維持血液透析患者におけるエリスロポエチン活性 ： 第2報 CFU-E由来コロニー形成能に対するポリアミンの影響

Abstract

It has been thought that the pathogenesis of anemia in patients with chronic renal failure may be largely due to erythropoietin (EPO) deficiency. But recently there have been reports that uremic inhibitors may suppress the activity of EPO and reduce the maturation of erythropoiesis. Polyamine is well known to be involved in the regulation of cellular proliferation and differentiation. The serum levels of polyamine are elevated in chronic hemodialytic patients, and lowered immediately by hemodialysis. In this study the author first measured polyamine level (putrescine, spermidine, spermine) by high performance liquid chromatography (HPLC) in 20 chronic hemodialytic patients, and investigated the effect of polyamine on the erythropoiesis. Secondly, each polyamine is added directly to the medium of fetal mouse liver cell culture plates in order to comfirm the direct inhibitory effect on the growth of CFU-E in the presence of recombinant human EPO (r-huEPO). Each polyamine level in chronic hemodialytic patients was higher than normal, and there was significant negative correlation between polyamine and erythropoietic activity designed by CFU-E/log EPO. In the in vitro study, the growth of CFU-E under r-huEPO was substantially suppressed by polyamine in the manner of dose response. These results suggest the conclusion that polyamine had an inhibitory effect on the proliferation or maturation of erythroid precursor cells and was intimately involved in the pathogenesis of the anemia in chronic hemodialytic patients. However further study should be done for full interpretation of its clinical importance in anemia associated with hemodialytic patient.