Long-Term Erythropoietin Therapy Does Not Affect Metalloproteinases and Their Inhibitor Levels, Oxidative Stress and Inflammation in Hemodialyzed Patients

Abstract

Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in the atherosclerosis. Recombinant human erythropoietin (EPO) has become widely used to treat anemic hemodialyzed (HD) patients; however, an increased mortality has been reported for HD patients with cardiovascular disease when randomly assigned to normal hematocrit by EPO. Therefore, we conducted a study examining the effect of EPO on MMPs/TIMPs system, oxidative stress and inflammation in these patients. Methods: Assessment of MMP-2, MMP-9, TIMP-1 and TIMP-2 were performed in 20 stable HD patients and 15 healthy controls. Additionally, the effects of EPO on malondialdehyde (MDA) – a marker of SOX and C-reactive protein (CRP) levels – as a marker of inflammation were also investigated. Of the 20 patients, 10 were receiving EPO therapy [HD-EPO(+)] for 12 months or more and 10 were not receiving EPO therapy [HD-EPO(–)]. Both groups were not receiving iron supplementation. Results: All parameters, with the exception of MMP-9, were lower in the healthy subjects compared with the HD subjects, irrespective of EPO administration. There was no difference in MMPs/TIMPs system, MDA and C-reactive levels between HD-EPO(+) and HD-EPO(–) patients. Conclusion:Erythropoietin therapy did not influence MMPs/TIMPs system, inflammation, or SOX in a low-risk HD patient population, in the absence of concomitant iron supplementation and mean Hg levels within target.