Epoetin-alpha: Preserving kidney function via attenuation of polymorphonuclear leukocyte priming

Background: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidneys disease. Eythropoietin-receptor is present on PMNLs. Objectives: 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. EOP-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomecular filtration rate. Results: 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.