Effect of High Concentration of Uremic Toxin on Erythropoiesis in Acute Blood Loss

Abstract

During advanced renal failure, and particularly in patients with end-stage renal diseases (ESRD), proteins are carbamylated and lose biological activity as the result of a reaction with cyanate which is derived from urea. The effect of cyanate on the erythropoietic activity of erythropoietin (EPO) after acute blood loss in rats was studied. EPO was incubated with cyanate at 37℃. The erythrocytes count, hemoglobin concentration, hematocrit and leukocytes were measured after the subcutaneous injection of either normal saline, cyanate, EPO, or incubated EPO with cyanate. Normal saline or 1 M cyanate injected controls and the incubated EPO with cyanate injected animals demonstrated decrease from day zero in erythropoietic parameters. The parameters maintained in EPO injected group. These results support that EPO exposed to cyanate in vitro demonstrates diminished biologic activity in acute blood loss. This effect suggest that EPO is inhibited in the presence of cyanate under the stimulatory condition for EPO, and it may contribute to the suboptimal erythropoietic response to EPO therapy associated with high urea levels, especially related to inadequate dialysis.