Czaya Brian, Olivera Joseph D, Zhang Moya, Lundin Amber, Castro Christian D, Jung Grace, Nemeth Elizabeta, Ganz Tomas
Center for Iron Disorders, Department of Medicine, David Geffen School of Medicine at UCLA Los Angeles, CA 90095-1690.
bioRxiv. 2024 Dec 10:2024.12.06.627111. doi: 10.1101/2024.12.06.627111.
Anemia is a common and disabling complication of chronic kidney disease (CKD). Current therapies can be burdensome, and full correction of anemia is limited by cardiovascular side effects. New approaches that may offer additional therapeutic options are needed. We explored the anti-anemic effects of erythroferrone, an erythroid hormone that induces iron mobilization by suppressing the master iron-regulatory hormone hepcidin. In a preclinical murine model of adenine-induced CKD, transgenic augmentation of erythroferrone mobilized iron, increased hemoglobin concentrations by approximately 2 g/dl, and modestly improved renal function without affecting systemic or renal inflammation, fibrosis, or markers of mineral metabolism. This study supports the concept that therapeutic augmentation of erythroferrone is a promising approach for alleviating CKD-associated anemia.
贫血是慢性肾脏病(CKD)常见且导致功能障碍的并发症。目前的治疗方法可能很繁琐,而且贫血的完全纠正受到心血管副作用的限制。需要有能提供更多治疗选择的新方法。我们探究了促红细胞生成素铁的抗贫血作用,促红细胞生成素铁是一种红系激素,可通过抑制主要的铁调节激素铁调素来诱导铁动员。在腺嘌呤诱导的CKD临床前小鼠模型中,促红细胞生成素铁的转基因增强作用可动员铁,使血红蛋白浓度增加约2 g/dl,并适度改善肾功能,而不影响全身或肾脏炎症、纤维化或矿物质代谢标志物。这项研究支持了促红细胞生成素铁的治疗性增强是缓解CKD相关性贫血的一种有前景的方法这一概念。