmental glomerulosclerosis (FSGS) who are refractory to drug treatment may present progressive loss of kidney function, leading to chronic kidney disease stage 5 under dialysis treatment. The safety of systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has been shown in different preclinical models of kidney diseases. However, to date, no study has evaluated the safety and biodistribution of BMDMCs after infusion in renal arteries in patients with FSGS. We used a prospective, non-randomized, single-center longitudinal design to investigate this approach. Five patients with refractory FSGS and an estimated glomerular filtration rate (eGFR) between 20 and 40 ml/min/1.73 m underwent bone marrow aspiration and received an arterial infusion of autologous BMDMCs (5 × 10) for each kidney. In addition, BMDMCs labeled with technetium-99m (Tc-BMDMCs) were used to assess the biodistribution by scintigraphy. All patients completed the 270-day follow-up protocol with no serious adverse events. A transient increase in creatinine was observed after the cell therapy, with improvement on day 30. Tc-BMDMCs were detected in both kidneys and counts were higher after 2 hr compared with 24 hr. The arterial infusion of BMDMCs in both kidneys of patients with FSGS was considered safe with stable eGFR at the end of follow-up. This trial is registered with NCT02693366.
对药物治疗无效的局灶节段性肾小球硬化（FSGS）患者可能会出现肾功能进行性丧失，最终在透析治疗下发展为慢性肾脏病5期。骨髓来源的单个核细胞（BMDMCs）全身给药的安全性已在不同的肾脏疾病临床前模型中得到证实。然而，迄今为止，尚无研究评估FSGS患者肾动脉输注BMDMCs后的安全性和生物分布情况。我们采用前瞻性、非随机、单中心纵向设计来研究这种方法。5例难治性FSGS患者，估计肾小球滤过率（eGFR）在20至40 ml/min/1.73 m²之间，接受了骨髓穿刺，并对每个肾脏进行了自体BMDMCs（5×10⁶）的动脉输注。此外，用锝-99m标记的BMDMCs（Tc-BMDMCs）通过闪烁扫描来评估生物分布。所有患者均完成了270天的随访方案，未出现严重不良事件。细胞治疗后观察到肌酐短暂升高，在第30天有所改善。在两个肾脏中均检测到Tc-BMDMCs，且2小时后的计数高于24小时后的计数。FSGS患者双肾动脉输注BMDMCs被认为是安全的，随访结束时eGFR稳定。该试验已在NCT02693366注册。
