Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients

Background: Chronic hemolysis, inadequate production of erythropoietin (EPO ) or an impaired response of erythroid stem cells to EPO are the main facto rs of anemia in end-stage renal disease (ESRD) patients. Oxidative damage o f red blood cell (RBC) membrane is a well-established cause of chronic hemo lysis in hemodialysis (HD) patients. Administration of high-dose recombinan t human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients althou gh all established factors of resistance to rHuEPO therapy have been previo usly ruled out or corrected. Patients and methods: We investigated the degr ee of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months c onsecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treat ment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxida tive stress in erythrocyte membrane. Results: No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and d ialysis related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lact ate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of grou ps B and C. Moreover, a significant inverse relationship was observed betwe en RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together. Conclusion: In conclusion, increased oxid ative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established fa ctors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis d ue to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO.