Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Comparative study of intravenous ascorbic acid versus low-dose desferroxamine in patients on hemodialysis with hyperferritinemia. Clinical update: intravenous iron for anaemia Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants. Effect of iron-supplemented total parenteral nutrition in patients with iron deficiency anemia. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Efficacy of IV iron compared to oral iron for increment of haemoglobin level in anemic chronic kidney disease patients on erythropoietin therapy. Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness. Effect of intravenous iron sucrose in peritoneal dialysis patients who receive erythropoiesis-stimulating agents for anemia: a randomized, controlled trial. Correction of Uremic Iron Deficiency Anemia in Hemodialyzed Patients: A Prospective Study A Randomized, Controlled Trial of the Effects of Adding Vitamin B12 and Folate to Erythropoietin for the Treatment of Anemia of Prematurity Iron-containing micronutrient powder provided to children with moderate-to-severe malnutrition increases hemoglobin concentrations but not the risk of infectious morbidity: a randomized, double-blind, placebo-controlled, noninferiority safety trial. Intravenous versus oral iron supplementation for preoperative stimulation of hemoglobin synthesis using recombinant human erythropoietin. [Effectiveness of oral versus parenteral iron substitution in autologous blood donors]. Changes in hepcidin and reticulocyte hemoglobin equivalent levels in response to continuous erythropoietin receptor activator administration in hemodialysis patients: a randomized study. Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients Characterization and Differentiation of Iron Status in Anemic Very Low Birth Weight Infants Using a Diagnostic Nomogram Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C Ferumoxytol for treating iron deficiency anemia in CKD. Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy-associated anemia. Intermittent versus maintenance iron therapy in children on hemodialysis: a randomized study Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients.
In recent times , therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents ( ESAs ) have decreased . Here we used a prospect i ve , observational , multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy . The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables . The risks of cerebrovascular and cardiovascular disease ( CCVD ) , infection , and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level . Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease . Moreover , the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level . The risks of CCVD , infection , and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron . Thus , there is a high risk of death and /or adverse events in patients with hemoglobin levels outside the target range , in those with high-amplitude hemoglobin fluctuations , in those with consistently high serum ferritin levels , and in those with high-amplitude ferritin fluctuations BACKGROUND In patients on hemodialysis ( HD ) , parenteral iron improves the response to recombinant human erythropoietin ( rhuEPO ) therapy , but in some subjects it produces an iron overload , increasing their morbidity and mortality rates . In these cases , iron administration must be discontinued . This study aim ed to investigate the efficiency of treatment with ascorbic acid ( AA ) or desferroxamine ( DFO ) to mobilize and reduce iron stores , and to determine the effect of these compounds on erythropoiesis . METHODS We performed a prospect i ve and r and omized trial over 6 months , which included 27 patients with serum ferritin levels > 800 ng/mL , TSAT > 30 % and stabilized hemoglobin ( Hb ) and rhuEPO doses . All patients had previously received parenteral iron ( Ferlecit ) . Nine patients received 200 mg of intravenous ( i.v . ) AA 3 times/week and nine patients received 1 mg/Kg/week of DFO ; the remaining nine patients were the control group . RESULTS There were no significant differences in iron loss or mobilization due to dialysis . When Ferlecit was discontinued , functional iron did not vary and the epoetin resistance index ( rhuEPO dose/Hb ) was reduced by 21 % in the i.v . AA group . In the DFO and control groups , functional iron levels fell . In the DFO group the epoetin resistance index increased by 20 % , with no modifications in the control group . There was a positive correlation between transaminases and serum ferritin . CONCLUSIONS In HD patients with an iron overload , neither i.v . AA administration or low-dose DFO increased iron mobilization or iron loss due to dialysis . I.v . AA administration allows elimination of iron from stores without any drop in the functional iron produced by discontinuing parenteral maintenance iron ; it also improves the response to rhuEPO . DFO did not elicit any positive effects on erythropoiesis For nearly half a century , parenteral iron has been considered dangerous and for use only in extreme situations and when oral iron was not tolerated . This proscription was based largely on poorly characterised and infrequent anaphylactoid reactions to the high-molecular-weight dextran preparation ( Imferon ) that for most of this time was the only product available . Moreover , when parenteral iron was necessary , the recommended approach was small intramuscular doses ( ≤100 mg ) , even after intravenous administration of the total iron defi cit as a single dose or as repetitive boluses was shown to be as safe and eff ective as the intramuscular route . This mindset persists despite the subsequent introduction of low-molecular-weight iron dextran and two iron salt preparations , ferric gluconate and iron saccharate ( the latter is also known as iron sucrose ) , all of which are associated with fewer serious adverse events than the high-molecular-weight dextran . The introduction of recombinant erythropoietin for dialysis patients was associated with the development , in some individuals , of functional iron defi ciency that limited effi cacy . Intravenous iron , unlike oral iron , improves erythropoietic response in dialysis patients , and is now routinely used . The discovery of the iron regulatory peptide , hepcidin , has improved our underst and ing of the anaemia of chronic infl ammatory states , including cancer . Hepcidin is upregulated in these conditions , result ing in increased synthesis by the liver . Hepcidin inhibits iron transport across cell membranes , which decreases the accessibility of storage iron and gastrointestinal absorption of dietary iron , leading to an increased frequency of iron-restricted erythropoiesis , especially during therapy with recombinant erythropoietin . The most frequent laboratory fi ndings during the anaemia of chronic infl ammation are hypoferraemia and a low percent transferrin saturation , although these fi ndings are not always present . The increasing use of recombinant erythropoietin to treat anaemia in patients with chronic diseases has exp and ed the population of patients with functional iron defi ciency and increased interest in safe rational approaches to parenteral iron therapy . There is mounting evidence that anaemic patients with cancer undergoing chemotherapy and receiving  recombinant erythropoietin respond better when parenteral iron is administered . This benefi t is independent of baseline iron variables , such as ferritin , low percentage transferrin saturation , and stainable marrow haemosiderin , leaving the clinician in need of laboratory variables to reliably detect iron-restricted erythropoiesis in patients with infl ammatory illnesses and to predict improvement of erythropoietic response to parenteral iron in the setting of infl ammatory illness . Two new laboratory measures look promising : percent hypochromic red blood cells and reticulocyte haemoglobin content . These tests are reliable and accurate correlates of functional iron defi ciency . Although these investigations are not yet widely available , their use will probably exp and and guide identifi cation of functional iron defi ciency and rational intervention with parenteral iron . Currently , four parenteral iron preparations are available ( table ) . No r and omised trials have compared the safety and effi cacy of any of these agents . The largest retrospective review of dialysis experience suggests that most serious adverse events have been associated with the high-molecular-weight iron dextrans ( Imferon , which is no longer available and the current preparation , Dexferrum ) and are rare ( < 1:200 000 ) with the low-molecular-weight iron dextran or the two iron salts ( fi gure ) . Adverse event rates might be somewhat higher in patients with infl ammatory diseases in which immune-mediated drug reactions  may be observed more commonly than in dialysis patients . Some of the adverse clinical experience with parenteral iron is due to inappropriate supportive care . Myalgias , when they include chest and back discomfort , are mistakenly described as anaphylaxis , prompting Low – molecular – weight iron dextran Iron saccharate Ferric gluconate High – molecular – weight iron OBJECTIVE To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin ( EPO ) in very low birth weight ( VLBW ) infants . METHODS A prospect i ve , controlled , r and omized , unmasked trial lasting 21 days was performed in 29 clinical ly stable VLBW infants < 31 weeks ' gestation and < 1300 g birth weight not treated with red blood cell transfusions during the study period . Mean ( + /- st and ard error of the mean ) age at study entry was 23 + /- 2.9 days . After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex ( IPC ) , participants were r and omized to receive 18 days of treatment with : 1 ) oral IPC alone ( oral iron group ) ; 2 ) 300 U of recombinant human EPO ( r-HuEPO ) kg/day and daily oral IPC ( EPO + oral iron group ) ; 3 ) 2 mg/kg/day of intravenous iron sucrose , r-HuEPO , and oral iron ( intravenous iron + EPO group ) . To assess efficacy of the 3 treatments , serial blood sample s were analyzed for hemoglobin ( Hb ) , hematocrit ( Hct ) , reticulocyte count , red blood cell indices and plasma levels of transferrin , transferrin receptor ( TfR ) , ferritin , and iron . Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde ( MDA ) and o-tyrosine . RESULTS At the end of treatment , Hb , Hct , reticulocyte count , and plasma TfR were markedly higher in both of the EPO-treated groups , compared with the oral iron group . At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group , compared with the EPO + oral iron group . During treatment , plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups . By the end of treatment , ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups . Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups , plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sample d at the end of the 2-hour parenteral iron infusion , compared with values observed immediately before and after parenteral iron-dosing . CONCLUSIONS In stable VLBW infants receiving EPO treatment , parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small , but significant , augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone . However , to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury , we suggest that the parenteral iron dose used should be reduced and /or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity Iron deficiency anemia is common among hospitalized patients , and blood losses from diagnostic phlebotomy increase the likelihood of a negative iron balance . The role for iron supplementation of total parenteral nutrition ( TPN ) in these patients is unclear . Twenty-three patients with iron deficiency anemia were identified . Twelve patients were r and omized to receive TPN without iron ( group 1 ) and 11 received TPN supplemented with 10 mg of iron as iron dextran daily ( group 2 ) . Both groups were matched for age , serum iron studies , red cell indices , and hemogram . After a 7-d period , the mean serum iron in group 2 increased from 10 to 26 micrograms/dL , with an increased transferrin saturation from 7.3 to 15.3 % ( each , p < 0.05 ) . No changes in total iron binding capacity , ferritin , reticulocyte count , hemoglobin , hematocrit , or mean corpuscular volume were observed in the two groups . The incidence of infectious complications was not different between both groups . We conclude that iron supplementation of TPN appears safe and is effective in increasing serum iron levels . The use of iron-supplemented short-term TPN needs to be further studied given no change in red cell indices , hemoglobin , hematocrit , or transfusion requirement BACKGROUND Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease ( NDD-CKD ) frequently requires parenteral iron replacement , but existing therapies often require multiple administrations . We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose ( FCM ) , a non-dextran parenteral iron permitting large single-dose infusions , versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD . METHODS A total of 2584 participants were r and omized to two doses of FCM 750 mg in one week , or iron sucrose 200 mg administered in up to five infusions in 14 days . The primary efficacy endpoint was the mean change to highest hemoglobin from baseline to Day 56 . The primary composite safety endpoint included all-cause mortality , nonfatal myocardial infa rct ion , nonfatal stroke , unstable angina , congestive heart failure , arrhythmias and hyper- and hypotensive events . RESULTS The mean hemoglobin increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group ( 95 % CI , 0.13 - 0.28 ) . Similar results were observed across all subgroups , except Stage 2 CKD . More subjects in the FCM group achieved a hemoglobin increase of ≥ 1.0 g/dL between baseline and Day 56 ( 48.6 versus 41.0 % ; 95 % CI , 3.6 - 11.6 % ) . There was no significant difference between FCM and iron sucrose recipients with respect to the primary composite safety endpoint , including the major adverse cardiac events of death , myocardial infa rct ion , or stroke . A significant difference in the number of protocol -defined , predominantly transient hypertensive episodes was observed in the FCM group . CONCLUSIONS Two 750-mg infusions of FCM are a safe and effective alternative to multiple lower dose iron sucrose infusions in NDD-CKD patients with iron-deficiency anemia INTRODUCTION Anemia is the most common finding in chronic kidney disease patients .  Iron supplements are commonly prescribed for these patients with or without erythropoietin therapy by means of oral and intravenous iron . Both oral and intravenous irons have their own advantage and disadvantage , and the efficacy is also different . The objective of the study is to analyze the efficacy of oral and intravenous iron in chronic kidney disease patients on erythropoietin therapy , an erythropoiesis stimulating agents for increment of haemoglobin . METHODS This is a prospect i ve study comparing intravenous iron to oral iron in chronic kidney disease patients who underwent maintenance hemodialysis at different centers and visited Kathm and u Medical College Teaching Hospital from April 2010 to April 2011 . Patients having a haemoglobin level of < 11 g/dl , transferrin saturation ( TSAT ) < 25 % , ferritin < 300ng/ml and who were on erythropoietin therapy were allocated alternately into two groups to receive oral iron ( iron fumarate ) or IV iron ( iv sucrose ) .  Haemoglobin was measured after 30 days of therapy . RESULTS A significant increase in haemoglobin levels was observed in both groups . But the mean haemoglobin increment was more in the IV iron group than in the oral iron group . Sixty percent 60 % of patients in the IV iron group had an increase in the haemoglobin level of more than 1gm/dl while only 20 % of the oral iron group had this increase . CONCLUSIONS Intravenous iron therapy is more effective in raising the hemoglobin level in hemodialysis dependent chronic kidney disease patients BACKGROUND Critical illness is characterized by hypoferremia , iron-deficient erythropoiesis ( IDE ) , and anemia . The relative risks and benefits of iron supplementation in this setting are unknown . METHODS Anemic , critically ill surgical patients with an expected intensive care unit length of stay ( ULOS ) > or= 5 days were r and omized to either enteral iron supplementation ( ferrous sulfate 325 mg three times daily ) or placebo  until hospital discharge . Outcomes included hematocrit , iron markers ( i.e. , serum concentrations of iron , ferritin , and erythrocyte zinc protoporphyrin [ eZPP ] ) , red blood cell ( RBC ) transfusion , transfusion rate ( mL RBC/ study day ) , nosocomial infection , antibiotic days , study length of stay ( LOS ) , ULOS , and death . Iron-deficient erythropoiesis was defined as an elevated eZPP concentration . RESULTS Two hundred patients were r and omized ; 97 received iron , and 103 received placebo .  Socio-demographics , baseline acuity , hematocrit , and iron markers were similar in the two groups . No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days . However , patients treated with iron were significantly less likely to receive an RBC transfusion ( 29.9 % vs. 44.7 % , respectively ; p = 0.03 ) and had a significantly lower transfusion rate ( 22.0 mL/day vs. 29.9 mL/day ; p = 0.03 ) . Subgroup analysis revealed that these differences were observed in patients with baseline IDE only . Iron and placebo groups did not differ with respect to incidence of infection ( 46.8 % vs. 48.9 % ; p = 0.98 ) , antibiotic days ( 14 vs. 16 ; p = 0.45 ) , LOS ( 14 vs. 16 days ; p = 0.24 ) , ULOS ( 12 vs. 14 days ; p = 0.69 ) , or mortality rate ( 9.4 % vs. 9.9 % ; p = 0.62 ) . CONCLUSIONS Enteral iron supplementation of anemic , critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion . A trial comparing enteral and parenteral iron supplementation in this setting is warranted ( Clinical Trials.gov number , NCT00450177 ) Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents ( ESA ) , r and omized , controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis ( PD ) patients . In a multicenter trial , patients who had anemia , PD-dependent chronic kidney disease , stable ESA therapy , and a broad range of iron status ( ferritin < or = 500 ng/ml , transferrin saturation < or = 25 % ) were r and omly assigned to receive either 1 g of iron sucrose intravenously in three divided doses ( 300 mg over 1.5 h on days 1 and 15 , 400 mg over 2.5 h on day 29 ) or no supplemental iron . No serious adverse drug events occurred after intravenous iron administration . The primary end point , peak hemoglobin increase , was higher ( 1.3 + /- 1.1 versus 0.7 + /- 1.1 , mean + /- SD ; P = 0.0028 ) , and anemia intervention ( transfusion , increase in ESA dose , or intravenous iron therapy not called for in protocol ) occurred later ( P = 0.0137 ) and less often in intravenous iron-treated patients compared with untreated control subjects ( one of 66 [ 1.3 % ] versus five of 30 [ 16.7 % ] ) . Among patients who did not require intervention , iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects . Baseline iron status did not predict responsiveness to intravenous iron therapy . Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy This prospect i ve study was design ed to evaluate the eventual correction of anemia and iron status in 39 iron-deficient uremics starting hemodialysis . Nine patients ( control group ) had no iron supplementation  , 10 had oral ferrous iron , and 20 were treated with intravenous iron gluconate . Follow-up periods were 12 months for the control group and 26 months for patients treated with oral or intravenous iron . No patient was treated with erythropoietin . At zero time , all patients were anemic ( Hb < 78 g/l ) and showed signs of severe iron deficiency , diagnosed on the basis of depleted bone marrow iron stores , reduced hemoglobin iron , and transferrin saturation < 21 % . The hemoglobin levels , observed in patients of the control and the oral iron groups at the end of the follow-up periods , were not significantly different from those detected at zero time . In contradistinction , patients treated with intravenous iron showed after 26 months of follow-up a significant increase of blood hemoglobin values , reaching a mean value of 126 g/l . So far , this evidence supports both the concept that iron absorption is compromised in chronic uremics and that the parenteral way is the more effective route for iron replacement in this specific group of patients BACKGROUND . Premature infants , especially those with birth weights of < 1500 g , often suffer from anemia of prematurity and associated problems . Erythropoietin therapy is a safe effective way to prevent and to treat anemia of prematurity . We hypothesized that combined administration of vitamin B12 and folate with erythropoietin and iron would enhance erythropoietin-induced erythropoiesis . METHODS . In a r and omized , controlled trial , 64 premature infants ( birth weight : 801–1300 g ) receiving erythropoietin and iron supplementation  were assigned r and omly to receive either vitamin B12 ( 3 μg/kg per day ) and folate ( 100 μg/kg per day ) ( treatment group ) or a lower dose of folate ( 60 μg/kg per day ) ( control group ) . RESULTS . During the 4-week observation period , vitamin B12 and folate  enhanced erythropoietin-induced erythropoiesis significantly , as indicated by a 10 % increase in red blood cell counts , compared with folate alone . Hemoglobin and hematocrit levels remained stable in the treatment group , whereas they decreased in the control group  . Vitamin B12 levels in the treatment group increased over baseline and control values , whereas red blood cell folate levels were comparable between the groups . Subsequent analysis showed slight nonsignificant differences in baseline red blood cell count , hemoglobin level , hematocrit level , and mean corpuscular volume values , which must be addressed as a limitation . CONCLUSIONS . With the limitation of a slight imbalance in baseline data between the study groups , combined therapy with vitamin B12 , folate , erythropoietin , and orally and intravenously administered iron seemed more effective in stimulating erythropoiesis among premature infants , compared with erythropoietin , iron , and low-dose folate alone . Additional trials are necessary to confirm these data BACKGROUND A link between the provision of iron and infectious morbidity has been suggested , particularly in children with malnutrition . Two meta-analyses concluded that iron is not harmful , but malnourished children were underrepresented in most available studies . OBJECTIVE This study evaluated the effect of iron-containing micronutrient powder ( iron MNP ) on infectious morbidities when provided to children with moderate-to-severe malnutrition and anemia . DESIGN A r and omized , double-blind , placebo-controlled , noninferiority safety trial using a 2-mo course of daily iron MNP or placebo powder ( PP ) was conducted in 268 Bangladeshi children aged 12 - 24 mo with moderate-to-severe malnutrition ( weight-for-age z score ≤ -2 ) and a hemoglobin concentration between 70 and 110 g/L. The primary endpoint was a composite of diarrhea , dysentery , and lower respiratory tract infection episodes ( DDL ) recorded through home visits every 2 d during the intervention and then weekly for 4 mo . The noninferiority margin was 1.2 . Secondary endpoints included hemoglobin and anthropometric changes at 2 and 6 mo . All deaths and hospitalizations were documented . To capture seasonal variation , the study was repeated in the winter and summer with 2 distinct groups . An intention-to-treat analysis of recurrent events was performed by using the univariate And erson-Gill model . RESULTS The baseline characteristics of the subjects were similar . Analysis of phase-aggregated DDL data showed that iron MNP was not inferior to PP ( relative risk : 0.81 ; 95 % CI : 0.62 , 1.04 ) and improved hemoglobin concentrations ( P < 0.0001 ) . We recorded no deaths , and hospitalizations were rare . CONCLUSION Iron MNP is safe and efficacious when provided to children aged 12 - 24 mo with moderate-to-severe malnutrition and anemia . This trial is registered at clinical trials.gov as NCT00530374 To compare two modalities of iron supplementation for the preoperative stimulation of erythropoiesis using recombinant human erythropoietin ( rhEPO ) , 12 adults in normal hemoglobin and iron status due for elective surgery were r and omized to rhEPO 200 U/kg body weight subcutaneously twice weekly combined with either iron sucrose 200 mg intravenously twice weekly or iron sulfate 160 mg/day orally , for 3 weeks preoperatively . Efficacy was measured by the increases over baseline in hemoglobin , reticulocyte count , and ferritin determined 3 days before surgery ; preoperative reticulocyte count and ferritin were significantly higher with intravenous iron , whereas the only significant intragroup increases in hemoglobin between time points also occurred in this group . Intravenous iron significantly boosts the hematopoietic response to rhEPO and prevents iatrogenic iron depletion in otherwise healthy c and i date s for elective surgery OBJECTIVE Is intravenous iron therapy as efficient as oral iron supplementation in patients undergoing autologous blood donation ? DESIGN Prospect i ve , r and omized study . PATIENTS AND SETTING 30 male and 30 female patients , separated into two groups were examined prior to total hip replacement . INTERVENTIONS Patients of group O were given 6 x 50 mg Fe2 + aspartate/day orally , and patients of group P were given 0.75 mg/kg BW complex-bound Fe3 + once a week by infusion . In both groups therapy was started two weeks prior to the first donation . The substitution was continued the following six weeks until surgery . Hemoglobin , ferritin plasma concentrations and reticulocytes were monitored . The appearance of unwanted side effects was studied by question naire . RESULTS Hb decreased significantly in both groups . A difference was seen in the reticulocyte count and in the ferritin levels . Here we found a significant increase in group P compared with group O. 40 % of the patients who took the iron orally complained about unwanted side effects such as obstipation and diarrhoea , whereas none of the patients of the parenteral group had any complaints . CONCLUSIONS Stimulation of the erythropoiesis appeared to be more efficient with intravenous iron therapy than with oral iron supplementation . The oral dose has in about 40 % unwanted side effects . For this reason a parenteral iron therapy can be considered , but one must be aware that in some cases dangerous anaphylactic reactions could appear Inadequate iron availability limits the response to erythropoiesis-stimulating agents ( ESA ) and hepcidin is a key regulator of iron metabolism . However , there is little information concerning time-dependent changes in hepcidin in response to the change of accelerated iron dem and due to ESA-induced erythropoiesis . In this study , iron-related parameters , including hepcidin levels , were explored in comparison to patients receiving  continuous erythropoietin receptor activator ( CERA ) and epoetin beta ( EPO )  treatment . Ninety-four patients were r and omized to receive monthly CERA  ( N = 47 ) or EPO  three times/week ( N = 47 ) . After the titration period , hemoglobin levels and iron-related parameters were examined . Data for 71 patients were evaluated  ( CERA , N = 34 ; EPO , N = 37 ) . Compared with EPO treatment , CERA treatment caused significant decreases within 1 week in hepcidin ( -93.5 ± 46.9 vs. -1.3 ± 38.3 ng/mL , P < 0.01 ) , reticulocyte hemoglobin equivalent ( Ret-He ) ( -4.03 ± 2.64 vs. -1.13 ± 1.41 pg , P < 0.01 ) , ferritin ( -58.9 ± 30.5 vs. -12.2 ± 23.8 ng/mL , P < 0.01 ) and transferrin saturation ( -13.2 ± 9.1 vs. 1.0 ± 11.9 % , P < 0.01 ) and significant increases within 2 weeks in the levels of hemoglobin ( 0.42 ± 0.38 vs. -0.02 ± 0.48 g/dL , P < 0.01 ) . In conclusion , hepcidin , Ret-He , ferritin and transferrin saturation levels decreased within 1 week and hemoglobin increased within 2 weeks after CERA administration . Time course of iron-related parameters including hepcidin demonstrated accelerated iron utilization appropriately according to ESA-induced erythropoiesis Ferric pyrophosphate citrate ( FPC ) is a water-soluble iron salt administered via dialysate to supply iron directly to transferrin . The PRIME study tested whether treatment with FPC could reduce prescribed erythropoiesis-stimulating agent ( ESA ) use and maintain hemoglobin in hemodialysis patients . This 9-month , r and omized , placebo-controlled , double-blind , multicenter clinical study included 103 patients undergoing hemodialysis 3–4 times weekly . The FPC group received dialysate containing 2 μmol/l of iron . The placebo group received st and ard dialysate . A blinded central anemia management group facilitated ESA dose adjustments . Intravenous iron was administered according to the approved indication when ferritin levels fell below 200 μg/l . The primary end point was the percentage change from baseline in prescribed ESA dose at end of treatment . Secondary end points included intravenous iron use and safety . At the end of treatment , there was a significant 35 % reduction in prescribed ESA dose in FPC-treated patients compared with placebo . The FPC patients used 51 % less intravenous iron  than  placebo . Adverse and serious adverse events were similar in both groups . Thus , FPC delivered via dialysate significantly reduces the prescribed ESA dose and the amount of intravenous iron needed to maintain hemoglobin in chronic hemodialysis patients Background : In the early weeks of life , very low birth weight ( VLBW ) infants experience intense laboratory blood sampling leading to clinical ly significant anemia and the need for red blood cell transfusion . Although controversial , treatment with recombinant human erythropoietin ( EPO ) and iron has been recommended to stimulate erythropoiesis ; optimal dosing of EPO and iron is still uncertain . Objectives : To assess the validity of a four-quadrant diagnostic plot of iron availability ( ferritin index ) versus iron dem and for erythropoiesis ( reticulocyte hemoglobin content , CHr ) for differentiating iron status in anemic VLBW infants . Methods : Study subjects were enrolled in a previously reported r and omized controlled trial of clinical ly stable VLBW infants < 31 weeks ’ gestation and < 1,300 g at birth to receive 18 days of treatment with : group 1 : oral iron ; group 2 : EPO + oral iron , and group 3 : EPO + intravenous + oral iron . Results : At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group . By day 18 , CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease . Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia , respectively . Conclusions : The diagnostic plot for differentiating anemia in VLBW infants may be an informative , clinical ly useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states . Larger additional studies in difficult patient population s are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed Background Patients with chronic HCV infection have increased liver iron . Recently identified protein hepcidin synthesized in the liver , is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation . Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection . We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection . Methods Sixty patients ( 27 male , 33 female , mean age 50 ±15 years ) on chronic HD were included . Parameters related to iron metabolism ( ferritin , serum iron and total iron binding capacity ( TIBC ) ) , inflammation ( hs-CRP , TNF-α and IL-6 ) and prohepcidin levels were measured . The response to treatment ( erythropoiesis-stimulating agent ( ESA ) resistance index ) was assessed from the ratio of the weekly erythropoietin ( rhuEPO ) dose to hemoglobin ( Hb ) per unit weight . Results Serum prohepcidin levels of HCV positive patients ( 135 ± 25 ng/mL ) were significantly lower than HCV negative patients [ 148 ± 18 ng/mL , ( p = 0.025 ) ] . Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients ( p = 0.016 ) . Serum prohepcidin levels were positively correlated with ferritin ( r = 0.405 , p = 0.001 ) and IL-6 ( r = 0.271 , p = 0.050 ) levels in HD patients . In the HCV positive group , serum prohepcidin levels significantly correlated with ferritin levels ( r = 0.514 p = 0.004 ) . In the HCV negative group , serum prohepcidin levels significantly correlated with serum IL-6 levels ( r = 0.418 , p = 0.027 ) . In multiple regression analysis performed to predict prohepcidin in HCV positive patients , serum ferritin was found to be an independent variable ( r = 0.28 , p = 0.008 ) . Conclusions HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients Iron deficiency is an important cause of anemia in patients with chronic kidney disease ( CKD ) , but intravenous iron is infrequently used among patients who are not on dialysis .  Ferumoxytol is a novel intravenous iron product that can be administered as a rapid injection . This Phase III trial r and omly assigned 304 patients with CKD in a 3:1 ratio to two 510-mg doses of intravenous ferumoxytol within 5 + /- 3 d or 200 mg of elemental oral iron daily for 21 d. The increase in hemoglobin at day 35 , the primary efficacy end point , was 0.82 + /- 1.24 g/dl with ferumoxytol and 0.16 + /- 1.02 g/dl with oral iron ( P < 0.0001 ) . Among patients who were not receiving erythropoiesis-stimulating agents , hemoglobin increased 0.62 + /- 1.02 g/dl with ferumoxytol and 0.13 + /- 0.93 g/dl with oral iron . Among patients who were receiving erythropoiesis-stimulating agents , hemoglobin increased 1.16 + /- 1.49 g/dl with ferumoxytol and 0.19 + /- 1.14 g/dl with oral iron .  Treatment-related adverse events occurred in 10.6 % of patients who were treated with ferumoxytol and 24.0 % of those who were treated with oral iron ; none was serious . In summary , a regimen of two doses of 510 mg of intravenous ferumoxytol administered rapidly within 5 + /- 3 d was well tolerated and had the intended therapeutic effect . This regimen may offer a new , efficient option to treat iron deficiency anemia in patients with CKD PURPOSE Functional iron deficiency may impair response to erythropoiesis-stimulating agents ( ESAs ) in iron-replete patients with chemotherapy-associated anemia ( CAA ) . This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA . PATIENTS AND METHODS This prospect i ve , multicenter , r and omized trial enrolled 502 patients with hemoglobin ( Hb ) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies . All patients received darbepoetin alfa once every 3 weeks and were r and omly assigned to receive either ferric gluconate 187.5 mg intravenously ( IV ) every 3 weeks , oral daily ferrous sulfate 325 mg , or oral placebo for 16 weeks . RESULTS There was no difference in the erythropoietic response rate ( ie , proportion of patients achieving Hb ≥ 12 g/dL or Hb increase ≥ 2 g/dL from baseline ) : 69.5 % ( 95 % CI , 61.9 % to 76.5 % ) of IV iron-treated patients achieved an erythropoietic response compared with 66.9 % ( 95 % CI , 59.1 % to 74.0 % ) who received oral iron and 65.0 % ( 95 % CI , 57.2 % to 72.3 % ) who received oral placebo ( P = .75 ) . There were also no differences in the proportion of patients requiring red cell transfusions , changes in quality of life , or the dose of darbepoetin administered . Adverse events ( AEs ) tended to be more common in the IV iron arm : grade 3 or higher AEs occurred in 54 % ( 95 % CI , 46 % to 61 % ) of patients receiving IV iron compared with 44 % ( 95 % CI , 36 % to 52 % ) who received oral iron and 46 % ( 95 % CI , 38 % to 54 % ) who received oral placebo ( P = .16 ) . CONCLUSION In patients with CAA , addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo In patients with renal anemia , iron therapy can be administered intermittently or regularly at a low dose . We performed a r and omized clinical trial in pediatric patients with end-stage renal failure on hemodialysis and absolute or functional iron deficiency . The study group received maintenance iron therapy according to the ferritin serum levels and the control group received intermittent 10-weekly doses . Success was defined as stabilization of ferritin levels between 100 and 800 μg/l and transferrin saturation ( TSAT ) between 20 % and 50 % , in addition to an increase in the hemoglobin level . The major reason for exclusion was iron overload . The study group received 6 mg/kg per month of parenteral iron [ 95 % confidence interval ( CI ) 3.3–8.8 ] and the control group 14.4 mg/kg per month ( 95 % CI 12–16.8 ) ( P<0.001 ) . After 4 months of treatment , ferritin levels increased to 66 μg/l ( 95 % CI 69–200 ) in the study group and to 334 μg/l ( 95 % CI 145–522 ) in the control group ( P=0.009 ) . Maintenance therapy and intermittent weekly doses were successful in 73 % and 38 % , respectively . After 3 months of treatment , hemoglobin levels increased to 10 g/dl , with no difference between the groups . However , in the control group the increase in hemoglobin levels was unsustained , and 3 patients needed transfusion . Patients in the control group had a higher risk of iron overload than patients in the study group ( 70 % vs. 19 % ) . Thus , the regimen based on assessment of serum ferritin levels was more efficient than the intermittent regimen because it increased and maintained the hemoglobin levels with lower iron doses and a lower risk of iron overload BACKGROUND Blood transfusions are associated with higher postoperative morbidity and tumor recurrence rates in colorectal cancer surgery , To reduce the need for transfusions in patients with tumor-induced anemia who are not suitable for autologous blood donation , it was tested whether perisurgical erythropoietin application would be able to stimulate hematopoiesis adequately . METHODS In a double-blind r and omized study 150 IU/kg body weight erythropoietin was given subcutaneously every 2 days beginning 10 days before operation and continuing until postoperative day 2 . Twenty patients were r and omized into the erythropoietin group with three observed dropouts and 10 patients into the placebo group . RESULTS In the erythropoietin group two episodes of hypertension and one deep venous thrombosis were observed . Preoperative hemoglobin response in the erythropoietin group ( p = 0.069 ) was paralleled by a highly significant reticulocyte increase ( p = 0.0004 ) . However , frequency of blood transfusion was not different between both study groups ( erythropoietin , 1.82 + /- 0.80 units/ patient ; placebo , 1.80 + /- 0.97 units/patient ) . If iron availability was analyzed , a strong correlation between ferritin blood levels and transferrin iron saturation with hemoglobin response was observed in regression analysis ( p < 0.001 ) . CONCLUSIONS These results indicate that hematopoiesis in anemic patients with colorectal cancer can be stimulated by erythropoietin ; however , clinical efficacy is to be expected only in selected patients with high iron availability , which calls for further studies combining erythropoietin and parenteral iron application BACKGROUND AND OBJECTIVES Intravenous iron is a key component of anemia management for chronic kidney disease ( CKD ) .  Ferumoxytol is a unique intravenous iron product that can be administered as a rapid injection in doses up to 510 mg . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a r and omized , open-label , controlled , multicenter Phase 3 trial to evaluate the safety and efficacy of intravenous ferumoxytol compared with oral iron .  Anemic patients with CKD stage 5D on hemodialysis and on a stable erythropoiesis-stimulating agent regimen received either two injections of 510 mg of ferumoxytol within 7 d ( n = 114 ) or 200 mg elemental oral iron daily for 21 d ( n = 116 ) . The primary efficacy endpoint was the change in hemoglobin from baseline to day 35 . Safety was closely monitored . RESULTS Ferumoxytol result ed in a mean increase in hemoglobin of 1.02 + /- 1.13 g/dl at day 35 compared with 0.46 + /- 1.06 g/dl with oral iron ( P = 0.0002 ) . Twice as many ferumoxytol-treated patients than oral iron-treated patients achieved a > or = 1 g/dl hemoglobin increase at day 35 ( P = 0.0002 ) . There was a greater mean increase in transferrin saturation ( TSAT ) with ferumoxytol compared with oral iron at day 35 ( P < 0.0001 ) . The larger hemoglobin increase after ferumoxytol compared with oral iron at day 35 persisted after adjustment for baseline hemoglobin , TSAT , and serum ferritin . Overall adverse event rates were comparable between groups . CONCLUSIONS In patients on hemodialysis , rapid intravenous injection of 510 mg of ferumoxytol led to significantly greater hemoglobin increases compared with oral iron , with comparable tolerability
High-dose parenteral iron does not seem to be associated with higher risk of infection , all-cause mortality , increased hospitalization or increased cardiovascular events on analysis of RCTs .
Observational studies show increased risk for all-cause mortality , infections and hospitalizations that were not statistically significant and were associated with significant heterogeneity
Parental iron is used to optimize hemoglobin and enhance erythropoiesis in end-stage renal disease along with erythropoietin-stimulating agents .
Safety of iron has been debated extensively and there is no definite evidence whether parenteral iron increases the risk of infections and mortality .
We performed this meta- analysis to evaluate the incidence of infectious complications , hospitalizations and mortality with use of parenteral iron .