Hematopoietic inhibitors in chronic renal failure: lack of in vitro specificity.
To assess the potential role of retained inhibitors in the pathogenesis of the anemia of chronic renal failure, we have studied simultaneously the effects of increasing concentrations of normal or uremic sera on the growth of erythroid colonies (from CFU-E), granulocyte-macrophage colonies (from CFU-GM), and megakaryocytic colonies (from CFU-Meg) in mouse marrow cell cultures. As compared to normal human serum, increasing concentrations of uremic sera induced a dose-dependent inhibition in the growth of all colony types. Significant correlations (P less than 0.001) were found between the ability of any individual uremic serum to support CFU-E, CFU-GM, and CFU-Meg growth, and, whenever significant inhibition was seen, all three progenitor types were affected. The inhibitory effect on CFU-E growth was significantly greater (P less than 0.01) in patients with serum creatinine concentrations greater than or equal to 7 mg/dl, but no correlation was found between CFU-E inhibition and hematocrit. Likewise, inhibition of CFU-GM and CFU-Meg growth was not associated with leukopenia or thrombocytopenia, respectively. Sera from patients undergoing chronic intermittent hemodialysis were assayed before and after one hemodialysis session. In each case, the degree of inhibition of CFU-E and CFU-GM growth decreased after hemodialysis, but improvement in CFU-Meg growth was more variable. These data indicate that uremic sera contain dialyzable inhibitors of in vitro hematopoiesis which increase with the severity of renal dysfunction, but these inhibitors lack specificity. If uremic inhibitors of erythropoiesis are of pathophysiologic significance in vivo, there must be unrecognized repair mechanisms for granulopoiesis and thrombopoiesis.
Delwiche
F
F
Segal
G M
GM
Eschbach
J W
JW
Adamson
J W
JW
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004905:Erythrocyte Aging; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006400:Hematocrit; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008222:Lymphokines / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood
D008222:Lymphokines; C022173:stem cell inhibitory factor