Effect Of Intravenous Iron Supplement In Maintenance Hemodialysis Patients

Background: Iron deficiency is common in chronic kidney disease patients, especially in maintenance haemodialysis (MHD) patients. Lots of studies showed that the hemodialysis patients on EPO treatment could not maintain sufficient iron store through chalybeate orally alone. Intravenous iron supplementation has been widly used, and it surpasses oral iron in elevating the haematoglobin/haematocrit and decreaseing the dose of EPO. Recent studies indicated that intravenous irontherapy may intensify the fundament oxidative stress of endosomatic, then increase the hazard of angiosderosis and bacterial infection. However, most of the studies are centralized on the acute oxidative stress (only observed the change of oxidative stress during the dialysis 4 hours after intravenous irontherapy), few had paid attention on the long-term chronic damage with retain vein-reinfore ferri. Besides, the relation between vein-reinfore ferri and microinflam symptom of the MHD patients is unclear till now, and controversial existed on the use of anti-oxidant in the study of aggravated oxidative stress caused by long-term intravenous irontherapy. Therefore, this study first observed the impact of vein-ferri on the oxidative stress and inflammation condition in MHD patients, then we retrospectively analysised the vein-reinforce ferri and clinical date of 248 MHD patients in the past 3 years, including the dose of vein-reinfore chalybeate and the impact of intravenous irontherapy on cardiovascular complication, infection and patient prognosis. At last, we investigated the protective role of Vit E to the oxidative damage caused by the long-term use of intravenous irontherapy.Methods: (1) 90 MHD patients were included and divided randomly into three groups: intravenous irontherapy group (n=35), chalybeate orally group (n=35) and control group (n=20). We observed the hematology, ferri correlatedindex, and inflammation indexes such as serum C reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), and oxidative stress markers such as peroxide dismutase (SOD), hematoplasma malonaldehyde (MDA) and AOPP, monitoring their adverse reactions. (2) 248 patients were enrolled who started MHD treatment from December 2003, to December 2006. These patients were divided into three groups: group A, nonvein-ferri group (0mg/year, n=67), group B, routine dose vein-ferri group (0-5000mg/year, n=119), and group C, large dose vein-ferri group (≥5000/year, n=62). All patients were followed up until December 2006. Indexes, including CRP, haemoglobin (Hb), biochemical marker, serum ferritin (SF) and TSAT, were recorded pre-dialysis per quarter. Angiosclerosis of arteria carotis, cardiovascular event, hospitalization, and death were analyzed to investigate the correlations between intravenous irontherapy dose and cardiovascular event, hospitalization rate, and mortality. (3) 65 patients who were on intravenous irontherapy sustained dose were randomly divided into two groups: oral vitamin E group (400mg/d for 3 months) and control group. Vit E, CRP, IL-6, IL-10, TNF-α, MDA, SOD and AOPP before and after offered medical intervene were observed. Results: (1) After 8 weeks, the levels of plasma MDA and AOPP in the group of intravenous iron supplement were significantly higher than pretherapy(P<0.05), the level of SOD was significantly lower than pretherapy (P<0.05); the levels of CRP, IL-6, IL-18, TNF-α in the group of intravenous iron supplement were significantly higher than pretherapy (P<0.05 ) , while the oxidative stress, inflammation indexes in oral group and iron non-taken groups did not show any difference. After 8 weeks, both the levels of MDA were positively relevant to SF (r=0.78, P<0.05); (2) 248 MHD patients were divided into three groups, 67 patients in group A (0mg/y) ,119 patients in group B(0-5000mg/ y) , and 62 patients in group C (≥5000mg/ y) . Cardiovasculars events, carotid angiosclerosis, incidence of bacterial infection, hospitalizationa and mortality in the high dosage of intravenous iron supplement group werehigher than other groups. Age and the level of CRP in high dosage group were significantly higher than the other groups, but the level of Hb and Alb in this group were lower than the other groups. Multiple regression analysis indicated that age, diabetes, haemoglobin, albumin and central venous catheters were related to the dosage of intravenous iron supplement of the patients in the group whose dosage were ≥5000mg/y. Mutiple regression analysis indicated that the dosage of intravenous iron supplement wasn't the independent risk factor of the above complications. (3) We distributed 65 patients into experimental group (n=34 oral administration vitamin E 400mg/d) and control group (n=31 vitmin E non-taken). Isodose intravenous iron supplement were given to the two groups for therapy. There were no significantly deviations about the level of vitamin E, AOPP, MDA and SOD of the patients of the two groups in the beginning of the observation. After given 400mg/d vitamin E for 3 months,the level of vitamin E and the activity of SOD in experimental group were significantly higher than that of control group (P < 0.05, P < 0.05); the levels of AOPP and MDA were significantly lower than that of control group ( P < 0.05); there were no significantly deviation about the inflammation indexes of CRP, IL-6, IL-10,IL-18 and TNF-α in the beginning of the observation between the two groups; the levels of CRP, TNF-α in the experimental group were significantly lower than that of control group at the end of the observation( P < 0.05), the levels of IL-6. IL-10and IL-18 were lower than the beginning of the observation, but there was no significantly deviation, while the above indexes hadn't significantly deviation in the control group. The levels of CRP. TNF-α in experimental group were significantly lower than that of control group (P < 0.05).Conclusion: (1) After the therapy of intravenous iron supplement for the MHD patients, though the anemia and asiderosis had obvious improvement, it may initiate the oxditive stress and inflammation at the same time. (2) Age, inflammation, diabetes, deep vein and sera albumin of the MHD patients contribute the dosage of the intravenous iron supplement, and these factors areclosely related to the development of the complications and prognosis, which indicate intravenous iron supplement is not the major factor that cause MHD patients angiosclerosis, the incidence of bacterial infection and high mortality. Demixing analysis of the intravenous iron supplement indicated that when the dosage of the intravenous iron supplement is lower than 5000mg/y, the incidence of the complications above would significantly increase. (3) Vitamin E could improve the oxidative stress and inflammation of hemodialysis patients who use the iron supplement, and increase the availability of the intravenous iron supplement.