title: Erythropoietin and inhibitors of in vitro erythropoiesis in the development of anemia in children with renal disease.
abstract: The relative roles of erythropoietin and potential inhibitors of erythropoiesis in the development of anemia in children with renal disease have been studied. Thirty-five children with renal disease of varied origins and severity were compared with 30 children with anemia of similar severity and with normal renal function. Serum erythropoietin was measured by radioimmunoassay; erythroid (CFU-E) and granulocytic (CFU-GM) progenitor cell growth were assessed in fetal mouse liver cell and normal human bone marrow cell cultures, respectively. The degree of serum inhibition of in vitro CFU-E growth in children with renal disease correlated with both creatinine clearance (r = 0.59, P less than 0.001) and hematocrit level (r = 0.55, P less than 0.005). Serum from children with renal disease inhibited in vitro CFU-E growth in a dose-related manner. Normal serum did not inhibit CFU-E growth in culture. The mean serum erythropoietin concentration was significantly (P less than 0.025) higher in children with anemia of renal disease (32.4 +/- 2.4 mU/ml) in comparison with serum values in normal children (19.6 +/- 1.5 mU/ml), but serum erythropoietin levels did not correlate with hematocrit level, creatinine clearance, or serum inhibition of in vitro erythropoiesis. In contrast, children with anemia and normal renal function showed a significant (P less than 0.001) linear increase in serum erythropoietin concentration (range 28.7 to 327 mU/ml), increased reticulocyte count, and stimulation of CFU-E formation with decreasing hematocrit levels. Coincubation of human urinary erythropoietin in the presence of serum from patients with uremia revealed markedly less immunoreactivity in the radioimmunoassay and less biologic activity in the fetal mouse liver CFU-E assay for erythropoietin than when erythropoietin was incubated with normal human serum, suggesting some alteration of erythropoietin in the presence of uremic serum, which reduced both the immunologic and biologic activity of erythropoietin. Normal and uremic sera inhibited CFU-GM growth to the same degree in comparison with controls. In conclusion, relative erythropoietin deficiency, direct alteration in the biologic activity of erythropoietin by uremic toxins, and serum inhibition of erythroid progenitor cells in the bone marrow are probably important factors in the pathogenesis of anemia in children with renal disease.
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000150:complications*; D000293:Adolescent; D000740:Anemia / Q000097:blood / Q000209:etiology*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003114:Colony-Forming Units Assay; D003404:Creatinine / Q000097:blood; D004920:Erythropoiesis; D004921:Erythropoietin / Q000037:antagonists & inhibitors / Q000097:blood*; D005260:Female; D006400:Hematocrit; D006801:Humans; D008297:Male; D051379:Mice; D011863:Radioimmunoassay; D006435:Renal Dialysis; D013234:Stem Cells / Q000378:metabolism; D014511:Uremia / Q000097:blood
chemical_list: D004921:Erythropoietin; D003404:Creatinine