Cunningham Amy, Kirk Martin, Hong Emily, Yang Jing, Howard Tamara, Brearley Adrian, Sáenz-Trevizo Angelica, Krawchuck Jacob, Watt John, Henderson Ian, Dokladny Karol, DeAguero Joshua, Escobar G Patricia, Wagner Brent
School of Medicine, University of New Mexico Health Science Center, Albuquerque, NM, United States.
Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM, United States.
Front Toxicol. 2024 Aug 12;6:1376587. doi: 10.3389/ftox.2024.1376587. eCollection 2024.
Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. We suspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models.
钆基造影剂在临床实践中的使用越来越广泛。虽然这些药物已被证实是导致肾源性系统性纤维化的病因,但越来越多的文献支持它们在静脉使用后与钆暴露相关症状以及鞘内给药后脑病中作为病因的作用。钆基造影剂是多齿有机配体,能强烈结合金属离子以降低金属的毒性。阳离子钆从这些螯合物中解离并引发疾病的观点在患者和医疗人员中很普遍。我们假设患者体内未与配体结合的(可溶性)钆含量极低。可溶性离子钆不太可能是介导任何疾病的初始步骤。新墨西哥肾脏研究所率先在啮齿动物磁共振成像造影剂的皮肤和肾脏组织中发现了富含钆的纳米颗粒。2023年,他们在肾功能正常的人类肾脏细胞中发现了类似的纳米颗粒,可能来自造影剂。我们怀疑这些纳米颗粒是磁共振成像造影剂慢性毒性的介质。本文探讨了钆造影剂与临床报告和啮齿动物模型所支持的不良健康结果之间的关联。