Bone marrow erythroid precursor Ca++ regulates the response to human recombinant erythropoietin (rHuEPO) in hemodialysis patients.
The modulation of erythropoiesis by erythropoietin is conditioned by the concentration of Ca++ in the cytoplasm of the bone marrow erythroid precursors. We evaluated in vitro erythroid colony development from bone marrow erythroid precursors incubated with increasing concentrations of Ca++ or Ca++ plus 1,25 (OH)2 D3, and bone marrow erythroid precursor cytoplasmic Ca++ concentrations in 10 anemic hemodialysis (HD) patients before and during rHuEPO therapy. Results showed that: a) in vitro: in uremics patients before rHuEPO therapy, bone marrow erythroid precursor cytoplasmic Ca++ was lower than in normal subjects; the addition of Ca++ to the bone marrow erythroid precursors induced a dose-dependent Ca++ and erythroid colony development increase; 1,25 (OH)2 D3 potentiated this effect; b) in vivo: rHuEPO normalized bone marrow erythroid precursor Ca++ and erythroid colony development. An inverse correlation was seen between bone marrow erythroid colony development, precursor CA++ before therapy, the in vitro erythroid and the rHuEPO dose needed in vivo to normalize hematological parameters. These data emphasize the role of Ca++ in erythropoiesis and may aid understanding of the mode of action of rHuEPO in HD.
Carozzi
S
S
Nephrology and Dialysis Unit, St. Paul's Hospital, Savona, Italy.
Ramello
A
A
Nasini
M G
MG
Schelotto
C
C
Caviglia
P M
PM
Cantaluppi
A
A
Salit
M
M
Lamperi
S
S
D000328:Adult; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins; D006435:Renal Dialysis
D011994:Recombinant Proteins; D004921:Erythropoietin; D002118:Calcium