Association of Selenium with Response to Erythropoiesis-Stimulating Agents in Elderly Patients

Background: Poor response to erythropoiesis-stimulating agents (ESAs) is associated with increased mortality and cardiovascular events in hemodialysis patients. Managing ESA hyporesponsiveness is essential to optimize treatment. Contributing factors include iron deficiency, prolonged dialysis, malnutrition, inflammation, and possibly trace elements. Selenium (Se) is a trace element essential for many biological functions. We previously reported that low serum Se (<10.5 μg/dL) is common in dialysis patients and correlates with decreased ESA responsiveness (Yasukawa et al. Kidney Int Rep 2022). Given the increasing age of dialysis populations, we examined factors associated with ESA hyporesponsiveness in older patients. Methods: Among 173 patients with measured serum Se, 145 on ESAs were analyzed. Data were collected from medical records. ESA resistance index (ERI) was calculated as described previously. Serum Se levels were measured using ICP-MS. Cross-sectional analysis was performed to assess associations between ERI and clinical parameters, including Se. Results: Among 145 patients, 51 were aged ≥75 (older group) and 94 were <75 (younger group). In younger patients, multivariable analysis showed that female gender, longer dialysis duration, low TSAT, and low Se were significantly associated with increased ERI. In older patients, female gender, low TSAT, and low Se were also associated with higher ERI, but dialysis duration was not. The inverse relationship between Se and ERI in older patients remained significant after adjusting for albumin, cardiovascular disease, and diabetes. Conclusion: Although factors associated with ESA hyporesponsiveness may differ by age, our study suggests that low serum Se is consistently associated with ESA hyporesponsiveness in both older and younger patients. These findings underscore the role of selenium in anemia management.