***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Anemia , a common complication of chronic kidney disease , usually develops as a consequence of erythropoietin deficiency . Recombinant human erythropoietin ( epoetin alfa ) is indicated for the correction of anemia associated with this condition . However , the optimal level of hemoglobin correction is not defined . METHODS In this open-label trial , we studied 1432 patients with chronic kidney disease , 715 of whom were r and omly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter . The median study duration was 16 months . The primary end point was a composite of death , myocardial infa rct ion , hospitalization for congestive heart failure ( without renal replacement therapy ) , and stroke . RESULTS A total of 222 composite events occurred : 125 events in the high-hemoglobin group , as compared with 97 events in the low-hemoglobin group ( hazard ratio , 1.34 ; 95 % confidence interval , 1.03 to 1.74 ; P=0.03 ) . There were 65 deaths ( 29.3 % ) , 101 hospitalizations for congestive heart failure ( 45.5 % ) , 25 myocardial infa rct ions ( 11.3 % ) , and 23 strokes ( 10.4 % ) . Seven patients ( 3.2 % ) were hospitalized for congestive heart failure and myocardial infa rct ion combined , and one patient ( 0.5 % ) died after having a stroke . Improvements in the quality of life were similar in the two groups . More patients in the high-hemoglobin group had at least one serious adverse event . CONCLUSIONS The use of a target hemoglobin level of 13.5 g per deciliter ( as compared with 11.3 g per deciliter ) was associated with increased risk and no incremental improvement in the quality of life . ( Clinical Trials.gov number , NCT00211120 [ Clinical Trials.gov ] . ) BACKGROUND Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests . Reticulocyte hemoglobin content ( CHr ) is a test that has shown promise for improved diagnosis in preliminary studies . The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr . METHODS A total of 157 hemodialysis patients from three centers were r and omized to iron management  based on ( group 1 ) serum ferritin and transferrin saturation , or ( group 2 ) CHr . Patients were followed for six months . Treatment with intravenous iron dextran , 100 mg for 10 consecutive treatments was initiated if ( group 1 ) serum ferritin < 100 ng/mL or transferrin saturation < 20 % , or ( group 2 ) CHr < 29 pg . RESULTS There was no significant difference between groups in the final mean hematocrit or epoetin dose . The mean weekly dose of iron dextran was 47.7 + /- 35.5 mg in group 1 compared to 22.9 + /- 20.5 mg in group 2 ( P = 0.02 ) . The final mean serum ferritin was 399.5 + /- 247.6 ng/mL in group 1 compared to 304.7 + /- 290.6 ng/mL in group 2 ( P < 0.05 ) . There was no significant difference in final TSAT or CHr . Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation ( 3.4 % vs. 43.6 % and 39.5 % , respectively ) . CONCLUSIONS CHr is a markedly more stable analyte than serum ferritin or transferrin saturation , and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure BACKGROUND Iron deficiency is a frequent cause of recombinant human erythropoietin (rhEPO)-resistant anemia in hemodialysis patients . Both reticulocyte hemoglobin content ( CHr ) and transferrin saturation ( TSAT ) have been proposed as markers of iron deficiency , but it is unclear which parameter is superior . METHODS To compare the efficacy of CHr and TSAT as an indicator for treatment of iron deficiency , we conducted a single-center , open-label , prospect i ve , r and omized , controlled trial at the Kidney Center in Shinraku-en Hospital of 197 Japanese patients on chronic hemodialysis . After 4 weeks of run-in period during which iron supplementation was suspended , 100 patients who were r and omized to the CHr group received 240 mg iron colloid intravenously over 2 weeks when CHr less than 32.5 pg , and 97 patients who were r and omized to the TSAT group received the same doses of iron colloid when TSAT less than 20 % . We measured the  rhEPO dose needed to maintain pre study hematocrit levels , hematocrit , CHr , TSAT , serum ferritin , percentage of hypochromic red blood cells , and total iron administered . RESULTS Sixteen weeks later , 94 patients in the CHr group and 89 patients in the TSAT group finished the study . The doses of rhEPO required decreased by 35.8 % ( 4081 to 2629 U/week , P < 0.005 ) in the TSAT group , but not significantly in the CHr group ( 4121 to 3606 U/week ) . Although CHr increased promptly after the iron administration in both groups , TSAT increased only in the TSAT group . CONCLUSIONS Although CHr reflects the iron status more sensitively , TSAT is a better clinical marker for iron supplementation therapy Background / Aims : Renal anemia is one of the commonest complications of chronic renal failure . Iron deficiency is the most common factor which affects the efficacy of recombinant human erythropoietin ( EPO ) therapy . Intravenous ( i.v . ) iron preparations are commonly used in Western countries , but iron sucrose is seldom used in Chinese patients on maintenance hemodialysis . The aim of the present study was to explore the safety and efficacy of i.v . iron sucrose in Chinese patients on maintenance hemodialysis and to explore the optimal administration frequency . Methods : One hundred and thirty-six patients on maintenance hemodialysis were involved in this r and omized , controlled , parallel-group , single-center trial . Seventy patients received i.v . iron sucrose ( Venofer ® , delivering 100 mg iron ) twice a week for 8 weeks , then once a week for another 4 weeks . The other 66 patients received oral ( p.o . ) ferrous succinate 200 mg t.i.d . for 12 weeks . Levels of serum ferritin ( SF ) , transferrin saturation ( TSAT ) , hemoglobin ( Hb ) and hematocrit ( Hct ) were assessed at baseline and then again after 4 , 8 and 12 weeks of treatment . Results : There were no differences between i.v . and p.o . groups in terms of sex , age , duration of hemodialysis , dialysis frequency per week , EPO dosage per week , the level of intact parathyroid hormone , serum creatinine , blood urea nitrogen , or hematological parameters at baseline . After 8 and 12 weeks of treatment , mean Hb concentration and Hct were significantly increased in the i.v . group , and were also significantly higher than those in the p.o . group . Levels of SF and TSAT were also significantly increased in the i.v . group , and significantly higher than in the p.o . group . After 8 weeks , the response rate in the i.v . group was 88.6 % , which was significantly higher than that in the p.o . group . The mean EPO dose was significantly lower in the i.v . group than the p.o . group . Hb , Hct , SF and TSAT levels were maintained between 8 and 12 weeks in the i.v . group despite the decrease in dose frequency . There were no adverse events related to i.v . iron administration . Twenty-two patients in the p.o . group had adverse gastrointestinal effects . After 12 weeks , the cost of EPO + i.v . iron was significantly higher than the cost of EPO + p.o . iron . Conclusion : Intravenous iron sucrose can effectively increase serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and is well tolerated . Infusion of i.v . iron sucrose 100 mg per week can maintain serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and can permit reductions in the required dose of EPO . However , the total cost of i.v . iron is relatively high BACKGROUND AND OBJECTIVES Hepcidin is a key regulator of iron homeostasis , but its study in the setting of chronic kidney disease ( CKD ) has been hampered by the lack of vali date d serum assays . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This study reports the first measurements of bioactive serum hepcidin  using a novel competitive ELISA in 48 pediatric ( PCKD2 - 4 ) and 32 adult ( ACKD2 - 4 ) patients with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD ( PCKD5D ) on peritoneal dialysis . RESULTS When compared with their respective controls ( pediatric median = 25.3 ng/ml , adult = 72.9 ng/ml ) , hepcidin was significantly increased in PCKD2 - 4 ( 127.3 ng/ml ) , ACKD2 - 4 ( 269.9 ng/ml ) , and PCKD5D ( 652.4 ng/ml ) . Multivariate regression analysis was used to assess the relationship between hepcidin and indicators of anemia , iron status , inflammation , and renal function . In PCKD2 - 4 ( R(2 ) = 0.57 ) , only ferritin correlated with hepcidin . In ACKD2 - 4 ( R(2 ) = 0.78 ) , ferritin and soluble transferrin receptor were associated with hepcidin , whereas GFR was inversely correlated . In PCKD5D ( R(2 ) = 0.52 ) , percent iron saturation and ferritin were predictors of hepcidin . In a multivariate analysis that incorporated all three groups ( R(2 ) = 0.6 ) , hepcidin was predicted by ferritin , C-reactive protein , and whether the patient had stage 5D versus stages 2 to 4 CKD . CONCLUSIONS These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance INTRODUCTION Although clinical use of recombinant human erythropoietin ( rHuEPO ) since 1989 has improved anemia in most end-stage renal disease patients , there are still many hemodialysis patients unable to maintain an adequate hematocrit ( HCT ) without large doses of rHuEPO . This suggests that anemia is not solely a consequence of rHuEPO deficiency , but may be due to other factors including functional iron deficiency . Since the optimal prescription for iron replacement is not yet known , we evaluated the effect of intravenous iron dextran ( IVFe ) infusion on serum ferritin ( SFer ) concentration and rHuEPO dose . Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative st and ard of 100 ng/ml to determine whether , and by what degree rHuEPO dose could be lowered . METHODS HD patients on i.v . rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33 % were enrolled . Subjects were divided as follows : Group 1 : target SFer of 200 ng/ml , Group 2 : target SFer of 400 ng/ml . Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target . HCT was maintained between 32.5 % and 36 % by adjusting rHuEPO dosage . RESULTS Mean SFer concentration at the study conclusion in Group 1 : 261 ng/ml ; Group 2 : 387 ng/ml . The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week ( 250 - 219 U/kg bw/wk ) while in Group 2 it was 154 U/kg body weight/week ( 312 - 158 U/kg bw/wk ) ( p < 0.001 ) . There was no difference in HCT between groups . Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin ( EPO )  , a prospect i ve r and omized controlled study was design ed to investigate this issue . All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were r 
    Output:
    
Significant reductions in ESA dosing may be achieved with optimal intravenous iron usage in the haemodialysis population , and suboptimal iron use may require higher ESA dosing to manage anaemia