Serum Erythropoietin levels and inhibitors of erythropoiesis in patients with chronic renal failure.

The role of various factors in erythropoiesis was studied in 13 predialysis patients and 41 hemodialysis patients. Serum erythropoietin (ESF) was measured by the fetal mouse liver cell bioassay in vitro. The effect of uremic sera on heme synthesis and erythroid progenitor cell (CFU-E) formation was examined using normal human bone marrow cultures. Serum ESF levels in both predialysis (99.9 +/- 45.0 mU/ml) and dialysis (141.2 +/- 109.7 mU/ml) patients were significantly higher than those in normal controls (42.0 +/- 25.8 mU/ml), although the titers were not sufficiently increased to correct the anemia. Serum ESF concentrations did not correlate with hemoglobin level or inhibition of both heme synthesis and CFU-E formation. Bone marrow CFU-Es in uremic patients were normal in the number, the responsiveness to ESF and the percentage in S-phase. Significant decrease in heme synthesis was observed in dialysis patients. The degree of inhibition of CFU-E formation showed a relationship to hemoglobin levels in uremic patients. By the CFU-E formation assay, the difference in inhibitory effects of the sera obtained from dialysis patients immediately before and after a hemodialysis was significant only under a low ESF concentration (0.125 U/ml) but not under a high concentration (1.0 U/ml). In conclusion, inhibition of heme synthesis and CFU-E formation, in addition to inadequate ESF production, plays an important role in renal anemia.