Effect of Erythropoiesis-Stimulating Agent Types on Hemoglobin Variability in Hemodialysis Patients

Background: Our study aimed to evaluate the differences in hemoglobin variability among patients undergoing hemodialysis (HD) treated with three types of erythropoiesis-stimulating agents (ESAs) and the association between hemoglobin variability and clinical outcomes. Methods: In this study, data from the 6th and 7th HD quality assessments were used, comprising 48,726 patients in South Korea. ESAs are categorized into short-acting (epoetin alfa/beta/delta, requiring more frequent administration), intermediate-acting (darbepoetin alfa), and long-acting agents (methoxy polyethylene glycol-epoetin beta, requiring extended dosing intervals), each with distinct pharmacokinetic properties and dosing schedules. Based on use of ESA types, participants were divided into the following groups: Short, Intermediate, and Long. Hemoglobin levels were measured monthly over a 6-month assessment period. Hemoglobin variability was defined as the residual standard deviation derived from a within-subject linear regression model with six hemoglobin values for each patient. Results: The Short, Intermediate, and Long groups comprised 36,420, 10,514, and 1792 patients, respectively. The hemoglobin variability (mean [95% confidence interval]) was 0.60 (0.60-0.60), 0.68 (0.67-0.68), and 0.64 (0.62-0.65) g/dL in the Short, Intermediate, and Long groups, respectively. Multivariate and subgroup analyses revealed that the hemoglobin variability was lower in the Short group than in the other two groups. Cox regression did not show a significant association between an increase in hemoglobin variability and all-cause mortality or cardiovascular events in univariate and multivariate analyses. Conclusions: Our cohort study found that the use of short-acting ESAs showed the lowest hemoglobin variability, whereas the use of intermediate-acting ESAs showed the highest variability. In the context of South Korea's healthcare system, where frequent hemoglobin monitoring and strict ranges are emphasized, short-acting ESAs combined with regular laboratory follow-up appeared to support more stable hemoglobin levels.