Modulation of platelet cytosolic calcium during erythropoietin therapy in uraemia.
Erythropoietin therapy for uraemic anaemia is associated with a high rate of hypertensive and thrombotic complications. The mechanism is unknown, but a change in cellular calcium control may be relevant to changes in blood pressure and thrombosis. Platelets were utilized as a model of vascular smooth muscle cells. The effects of erythropoietin therapy on platelet cellular calcium, assessed by fura-2, were measured in 25 patients receiving renal replacement therapy during a 6-month treatment period. Three patients failed to reach a target haemoglobin and were excluded from the analysis. Blood pressure increased in 11 of the remaining 22 subjects, eight requiring an increase in antihypertensive medication. There were no differences in cellular calcium control between the group in whom blood pressure rose and patients with stable blood pressure. Overall there was a fall of 24% in resting cytosolic calcium (baseline 69.2 +/- 5.1 to 52.5 +/- 3.0 nmol/l, P < 0.05) after 3 months of erythropoietin therapy. There was no change in the thrombin-stimulated peak response in the presence of extracellular calcium during therapy, although thrombin-stimulated intracellular release also fell at 3 months (baseline 769 +/- 61 versus 3 months 559 +/- 49 nmol/l, P < 0.01). This study suggests that intracellular free calcium control within platelets improves in response to erythropoietin therapy. However these changes appear not to be related to the development of hypertension.
Fluck
R J
RJ
Department of Nephrology, Royal Hospital of St Bartholomew, London, UK.
Roger
S D
SD
McMahon
A C
AC
Raine
A E
AE
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000097:blood*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004921:Erythropoietin / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced; D014511:Uremia / Q000097:blood* / Q000150:complications / Q000188:drug therapy*
D011994:Recombinant Proteins; D004921:Erythropoietin; D002118:Calcium