P0847HEPATIC ERYTHROPOIETIN SYNTHESIS IS ENHANCED IN HEMODIALYSIS PATIENTS WHO DO NOT REQUIRE ERYTHROPOIESIS-STIMULATING AGENTS

Abstract

Abstract Background and Aims Erythropoietin is synthesized in the liver during the fetal period and mainly in the kidney after birth. However, some patients with end-stage chronic kidney disease do not require the administration of erythropoiesis-stimulating agents (ESA) despite their damaged renal function. This study aimed to clarify the origin of extrarenal erythropoietin generation in these patients. Method The origin of erythropoietin was investigated by analyzing the erythropoietin glycation patterns based on the percentages of migrated isoforms (PMI). Sera of stable hemodialysis (HD) patients with (ESA group) or without (non-ESA group) ESA treatment and umbilical cord blood of newborns (UCB group), which contained erythropoietin of liver origin, were analyzed. The non-ESA group was determined as HD patients without ESA treatment for > 6 months. Informed consent was obtained from all included HD patients and from the parents or guardians of the newborns. This study was performed with permission from the institutional ethical committee and was registered as a clinical trial (no. R000033462 UMIN000029335). Results The mean duration of no ESA treatment in the non-ESA group was 29.2 months. There were no differences in major clinical parameters, including age and HD duration. The hemoglobin concentration in the ESA group was 107 ± 5 g/L (mean ± standard error), which was significantly lower than that in the non-ESA group (123 ± 4 g/L) (P = 0.025, unpaired Student’s t-test). The PMI values of the ESA, non-ESA, and UCB groups were 12.6 ± 11.4％, 61.2 ± 13.1%, and 65.0 ± 13.5％, respectively, and the PMI value of the ESA group was significantly lower than that of non-ESA or UCB group (one-way analysis of variance with Tukey-Kramer test), suggesting that the glycation pattern of erythropoietin in the non-ESA group was similar to that in the UCB group but different from that in the ESA group. No significant differences were found in the reticulocyte ratio, serum iron concentration, total iron binding capacity, and ferritin and transferrin saturation between the ESA and non-ESA groups. Conclusion These results suggest that patients in the non-ESA group had enhanced extrarenal erythropoietin synthesis and that their erythropoietin originated from the liver. Further analysis of the underlying mechanism may contribute to the development of internal extrarenal erythropoietin-stimulating therapy.