EPO responsiveness in hemodialysis patients with excessive ferritin

ESA responsiveness in hemodialysis patients is influenced by various factors such as inflammation, secondary hyperparathyroidism and nutrition. Recently, hepcidin-25, a key regulator of iron homeostasis, was shown to be involved in the pathogenesis of low ESA responsiveness. However, the precise mechanisms of ESA responsiveness remain to be fully elucidated. We examined the relationship between ESA responsiveness and the various clinical parameters of hemodialysis patients with sufficient iron stores (ferritin over 100ng/mL). Twenty-nine hemodialysis patients under epoetin beta (EPO) treatment were divided into two groups, Hb-Low (Hb less than 10g/dL) and Hb-High (Hb more than 10g/dL) groups, and their hematological parameters, the status of iron metabolism and inflammatory markers were compared. Hepcidin-25 and ferritin of the Hb-Low group were significantly higher than those of the Hb-High group (Hb-Low vs. Hb-High, hepcidin-25: 74.7±48.8 vs. 40.1±24.5ng/mL, p=0.018; ferritin: 257±148 vs. 140±61ng/mL, p=0.007). CRP tended to be higher in the Hb-Low group compared to Hb-High group (0.41±0.55 vs. 0.14±0.23mg/dL, respectively, p=0.074), and there was a negative correlation between CRP and Hb in the Hb-Low group. Although the reticulocyte count tended to be higher in the Hb-Low group compared to Hb-High group, this led to no improvement in Hb (Hb: 9.4±0.6 vs. 10.5±0.5g/dL, p<0.001; RET‰: 12.9±4.5 vs. 9.9±4.2‰, p=0.083, respectively). Our data suggest that, in hemodialysis patients presenting with low hemoglobin and sufficient iron stores, high ferritin and a high hepcidin-25 concentration might induce defective iron utilization. In addition, from the tendencies of high CRP and high reticulocytes, a shortened erythrocyte lifespan and micro-inflammation might exist in these patients. The combined impact of these factors may contribute to the low ESA responsiveness.