Yasukawa Minoru, Arai Shigeyuki, Nagura Michito, Kido Ryo, Asakawa Shinichiro, Hirohama Daigoro, Yamazaki Osamu, Tamura Yoshifuru, Fujimaki Michitaka, Kobayashi Sawako, Mimaki Masakazu, Kodama Hiroko, Uchida Shunya, Fujigaki Yoshihide, Shibata Shigeru
Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Medical Checkup Center, Inagi Municipal Hospital, Tokyo, Japan.
Kidney Int Rep. 2022 Apr 16;7(7):1565-1574. doi: 10.1016/j.ekir.2022.04.009. eCollection 2022 Jul.
Impaired response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality in patients with end-stage kidney disease. However, the underlying mechanisms are not fully elucidated. Accumulating data reveal that selenium (Se), a trace element, plays a key role in stress erythropoiesis and erythrocyte homeostasis. We evaluated the relationship between serum Se levels and the response to ESAs in hemodialysis patients.
In this cross-sectional study, we determined serum Se levels in 173 hemodialysis patients. We analyzed the association of serum Se with ESA responsiveness, as defined by ESA resistance index.
Of the study participants, 50% had lower Se levels than the population-based reference values. We found that serum Se levels were significantly and inversely correlated with erythropoiesis resistance index (ERI) but not transferrin saturation (TSAT) or ferritin levels. Multiple regression analyses confirmed the association between Se levels and ESA hyporesponsiveness, independently of other known factors, such as iron status, being female, and dialysis vintage (β = -0.11, < 0.001). When patients were divided according to Se levels and iron status, both low serum Se (<10.5 μg/dl) and iron deficiency significantly affected the response to ESA. Conversely, serum Se levels were significantly different among groups when patients were divided according to ERI quartiles. The association of low serum Se with ESA hyporesponsiveness persisted after adjustment of confounding variables.
Serum Se levels are associated with the response to ESAs and can predict ESA resistance independently of iron status in Japanese hemodialysis patients. These data open the possibility to test whether Se supplementation reduces ESA demand.
促红细胞生成素（ESA）反应受损与终末期肾病患者死亡率增加相关。然而，其潜在机制尚未完全阐明。越来越多的数据表明，微量元素硒（Se）在应激性红细胞生成和红细胞内环境稳定中起关键作用。我们评估了血液透析患者血清硒水平与对ESA反应之间的关系。
在这项横断面研究中，我们测定了173例血液透析患者的血清硒水平。我们分析了血清硒与ESA反应性的相关性，ESA反应性由ESA抵抗指数定义。
在研究参与者中，50%的人硒水平低于基于人群的参考值。我们发现血清硒水平与红细胞生成抵抗指数（ERI）显著负相关，但与转铁蛋白饱和度（TSAT）或铁蛋白水平无关。多元回归分析证实了硒水平与ESA低反应性之间的关联，独立于其他已知因素，如铁状态、女性性别和透析龄（β = -0.11，< 0.001）。当根据硒水平和铁状态对患者进行分组时，低血清硒（<10.5 μg/dl）和缺铁均显著影响对ESA的反应。相反，当根据ERI四分位数对患者进行分组时，各组之间血清硒水平存在显著差异。调整混杂变量后，低血清硒与ESA低反应性之间的关联仍然存在。
血清硒水平与对ESA的反应相关，并且在日本血液透析患者中可独立于铁状态预测ESA抵抗。这些数据为测试补充硒是否可降低ESA需求提供了可能性。
