title: Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients Effect of intravenous iron sucrose in peritoneal dialysis patients who receive erythropoiesis-stimulating agents for anemia: a randomized, controlled trial. Functional iron deficiency in hemodialysis patients with high ferritin Evaluating the effectiveness of IV iron dosing for anemia management in common clinical practice: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Intravenous iron administration does not significantly increase the risk of bacteremia in chronic hemodialysis patients. The importance of iron in long-term survival of maintenance hemodialysis patients treated with epoetin-alfa and intravenous iron: analysis of 9.5 years of prospectively collected data Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients. Ferric Citrate Reduces Intravenous Iron and Erythropoiesis-Stimulating Agent Use in ESRD. Intravenous iron exposure and mortality in patients on hemodialysis. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients. Time-dependent associations between iron and mortality in hemodialysis patients. Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study. Ferric citrate controls phosphorus and delivers iron in patients on dialysis. Correction of Uremic Iron Deficiency Anemia in Hemodialyzed Patients: A Prospective Study
abstract: Background Administration of ferric pyrophosphate citrate ( FPC , Triferic ™ ) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses . FPC donates iron directly to transferrin , bypassing the reticuloendothelial system and avoiding iron sequestration . Methods Two identical Phase 3 , r and omized , placebo-controlled trials ( CRUISE 1 and 2 ) were conducted in 599 iron-replete chronic hemodialysis patients . Patients were dialyzed with dialysate containing 2 µM FPC-iron or st and ard dialysate ( placebo ) for up to 48 weeks . Oral or intravenous iron supplementation was prohibited , and doses of erythropoiesis-stimulating agents were held constant . The primary efficacy end point was the change in hemoglobin ( Hgb ) concentration from baseline to end of treatment ( EoT ) . Secondary end points included reticulocyte hemoglobin content ( CHr ) and serum ferritin . Results In both trials , Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group ( P < 0.001 , combined results ; 95 % confidence interval [ CI ] 0.2–0.6 ) . Placebo treatment result ed in significantly larger mean decreases from baseline in CHr ( −0.9 pg versus −0.4 pg , P < 0.001 ) and serum ferritin ( −133.1 µg/L versus −69.7 µg/L , P < 0.001 ) than FPC treatment . The proportions of patients with adverse and serious adverse events were similar in both treatment groups . Conclusions FPC delivered via dialysate during hemodialysis replaces iron losses , maintains Hgb concentrations , does not increase iron stores and exhibits a safety profile similar to placebo . FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients 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 Although functional iron deficiency ( FID ) may be present in hemodialysis ( HD ) patients with high serum ferritin levels ( > 800 ng/mL ) , current protocol s often preclude the use of intravenous ( IV ) iron in these patients . However , it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin ( Hb ) levels in patients with high serum ferritin . This report describes the hematologic efficacy and safety of ferric gluconate ( FG ) therapy in patients with serum ferritin > 800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31 , 2003 . Patients classified as having high ferritin levels ( serum ferritin > 800 ng/mL on at least 66 % of routine monthly measurements and transferrin saturation [ TSAT ] < 25 % on at least 1 occasion ) were stratified as follows : patients in Group I were suspected of having FID and received FG ≥250 mg IV over a 3‐month period when Hb was < 11 g/dL , and patients in Group II were thought not to have FID and received < 250 mg FG over a 3‐month period . Both groups received st and ard recombinant human erythropoietin therapy as per the unit 's protocol . Of 496 patients , 95 exhibited high ferritin and of these , 39 patients had sufficient data for analysis . Group I patients ( n=14 ) showed a significant increase in Hb levels compared with Group II ( n=25 ) . There was no increase in ferritin levels in response to iron administration . No significant differences in hospitalizations or infections were observed between groups . Hemodialysis patients with high ferritin levels may have FID , and IV iron therapy safely improves FID in some patients . A larger r and omized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted Background Anemia management protocol s in hemodialysis ( HD ) units differ conspicuously regarding optimal intravenous ( IV ) iron dosing ; consequently , patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents ( ESAs ) . Complementary to IV iron safety studies , our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb , TSAT , ferritin , and ESA dose in common clinical practice . Methods 9,471 HD patients ( 11 countries , 2009 - 2011 ) in the DOPPS , a prospect i ve cohort study , were analyzed . Associations of IV iron dose ( 3-month average , categorized as 0 , < 300 , ≥300 mg/month ) with 3-month change in Hgb , TSAT , ferritin , and ESA dose were evaluated using adjusted GEE models . Results Relative change : Monotonically positive associations between IV iron dose and Hgb , TSAT , and ferritin change , and inverse associations with ESA dose change , were observed across multiple strata of prior Hgb , TSAT , and ferritin levels . Absolute change : TSAT , ferritin , and ESA dose changes were nearest zero with IV iron < 300 mg/month , rather than 0 mg/month or ≥300 mg/month by maintenance or replacement dosing . Findings were robust to numerous sensitivity analyses . Conclusions Though residual confounding can not be ruled out in this observational study , findings suggest that IV iron dosing < 300 mg/month , as commonly seen with maintenance dosing of 100 - 200 mg/month , may be a more effective approach to support Hgb than the higher IV iron doses ( 300 - 400 mg/month ) often given in many European and North American hemodialysis clinics . Alongside studies supporting the safety of IV iron in 100 - 200 mg/month dose range , these findings help guide the rational dosing of IV iron in anemia management protocol s for everyday hemodialysis practice Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Correction of iron deficiency is critical in chronic hemodialysis patients , and intravenous administration is superior to the oral route in this goal . Recently , concern was raised that intravenous iron administration might promote infection in dialysis patients . METHODS We review ed the data from a recent prospect i ve study of 985 patients in which no link between iron therapy and bacteremia had been found . We tested the potential role of the administration route of the iron ( intravenous vs. oral ) , the weekly amount of iron administered and the administration rate on the risk for bacteremia in these patients . RESULTS were 4-fold : in multivariate analysis , neither intravenous iron administration in the whole population nor the weekly amount of iron in the subgroup of i.v . iron-treated patients were significant risk factors for bacteremia ;  iron was not given more frequently intravenously in bacteremic than in non-bacteremic patients ; among patients treated with intravenous iron , the frequency and the amount of iron administered were significantly higher in those who developed bacteremia than in those who did not ; and in patients receiving i.v . iron , there was an increased risk of bacteremia associated with concurrent administration of erythropoietin , which was not observed in patients receiving iron orally . CONCLUSION This study failed to demonstrate a significant association between intravenous iron administration and the risk of bacteremia in dialysis patients . However , there might be a slightly increased risk of bacteremia in patients given high-frequency , high-dose intravenous iron Background In patients treated by maintenance hemodialysis the relationship to survival of hemoglobin level and administered epoetin-alfa and intravenous iron is controversial . The study aim was to determine effects on patient survival of administered epoetin-alfa and intravenous iron , and of hemoglobin and variables related to iron status . Methods The patients were 1774 treated by maintenance hemodialysis in 3 dialysis units in New York , NY from January 1998 to June , 2007 . A patient-centered , coded , electronic patient record used in patient care enabled retrospective analysis of data collected prospect ively . For survival analysis , patients were censored when transplanted , transferred to hemodialysis at home or elsewhere , peritoneal dialysis . Univariate Kaplan-Meier analysis was followed by multivariate analysis with Cox 's regression , using as variables age , race , gender , major co-morbid conditions , epoetin-alfa and intravenous iron administered , and 15 laboratory tests . Results Median age was 59 years , epoetin-alfa ( interquartile range ) 18,162 ( 12,099 , 27,741 ) units/week , intravenous iron 301 ( 202 , 455 ) mg/month , survival 789 ( 354 , 1489 ) days . Median hemoglobin was 116 ( 110 , 120)g/L , transferrin saturation 29.7 ( 24.9 , 35.1)% , serum ferritin 526 ( 247 , 833 ) μg/L , serum albumin 39.0 ( 36.3 , 41.5 ) g/L. Survival was better the higher the hemoglobin , best with > 120 g/L. Epoetin-alfa  effect on survival was weak but had statistically significant interaction with intravenous iron . For intravenous iron , survival was best with 1–202 mg/month , slightly worse with 202–455 mg/month ; it was worst with no intravenous iron , only slightly better with > 455 mg/month . Survival was worst with transferrin saturation ≤ 16 % , serum ferritin ≤ 100 μg/L , best with transferrin saturation > 25 % , serum ferritin > 600 μg/L The effects of each of hemoglobin , intravenous iron , transferrin saturation , and serum ferritin on survival were independently significant and not mediated by other predictors in the model . Conclusion Long term survival of maintenance hemodialysis patients was favorably affected by a relatively high hemoglobin level , by moderate intravenous iron administration , and by indicators of iron sufficiency . It was unfavorably influenced by a low hemoglobin level , and by indicators of iron deficiency 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 Iron deficiency limits the efficacy of recombinant human erythropoietin ( rhEPO ) therapy in end-stage renal disease ( ESRD ) patients . Functional iron deficiency occurs with serum ferritin > 500 ng/ml and /or transferrin saturation ( TSAT ) of 20 to 30 % . This study examines the effects of a maintenance intravenous iron dextran ( ivID ) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30 % ( control group ) to those of 30 to 50 % ( study group ) for a period of 6 mo . Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period , during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30 % and baseline levels of hemoglobin of 9.5 to 12.0 g/dl . After the run-in period , 19 patients r and omized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo . Twenty-three patients r and omized to the study group received four to six loading doses of ivID , 100 mg each , over a 2-wk period to achieve a TSAT > 30 % followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50 % for 6 mo . Both regimens were effective in maintaining targeted hemoglobin levels . Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the  rhEPO dose needed to maintain pre study hemoglobin levels . Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml .  Epoetin dose requirements for the study group decreased by the third month and remained 40 % lower than for the control group , result ing in an overall cost savings in managing the anemia . Secondary indicators of iron-deficient erythropoiesis were also assessed . Zinc protoporphyrin did not change in either group . Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg . It is concluded that maintenance of TSAT between 30 and 50 % reduces rhEPO requirements significantly over a 6-mo period Ferric citrate ( FC ) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous ( iv ) iron and erythropoiesis-stimulating agents ( ESAs ) . We provide detailed analyses of changes in iron/hematologic parameters and  iv iron/ESA  use at time points throughout the active control period of a phase 3 international r and omized clinical trial . In all , 441 subjects were r and omized ( 292 to FC and 149 to sevelamer carbonate and /or calcium acetate [ active control ( AC ) ] ) and followed for 52 weeks . Subjects on FC had increased ferritin and transferrin saturation ( TSAT ) levels compared with subjects on AC by week 12 ( change in ferritin , 114.1±29.35 ng/ml ; P<0.001 ; change in TSAT , 8.62%±1.57 % ; P<0.001 ) . Change in TSAT plateaued at this point , whereas change in ferritin increased through week 24 , remaining relatively stable thereafter . Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks ( median [ interquartile range ] dose=12.9 [ 1.0 - 28.9 ] versus 26.8 [ 13.4 - 47.6 ] mg/wk ; P<0.001 ) , and the percentage of subjects not requiring iv iron was higher with FC ( P<0.001 ) . Cumulative ESA over 52 weeks was lower with FC than AC ( median [ interquartile range ] dose=5303 [ 2023 - 9695 ] versus 6954 [ 2664 - 12,375 ] units/wk ; P=0.04 ) . Overall , 90.3 % of subjects on FC and 89.3 % of subjects on AC experienced adverse events . In conclusion , treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks , with a safety profile similar to that of available binders BACKGROUND AND OBJECTIVES Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking , and observational studies have been limited by assessment of short-term exposure only and /or failure to assess cause-specific mortality . The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008 .  Intravenous iron dose accumulations over 1- , 3- , and 6-month rolling windows were related to all-cause , cardiovascular , and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding . RESULTS Patients in the 1-month model cohort ( n=14,078 ) were followed a median of 19 months , during which there were 27.6 % all-cause deaths , 13.5 % cardiovascular deaths , and 3 % infection-related deaths . A reduced risk of all-cause mortality with receipt of > 150 - 350 ( hazard ratio , 0.78 ; 95 % confidence interval , 0.64 to 0.95 ) or > 350 mg ( hazard ratio , 0.79 ; 95 % confidence interval , 0.62 to 0.99 ) intravenous iron compared with > 0 - 150 mg over 1 month was observed . There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality . There was a nonstatistically significant increase in infection-related mortality with receipt of > 1050 mg intravenous iron in 3 months ( hazard ratio , 1.69 ; 95 % confidence interval , 0.87 to 3.28 ) and > 2100 mg in 6 months ( hazard ratio , 1.59 ; 95 % confidence interval , 0.73 to 3.46 ) . CONCLUSIONS Among patients on incident dialysis , receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause , cardiovascular , or infection-related mortality . However , nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of > 1050 mg in 3 months or > 2100 mg in 6 months . R and omized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses 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 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 The independent association between the indices of iron stores or administered intravenous iron , both of which vary over time , and survival in patients who are on maintenance hemodialysis ( MHD ) is not clear . It was hypothesized that the observed associations between moderately high levels of three iron markers ( serum ferritin , iron , and iron saturation ratio ) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome ( MICS ) . Time-dependent Cox regression models were examined using prospect ively collected data of the 2-yr ( July 2001 to June 2003 ) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States . After time-dependent and multivariate adjustment for case mix , administered intravenous iron and erythropoietin doses , and available surrogates of MICS , serum ferritin levels between 200 and 1200 ng/ml ( reference 100 to 199 ng/ml ) , serum iron levels between 60 and 120 microg/ml ( reference 50 to 59 microg/ml ) , and iron saturation ratio between 30 and 50 % ( reference 45 to 50 % ) were associated with the lowest all-cause and cardiovascular death risks . Compared with those who did not receive intravenous iron , administered intravenous iron up to 400 mg/mo was associated with improved survival , whereas doses > 400 mg/mo tended to be associated with higher death rates . The association between serum ferritin levels > 800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS . For ascertaining whether the observed associations between moderate doses of administered intravenous iron and improved survival are causal or due to selection bias by indication , clinical trials are warranted Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation ( TSAT ) . The Dialysis Patients ' Response to IV Iron with Elevated Ferritin ( DRIVE ) trial was design ed to evaluate the efficacy of intravenous ferric gluconate in such patients . Inclusion criteria were hemoglobin < or=11 g/dl , ferritin 500 to 1200 ng/ml , TSAT < or=25 % , and epoetin dosage > or=225 IU/kg per wk or > or=22,500 IU/wk . Patients with known infections or recent significant blood loss were excluded . Participants ( n=134 ) were r and omly assigned to no iron ( control ) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions ( intravenous iron ) . At r and omization , epoetin was increased 25 % in both groups ; further dosage changes were prohibited . At 6 wk , hemoglobin increased significantly more ( P=0.028 ) in the intravenous iron group ( 1.6 + /- 1.3 g/dl ) than in the control group ( 1.1 + /- 1.4 g/dl ) . Hemoglobin response occurred faster ( P=0.035 ) and more patients responded after intravenous iron than in the control group ( P=0.041 ) . Ferritin < or=800 or > 800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group . Similarly , the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19 % . Ferritin decreased in control subjects ( -174 + /- 225 ng/ml ) and increased after intravenous iron ( 173 + /- 272 ng/ml ; P<0.001 ) . Intravenous iron result ed in a greater increase in TSAT than in control subjects ( 7.5 + /- 7.4 versus 1.8 + /- 5.2 % ; P<0.001 ) . Reticulocyte hemoglobin content fell only in control subjects , suggesting worsening iron deficiency . Administration of ferric gluconate ( 125 mg for eight treatments ) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT < or=25 % Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient . We studied ferric citrate as a phosphorus binder and iron source . In this sequential , r and omized trial , 441 subjects on dialysis were r and omized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period , in which subjects on ferric citrate who completed the active control period were rer and omized to ferric citrate or placebo . The primary analysis compared the mean change in phosphorus  between ferric citrate and placebo during the placebo control period . A sequential gatekeeping strategy controlled study -wise type 1 error for serum ferritin , transferrin saturation , and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period . Ferric citrate controlled phosphorus compared with placebo , with a mean treatment difference of -2.2±0.2 mg/dl ( mean±SEM ) ( P<0.001 ) . Active control period phosphorus was similar between ferric citrate and active control , with comparable safety profiles . Subjects on ferric citrate achieved higher mean iron parameters ( ferritin=899±488 ng/ml [ mean±SD ] ; transferrin saturation=39%±17 % ) versus subjects on active control ( ferritin=628±367 ng/ml [ mean±SD ] ; transferrin saturation=30%±12 % ; P<0.001 for both ) . Subjects on ferric citrate received less intravenous elemental iron  ( median=12.95 mg/wk ferric citrate ; 26.88 mg/wk active control ; P<0.001 ) and less erythropoietin-stimulating agent ( median epoetin-equivalent units per week : 5306 units/wk ferric citrate ; 6951 units/wk active control ; P=0.04 ) . Hemoglobin levels were statistically higher on ferric citrate . Thus , ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin 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
target: 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
background: 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 .