Epoetin-alpha: preserving kidney function via attenuation of polymorphonuclear leukocyte priming.
BACKGROUND
Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs. OBJECTIVESxi: To evaluate the effect of 20 weeks of epoetin-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.


METHODS
Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate. esults: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC and PMNL counts and ALP activity following treatment. EPO retarded the deterioration in GFR. The percent of PMNLs expressing EPO-R was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.


CONCLUSIONS
These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.
Department of Nephrology and Hypertension, Western Galilee Hospital, Nahariya, Israel. batya.kristal@naharia.health.gov.il
Batya
B
Kristal
Revital
R
Shurtz-Swirski
Olga
O
Tanhilevski
Galina
G
Shapiro
Galina
G
Shkolnik
Judith
J
Chezar
Tamara
T
Snitkovsky
Meital
M
Cohen-Mazor
Shifra
S
Sela
D000368:Aged; D000740:Anemia / Q000150:complications / Q000188:drug therapy; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006397:Hematinics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017467:Receptors, Erythropoietin / Q000187:drug effects; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism
D006397:Hematinics; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D013482:Superoxide Dismutase