Influence of volume overload on endogenous erythropoietin production in hemodialysis patients

Background Anemia in hemodialysis patients is primarily attributed to insufficient erythropoietin production. In patients with heart failure-related anemia, erythropoietin production is often inadequate relative to the hemoglobin level. Therefore, we hypothesized that cardiac stress induced by volume overload in hemodialysis patients might influence endogenous erythropoietin production and anemia status. Methods Changes in serum erythropoietin, hemoglobin, total protein, and reticulocyte levels across three consecutive hemodialysis sessions within one week were investigated. All patients were undergoing three times weekly hemodialysis and were not receiving erythropoiesis-stimulating agents or hypoxia-inducible factor prolyl hydroxylase inhibitors. Patients were divided into three groups based on the percentage of body weight gain at the first session of the week, relative to the weight at the end of the previous session (Group A: >5%, n = 11; Group B: 3 − 5%, n = 15; and Group C: <3%, n = 5). Results In Groups A and B, both total protein and hemoglobin levels at the beginning of the second and third sessions were significantly higher than those at the first session, which suggests hemoconcentration due to water removal. However, relative to the level at the beginning of the first session, the serum erythropoietin level at the beginning of the second and third sessions increased more drastically (Group A: 82.5 ± 130.3%, and 99.1 ± 118.8%; Group B: 79.6 ± 130.3%, and 83.0 ± 114.6%, respectively) than the total protein (Group A: 4.9 ± 2.6%, and 5.6 ± 2.9%; Group B: 2.6 ± 4.0%, and 2.5 ± 3.9%, respectively) and hemoglobin levels (Group A: 4.1 ± 3.7%, and 5.5 ± 2.1%; Group B: 3.4 ± 3.3%, and 3.2 ± 4.3%, respectively). Changes in these parameters in Group C were unremarkable, and changes in reticulocyte count were unremarkable across all groups. Conclusion The disproportionate increase in the serum erythropoietin level suggests a stimulation of innate erythropoietin production rather than mere hemoconcentration. Endogenous erythropoietin production is stimulated by the excessive water removal necessary to correct volume overload in hemodialysis patients. Further research is needed to elucidate the underlying mechanisms of this erythropoietin stimulation and its potential influence on hematopoiesis and the patient's anemia status.