[Calcitriol increases burst forming unit-erythroid (BFU-E) in vitro proliferation in chronic uremia. Synergic effect with DNA recombinant erythropoietin (rHu-Epo)].
BACKGROUND
It has been suggested that calcitriol (C) could improve anemia in chronic renal failure. However it remains debatable whether vitamin D has a specific effect on erythropoiesis, or it acts via suppression of hyperparathyroidism.


METHODS
We enrolled 29 patients with chronic renal failure, free from malignancies, iron deficiency or other chronic or hematological diseases. Aluminium accumulation was also excluded by DFO test. 22 were on hemodialysis and 7 on conservative management, creatinine clearance ranging 22-48 ml/min. Their mean age was 62+/-28 years and duration of renal disease was 98+/-51 months. No patient under-went rHu-Epo or Vitamin D treatment. 4 subjects were enrolled as controls. Samples of peripheral blood were drawn for the Burst Forming Unit-Erythroid (BFU-E) assay. After isolation of mononuclear cells by density gradient centrifugation with Fycoll-Hypaque, a 15-day incubation was set up with four different conditions: a) adding standard dose, 3 U/ml, of r-HuEpo (Dompè Biotec), standard colture; b) combined doses of r-HuEpo, 3 U/ml, and C (Abbott), 30 pg; c) standard dose, 3 U/ml, of r-HuEpo and high dose, 300 pg, of C; and lastly d) combined high doses of r-HuEpo, 30 U/ml, and C, 300 pg.


RESULTS
In the b colture (combined low doses) a higher BFU-E proliferation was found vs standard (a) colture (33.2+/-15.5 vs 17.1+/-9.2, p<0.02); interestingly, either in the c and d studies BFU-E showed an even higher proliferation (52.3+/-24 and 86.3+/-37.8 respectively, p<0.01 vs a). No difference was found when evaluating separately preterminal and hemodialysis patients. In control subjects only colture d showed an increased BFU-E proliferation.


CONCLUSIONS
C has a direct effect on erythroid precursors proliferation in vitro, acting in a sinergystic manner with rHuEpo. C may be useful as adjuvant therapy for renal anemia.
Aucella
F
F
Divisioni di Nefrologia e Dialisi, Ospedale Casa Sollievo della Sofferenza, IRCCS San Giovanni Rotondo, Foggia, Italy. fauceltin.it
Gatta
G
G
Vigilante
M
M
Scalzulli
R P
RP
Mantuano
S
S
Carotenuto
M
M
Stallone
C
C
D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D002908:Chronic Disease; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects*; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications; D008875:Middle Aged; D011994:Recombinant Proteins; D014511:Uremia / Q000097:blood / Q000209:etiology
D002120:Calcium Channel Agonists; D011994:Recombinant Proteins; D004921:Erythropoietin; D002117:Calcitriol