Among patients with end stage renal disease (ESRD), anemia increases the rate of mortality, and low hemoglobin (Hb) levels contribute to an increased rate of hospitalization and shortened survival.The prevalence of left ventricular hypertrophy (LVH) increases as chronic renal progresses and anemia worsens. In fact, as many as 45% of chronic Renal Dieses patients with Hb levels of < 11.4 g/dl manifest LVH [1] .The clinically ideal threshold Hb for the initiation of erythropoietic agents in , early chronic Renal has still not been established. This uncertainty is reflected in the differences in the recommended threshold Hb for the initiation of treatment in the United States, and in Europe. In the United States, the threshold is reached when Hb levels decrease to < 109 Idl; in Europe, the threshold is reached when Hb levels drop to < 11g/dl [2]. The main goal of treatment is to reach the recommended target hemoglobin level of> 11/dl [European best practice guidelines (EBPG)] or target hemoglobin level of 11-12 g/dl [the national kidney foundation kidney disease outcomes quality initiative (NKF-K/DOQI)] while also increasing the effectiveness of therapy to optimize the cost :benefit ratio of anemia therapy [3]. To date, no study has found increased mortality with normalized Hb levels in patients with ESRD who do not have heart failure. On the other hand, several investigators have shown multiple benefits from Hb levels of 12 g/dl or greater[4]. In chronic Renal disease ,anemia appears earlier in men than in women, yet the recommended threshold Hb level for the initiation of EPO as well as the target to be attained (11-12 g/dl) remains equivalent for both genders[5] .The authors found that the early initiation of EPO in pre-dialysis patients with no severe anemia significantly slowed the progression of chronic Renal disease and delayed the initiation of renal replacement therapy[6].Hypo response to EPO is a problem in patients with ESRD. Iron therapy is vigorously advocated for renal anemia management. An analysis of data United States renal data system shows trends in the use of IV iron not explained by clinical indications. With the current pattern of IV iron use in patients with ESRD, the potential exists for excess accumulation of iron in the body [7]. Feldman et al found no statistically significant association between any level of iron administration and mortality, suggesting that confounding may have been responsible for their previous finding of an associated higher mortality [7]. Erythropoietin (EPO) deficiency is the main cause of anemia in uremic patients, but many other factors interfere with erythropoiesis and worsen anemia in hemodialysis (HD) patients. The main ones are GI bleeding, hyperparathyroidism, aluminum toxicity, toxic metabolites and deficiency of iron, foliates and vitamin B12. There is increasing evidence that oxidative stress plays a key role in the genesis and severity of dialysis anemia [8]. Oxidative stress corresponds to an imbalance between the production of reactive oxygen species (ROS), mainly the super oxide anion ,hydroxyl radical and protective mcchanisms. several enzymatic systems can detoxify ROS; Copper/Zink super oxide dismutase catalyses the conversion of super oxide anion to H202. In addition some micronutrients can prevent ROS harmful effects by nonenzymatic modes: reduced glutathione, a-Tocopherol or Vitamin E, which leads to formation of α-Tocopheroxyl radicals [8].Journal of Mashhad University of Medical Sciences No.90, Spring 2006 17 Oxidative stress reduces RBC survival, impairs the effect of EPO, and increases the susceptibility to hemolysis due to inflammatory, infectious and mechanical stimuli. The oxidative stress is enhanced in HD patients because Polymorphonuclear (PMN) leukocytes, activated by the contact with dialysis membranes, produce large amounts of oxygen free radicals [9].All these observations suggest that antioxidants could be useful as a collateral therapy for anemia in HD patients [10]. There is increasing evidence that EPO itself interferes with the oxidative event, but it is still not clear whether it enhances or has a protective effect against the oxidative stress). From these studies it appears that proper control of the oxidative status is essential to optimize treatment with EPO [11].Some encouraging results have been obtained with oral vitamin E, or a vitamin-E modified membrane, and reduce the oxidative stress in plasma and cells and the activation of leukocytes [12].One of the aims of this study is to evaluate the oxidative stress after treatment with oral vitamin E. Therefore, serum level of MDA, Alfa tocopheroxyl, glutathione and SOD in RBC has to be measured. As the level of α -Tocopheroxyl in RBC should be measured, it can not be concluded from this study that treatment with vitamin E significantly increase Hb level. Furthermore the study has not shown any benefit in responsiveness to EPO.It would have been better if some exclusion and inclusion criteria were added. Especially KT/V more than 1.2 is needed in inclusion criteria and hyperparathyroidism and hematologic disorder are needed in exclusion criteria.