Erythropoiesis-stimulating agent withdrawal and oxidative stress in hemodialysis

Abstract

Aims: Variation of the action of erythropoiesis-stimulating agent (ESA) may modify oxidative stress in hemodialyzed (HD) patients. Our aim was to follow changes of oxidative stress during withdrawal and subsequent resumption of ESA therapy.

Patients and methods: After a 14-day suspension of epoietin-beta treatment, 11 HD patients received epoietin-beta and 10 patients darbepoietin-alpha. The whole blood oxidized and reduced glutathione (GSSG, GSH) and erythrocyte malondialdehyde (E-MDA) concentrations and the erythrocyte superoxide dismutase (E-SOD) and catalase (E-CAT) activities were determined before the ESA-free interval (baseline) and at Weeks 2, 6, 10 and 14.

Results: In both groups, the ratios GSSG/ GSH were increased at Weeks 2 and 6 (p < 0.001). The E-MDA levels were elevated (p < 0.01) and the E-SOD activities were decreased (p < 0.001) at Week 6. By Week 14, these markers had returned to the baseline, whereas the GSH (p < 0.001) and E-CAT activity levels (p < 0.001) had increased.

Conclusions: An increase in oxidative stress was revealed by the ratio GSSG/GSH directly after the short-term withdrawal of epoietin-b therapy in HD. This new finding may have implications in conditions involving transiently depressed ESA action. For both ESAs, the early phase of readministration was associated with similarly increased oxidative stress, with a subsequent return to the baseline level.