Short- and long-term effects of erythropoietin treatment on endothelial progenitor cell levels in patients with cardiorenal syndrome.
OBJECTIVE
Patients with cardiorenal syndrome (CRS) have high cardiovascular morbidity. Endothelial progenitor cells (EPC) constitute an endogenous vascular repairsystem, protecting against atherosclerosis development. Erythropoietin (EPO) treatment may have beneficial effects by mobilizing EPC from the bonemarrow. Our objective is to determine EPC levels and effects of EPO therapy on EPC levels in CRS patients.


METHODS
Open-label randomized trial.


METHODS
Part of the EPOCARES-trial, conducted in Utrecht (Netherlands).


METHODS
Patients with CRS and anaemia and healthy controls were included. Interventions Patients were randomized to receive EPO therapy (50 IU/kg/wk) for 52 weeks or no EPO therapy.


METHODS
CD34(+)KDR(+)-EPC, cultured EPC outgrowth and function at baseline, after 18 days and after 52 weeks.


RESULTS
Patients showed lower CD34(+)KDR(+)-cell numbers compared to controls (6(12) vs. 19(19) cells/10(5) granulocytes; p = 0.010), despite increased levels of stromal cell-derived factor-1α; (3.1(0.8) vs 2.6(0.3) ng/ml; p = 0.001). EPC outgrowth and function were not different between patients and controls. EPC levels did not change after 18&emsp14;days with or without EPO treatment. CD34(+)KDR(+)-cells significantly declined after 52 weeks in the non-treated group (p = 0.028). Long-term EPO therapy did not significantly affect this reduction in CD34(+)KDR(+)-EPC levels.


CONCLUSIONS
CRS patients showed reduced CD34(+)KDR(+)-EPC levels compared to controls, consistent with a reduced vascular regenerative potential and despite upregulated SDF-1α levels. Over a one-year follow-up period a marked 68% further reduction in EPC levels was observed in the patient group without EPO treatment. In spite of promising experimental studies, our longitudinal, randomized study did not show significant influence of either short- or long-term EPO therapy on reduced EPC levels in CRS patients.
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands.
Kim E
KE
Jie
Karien
K
van der Putten
Marloes W T
MW
Bergevoet
Pieter A
PA
Doevendans
Carlo A J M
CA
Gaillard
Branko
B
Braam
Marianne C
MC
Verhaar
D000740:Anemia / Q000188:drug therapy*; D018952:Antigens, CD34 / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008134:Long-Term Care; D008297:Male; D011994:Recombinant Proteins; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology; D013577:Syndrome
D018952:Antigens, CD34; D054377:Chemokine CXCL12; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin