A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis. A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Iron therapy in the pediatric hemodialysis population. Multiple micronutrients including iron are not more effective than iron alone for improving hemoglobin and iron status of Malian school children. Comparison of oral versus intravenous iron therapy in predialysis patients of chronic renal failure receiving recombinant human erythropoietin. [Iron supplementation during erythropoietin therapy in patients on hemodialysis].
It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease (CKD). We conducted a randomized multicenter controlled trial in adult anemic, iron-deficient non-dialysis CKD (ND-CKD) patients (>or=stage 3) not receiving erythropoiesis-stimulating agents (ESAs).
                The participants were randomized to receive either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly x 4 or ferrous sulfate (oral iron) 325 mg t.i.d. x 42 days. Hemoglobin (Hgb), ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43. The primary outcome variable was change from baseline (CFB) to endpoint in Hgb values.
                Seventy-five patients were analyzed (intravenous iron n = 36, oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only significant with intravenous iron (p < 0.01). In comparison to oral iron, intravenous iron achieved greater improvements in ferritin (232.0 +/- 160.8 vs. 55.9 +/- 236.2 ng/ml, p < 0.001) and TSAT (8.3 +/- 7.5 vs. 2.9 +/- 8.8%, p = 0.007). Intravenous iron caused greater improvements in KDQoL scores than oral iron (p < 0.05). The most common side effect reported with intravenous iron was hypotension, while constipation was more common with oral iron.
                Oral and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD patients not receiving ESAs. Although in comparison to oral iron, intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life, it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost.
                Copyright (c) 2006 S. Karger AG, Basel. To explore the safety and efficacy of intravenous (IV) iron sucrose in maintenance peritoneal dialysis (PD).
                Randomized, controlled, parallel-group single-center trial.
                Blood Purification Center of Chaoyang, Beijing Capital University of Medical Science, China.
                46 patients on PD were involved in this trial. 26 patients received IV iron sucrose (200 mg iron) once per week for 4 weeks then once every other week for a further 4 weeks. The other 20 patients received oral ferrous succinate, 200 mg three times per day, for 8 weeks. Hemoglobin, hematocrit, serum ferritin (SF) level, and transferrin saturation (TSAT) were assessed at baseline and then again after 2, 4, and 8 weeks of treatment.
                There were no differences between the IV and oral groups in terms of sex, age, duration of PD, mean dialysate dosage per day, erythropoietin dosage per week, or hematological parameters at baseline. After 4 and 8 weeks of treatment, mean Hb and Hct were significantly increased in the IV group and were also significantly higher than those in the oral group. Levels of SF and TSAT were also significantly increased in the IV group, and significantly higher than in the oral group. After 8 weeks, the response rate in the IV group was 94.8%, which was significantly higher than that in the oral group. The mean erythropoietin dose was significantly lower in the IV group than in the oral group. Hb, Hct, SF, and TSAT levels were maintained between 4 and 8 weeks in the IV group despite the decrease in dose frequency. There were no adverse events with IV iron. Eight patients in the oral group had adverse gastrointestinal effects.
                IV iron sucrose is safe in PD patients. It increases Hb levels and serum iron parameters more effectively than oral iron; it is well tolerated and can permit reductions in the required dose of erythropoietin. Few studies compare oral to intravenous (IV) iron for managing anemia in patients with chronic kidney disease (CKD) not on dialysis.
                We enrolled 96 CKD anemic patients on erythropoietin in a randomized, open-label, multicenter, controlled study. Patients received 29 days of oral FeSO4 (325 mg t.i.d.) or intravenous (IV) iron sucrose (5 doses of 200 mg weekly). Assessments were made up to 14 days after the last dose. Primary endpoints were changes in hemoglobin and ferritin, and clinical success was evaluated from the percent of patients with combined endpoints of rises in hemoglobin/ferritin, hemoglobin/ferritin/TSAT, and hemoglobin/TSAT.
                There was no significant difference in hemoglobin values between IV and oral therapy. IV iron patients had greater increases in mean serum ferritin (288 ng/ml, p < 0.0001) compared to oral iron patients (-5.1 ng/ml, p = NS). IV iron patients with baseline ferritin < 100 ng/ml had a greater increase in hemoglobin (1.4 g/dl) compared to oral iron patients (0.9 g/dl) (p < 0.05). More IV iron patients (54.2%) attained hemoglobin values > 11.0 g/dl compared to oral iron patients (31.3%, p = 0.028), and met hemoglobin/ferritin (62.5%), hemoglobin/TSAT (47.9%), hemoglobin/ferritin/TSAT (43.8%), and ferritin/TSAT criteria (54.2%) than oral iron patients (0, 22.9, 0, and 0%, respectively). There were no serious side effects.
                These CKD patients had increases in both hemoglobin and ferritin following IV iron therapy, whereas those treated with oral iron had increases in hemoglobin without increases in iron stores. Iron sucrose, given weekly as 200 mg IV push over 5 min is an effective and safe anemia treatment in this population. Although iron deficiency frequently complicates anemia in patients with nondialysis-dependent CKD (ND-CKD), the comparative treatment value of IV iron infusion and oral iron supplementation has not been established.
                In a randomized, controlled multicenter trial, we compared the efficacy of iron sucrose, given as 1 g in divided IV doses over 14 days, with that of ferrous sulfate, given 325 mg orally thrice daily for 56 days in patients with ND-CKD stages 3 to 5, Hb < or =11 g/dL, TSAT < or =25%, and ferritin < or =300 ng/mL. Epoetin/darbepoetin therapy, if any, was not changed for eight weeks prior to or during the study.
                The proportion of patients achieving the primary outcome (Hb increase > or =1 g/dL) was greater in the IV iron treatment group than in the oral iron treatment group (44.3% vs. 28.0%, P= 0.0344), as was the mean increase in Hb by day 42 (0.7 vs. 0.4 g/dL, P= 0.0298). Compared to those in the IV iron group, patients in the oral iron treatment group showed a greater decline in GFR during the study (-4.40 vs. -1.45 mL/min/1.73m2, P= 0.0100). No serious adverse drug events (ADE) were seen in patients administered IV iron sucrose as 200 mg IV over two to five minutes, but drug-related hypotension, including one event considered serious, occurred in two females weighing less than 65 kg after 500 mg doses were given over four hours.
                IV iron administration using 1000 mg iron sucrose in divided doses is superior to oral iron therapy in the management of ND-CKD patients with anemia and low iron indices. We have compared the efficacy of oral to intravenous iron for the chronic maintenance of iron stores in hemodialysis patients. Fifty-two hemodialysis patients with initial serum ferritin greater than 100 ng/mL and transferrin saturation greater than 15% were randomly assigned to one of two groups: those receiving oral iron therapy (n = 32) and those receiving intravenous iron dextran (100 mg twice weekly) (n = 20). At study completion (4 months), the mean hematocrit was significantly higher in the intravenous group than in the oral iron group (34.4% +/- 0.7% v 31.8% +/- 0.4%, respectively; P < 0.05), the final mean recombinant human erythropoietin dose was 46% lower in the intravenous iron group than in the oral group (4,050 +/- 634 U/treatment v 7,563 +/- 378 U/treatment; P < 0.05), and the mean serum ferritin was significantly higher in the intravenous group than in the oral iron group (753.9 +/- 30.2 ng/mL v 157.3 +/- 15.4 ng/mL, respectively; P < 0.05). We have found that administering iron intravenously instead of orally for chronic maintenance iron supplementation in hemodialysis patients resulted in improved erythropoiesis. We hypothesize that most hemodialysis patients have inadequate iron stores for optimal erythropoiesis when currently recommended levels of ferritin and transferrin saturation are used to guide therapy, and that the chronic use of intravenous iron could reduce recombinant human erythropoietin requirements by maximizing iron stores. The improvement in erythropoiesis was accompanied, however, by an increase in iron indices to levels that could be indicative of tissue iron overload. Future studies must be performed to determine whether lower doses of intravenous iron dextran would improve erythropoiesis without causing potential organ iron overload. Iron therapy maintains iron stores and optimizes the response to recombinant human erythropoietin (r-HuEPO) in patients with end-stage renal failure. Information is limited, however, regarding the preferential route of iron administration in pediatric patients receiving hemodialysis. Therefore, we prospectively randomized 35 iron-replete patients (aged >1 to <20 years) to receive up to 16 weeks of maintenance i.v. ( n=17) or daily oral ( n=18) iron. Eligible patients had received hemodialysis for >2 months, had a baseline transferrin saturation [TSAT] >20%, and were receiving maintenance r-HuEPO. Treatment arms were evenly distributed with respect to baseline demographic and clinical characteristics, with no statistically significant differences in baseline hemoglobin (Hb), hematocrit (Hct), reticulocyte Hb content (CHr), serum ferritin (SF), TSAT, or r-HuEPO dose. In the 35 patients, i.v. iron dextran and not oral iron was associated with a significant increase (138.5 to 259.1 ng/ml, P=0.003) in SF. A comparison of the change in SF between the i.v. iron group and the oral iron group was also significant ( P=0.001). Whereas only i.v. iron was associated with a significant decrease in the dose of r-HuEPO (234.0 to 157.6 U/kg per week, P=0.046) and an increase of the CHr (29.2 to 30.1 pg, P=0.049), these changes were not significantly different from those experienced by patients in the oral iron group. In both groups, the Hct remained stable and in neither group was there a significant change in the TSAT. In summary, although both oral and i.v. iron maintained patients in an iron-replete state in this short-term study, only i.v. therapy allowed for a significant improvement in iron stores. Iron deficiency and anemia remain among the most important global public health problems facing school children. Helminth infections often peak at school age and aggravate nutritional risks. We conducted a 12-wk randomized controlled trial in 406 Malian anemic schoolchildren infected with Schistosoma hematobium to examine the effects of 2 doses of praziquantel (P) (40 mg/kg body weight), P + 60 mg/d iron (Fe), and/or a multiple micronutrient supplement (MM) that included 18 mg/d Fe. Supplements were administered to the children each school day (5 d/wk) throughout the study. Changes in hemoglobin (Hb), serum ferritin (SF), and serum transferrin receptors (s-TfR) were followed. We also examined interactions between Fe and MM supplements on Hb and SF concentrations and malaria incidence. The effects of Fe on Hb and SF concentrations were greater than the effects of P alone and MM with or without added Fe at 6 and 12 wk (P < 0.001). In all groups, s-TfR decreased at 6 and 12 wk compared with baseline. The decrease was most pronounced in the P + Fe group compared with the other 3 groups at wk 6 (P = 0.05). Fe and MM interacted negatively at wk 6 and 12 to affect Hb (beta = -0.43, 95% CI = -0.77, -0.09; P = 0.01 and beta = -0.47, 95% CI = -0.83, -0.11; P = 0.01, respectively) and SF (beta = -0.42, 95% CI = -25.60, 12.31; P < 0.001, and beta = -0.37, 95% CI = -0.63, -0.12; P = 0.004, respectively). Malaria incidence was higher in the groups treated with added Fe (relative risk: 1.66; 95% CI: 0.75, 3.67). In this context, MM with added iron were not more effective than Fe without MM. Fe supplementation of schoolchildren with 60 mg/d for anemia control should be considered carefully. To compare oral versus intravenous iron in pre-dialysis patients of chronic renal failure (CRF) receiving recombinant human erythropoietin (rHuEPO).
                The study was undertaken in 40 adult patients of chronic renal failure. The patients were randomly divided into two groups A and B of 20 patients each. Group A patients were given oral iron and group B patients were given intravenous iron. All patients in both groups were given recombinant human erythropoietin 2000 IU twice weekly subcutaneously. The study was carried for up to three months. Patients were monitored every month for renal parameters and haematological parameters which included haemoglobin, reticulocyte count and packed cell volume. Ferrokinetic studies were done at baseline and at three months.
                It was observed that haematological parameters showed significant statistical improvement in the intravenous iron group as compared to group A (oral iron group). The ferrokinetic studies revealed that serum iron, serum ferritin and transferrin saturation, decreased significantly in oral iron group, whereas significant increase was seen in group B (intravenous iron group). None of the patients developed any adverse effects because of erythropoietin or iron therapy.
                Concomitant use of intravenous iron is better than oral iron in CRF patients treated with rHuEPO. The intravenous route of iron administration may be a preferred route along with rHuEPO therapy, more so in the Indian context where prevalence of iron deficiency anaemia is fairly high. The development of secondary anaemia is a constant associated phenomenon of chronic renal failure. During its treatment by recombinant human erythropoietin (rHuEPO) erythropoiesis is accelerated and this increases demands on the supply of dietary erythropoietic precursors (Fe, pyridoxine, folic acid, vitamin B12). In particular as regards iron, frequently the dietary amount is not sufficient and supplementation is necessary. The objective of the present work is to compare oral and intravenous iron supplementation in the treatment of secondary anaemia by rHuEPO in patients with chronic renal failure treated by haemodialysis. A group of haemodialyzed patients (n = 61) treated with erythropoietin, where the serum ferritin concentration had dropped beneath 300 ng/ml, or the transferrin concentration below 0.20 was divided at random into two sub-groups. To group "A" Actiferrin was administered 3 x 1 cps/d (Ferrosi sulfas heptahydricus, corresponding to 34.5 mg elemental Fe and serine 129 mg per capsule, i.e. a total of 724.5 mg elemental Fe per week). To group "A" Ferrum-Lek was administered 1 vial per week by the i.v. route (Ferri oxidum saccharatum, corresponding to 100 mg elemental iron per week). The two groups were comparable as to the mean erythropoietin dose (50 U/kg per week) and the patients' mean age (61 years), the male/female ratio and the spectrum of basic diseases. After six weeks of treatment a comparable increase of the haematocrit and serum iron concentration was observed in both groups. As to transferrin saturation, there was a more marked increment in the intravenously supplemented group. The serum ferritin values in group "A" declined, while in group "F" they increased. After both types of iron supplementation a comparable increase of the haematocrit and serum iron concentration occurred, the iron reserves represented by serum ferritin differed however and from the long-term aspect they are in favour of intravenous iron supplementation in haemodialyzed patients treated with erythropoietin.
The included studies provide strong evidence for increased ferritin and transferrin saturation levels, together with a small increase in haemoglobin, in patients with CKD who were treated with IV iron compared with oral iron. From a limited body of evidence, we identified a significant reduction in ESA requirements in patients treated with IV iron, and found no significant difference in mortality. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient-centred outcomes are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects.