ferric-oxide--saccharated and Kidney-Failure--Chronic

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Hematinics; Humans; Kidney Failure, Chronic

Several studies have evidenced the association between high serum phosphorus concentrations and adverse events especially in patients on dialysis. Recent K-DIGO guidelines suggest lowering elevated phosphate levels toward the normal range. This goal should be achieved by combining dietary counseling, optimizing dialysis procedures and prescribing phosphate binders. Despite the availability of several binders, the "ideal" phosphate binder that combines high efficacy, low pills burden, minimal side effects and low cost is still not available. In clinical practice it is crucial to reach a high patient's compliance to therapy. The pill burden is the most relevant factor contributing to low compliance. This is the case of phosphate binder therapy that represents almost 50% of total pills prescribed to patients on dialysis. It has been evidenced an association between pills of phosphate binder and poor control of phosphorus and PTH. In recent years sucroferric oxyhydroxide is available as a new phosphate binder. Its peculiarity is an high phosphate binding capability that requires prescription of low number of pills per day. This characteristic has been confirmed by several randomized controlled trials. These trials have also evidenced that sucroferric oxyhydroxide may cause some gastrointestinal side effects. There is an ongoing study to confirm in "the real world" the incidence of side effects reported by controlled trials.

Topics: Chelating Agents; Chelation Therapy; Cohort Studies; Drug Combinations; Ferric Compounds; Gastrointestinal Diseases; Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Multicenter Studies as Topic; Patient Compliance; Phosphates; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Renal Dialysis; Sucrose

Iron deficiency is common in patients on chronic dialysis, and most require iron-replacement therapy. In addition to absolute iron deficiency, many patients have functional iron deficiency as shown by a suboptimal response to the use of erythropoietin-stimulating agents. Both absolute and functional iron-deficiency anemia have been shown to respond to intravenous (IV) iron replacement. Although parenteral iron is an efficacious method and superior to standard doses of oral iron in patients on hemodialysis, there are ongoing safety concerns about repeated exposure potentially enhancing infection risk and cardiovascular disease. Each IV iron product is composed of an iron core with a carbohydrate shell. The avidity of iron binding and the type of carbohydrate shell play roles in the safe maximal dose and the frequency and severity of acute infusion reactions. All IV iron products are taken up into the reticuloendothelial system where the shell is metabolized and the iron is stored within tissue ferritin or exported to circulating transferrin. IV iron can be given as large intermittent doses (loading therapy) or in smaller doses at frequent intervals (maintenance dosing regimen). Limited trial data and observational data suggest that a maintenance dosing regimen is more efficacious and possibly safer than loading therapy. There is no consensus regarding the preferred method of iron repletion in patients on peritoneal dialysis, although small studies comparing oral and parenteral iron regimens in these patients have shown the latter to be more efficacious. Use of IV iron in virtually all hemodialysis and many peritoneal dialysis patients remains the standard of care.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Hemoglobins; Humans; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Renal Dialysis; Transferrin

Iron deficiency often occurs in patients with chronic kidney disease and can be effectively treated with parenteral supplementation of iron. In these patients, prompt application of iron therapy can help to reduce the dependence of erythropoietin-stimulating agents and effectively treat anemia. Correct evaluation of iron metabolism in CKD patients can be difficult. Duration of and response to therapy should always be considered while planning parenteral supplementation of iron. The main safety aspects of parenteral iron preparations relate to their possible anaphylactic potential and the potential induction of oxidative stress due to the release of free iron. However, parenteral iron supplementation is usually safe and without major side effects. Regarding current data, none of the iron preparations is showing definitive superiority. Although uncommon, iron preparations containing dextran can lead to severe side effects, therefore these preparations appear to have an inferior safety profile. Due to limited data, a comparison of third-generation iron preparations with previous preparations is not possible. Recently, for the first time, the third generation iron preparation ferumoxytol has been directly compared to iron sucrose. From this data and others, it remains unclear whether third generation iron preparations show safety-relevant superiority.

Topics: Administration, Oral; Anaphylaxis; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Humans; Infusions, Intravenous; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Oxidative Stress; Renal Dialysis

In the review paper an issue of the administration of iron containing drugs in the treatment of anemia in non-dialyzed patients with chronic kidney disease (CKD) is presented. Iron deficiency in patients with CKD (serum ferritin concentration below 100 ng/ml, transferrin saturation below 20%) occurs in 20-70% of cases. Prevalence of iron deficiency depends on stage of CKD and patients' gender. Among causes of iron deficiency the following reasons are mentioned: blood loss through gastrointestinal tract (17-18% of patients in pre-dialysis stage show positive results of tests on occult blood), diminished absorption (uremic gastroenteropathy, administration of drugs decreasing iron absorption), decreased delivery of food (anorexia, low protein diet), infections and inflammatory state. In the course of infections and inflammatory states body iron storage may be normal, but its utilization for erythropoesis is deteriorated (functional iron deficiency). Results of randomized controlled studies indicate greater efficiency of intravenous therapy in comparison with oral route of iron administration. In practice, the main route of administration of iron-containing drugs to non-dialyzed patients with CKD remains, however, the oral one (iron sulfate, iron fumarate, hem iron) as more convenient and seldom leading to serious side effects. Intravenous iron therapy (iron dextrose, iron polymaltose, sodium-iron gluconate, iron sucrose) is required for cases with absolute deficiency of this microelement, disturbed intestinal absorption, poor tolerance of oral iron medication or its ineffectiveness from other reasons. Administration of erythropoiesis stimulating agents in predialysis period may require intravenous iron therapy because of enhanced consumption of its stores for erythropoiesis. Attention should be paid to possible nephrotoxic effects of administration of iron containing drugs (transient proteinuria, damage of renal tubules, decrease in glomerular filtration rate).

Topics: Administration, Oral; Anemia, Iron-Deficiency; Diet, Protein-Restricted; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron; Iron Metabolism Disorders; Iron, Dietary; Kidney Failure, Chronic; Risk Factors; Sex Distribution; Treatment Outcome

In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non-transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with caution but its use should not be feared whenever indicated.

Topics: Anemia; Cytokines; Endothelial Cells; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Gluconates; Hematinics; Humans; Injections, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Neutrophils

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis; Recombinant Proteins; Renal Dialysis

Anemia in premature infants can be prevented by prophylactic treatment with recombinant human erythroprotein (r-huEPO). r-HuEPO as been used for a long time in patients with end-stage renal failure. The main factor which can limit r-HuEPO efficiency is limited iron bioavailability. Adapted iron supplementation is needed when preterm infants receive r-HuEPO in order to avoid the depletion of iron stores. Oral iron supplementation is simple but indigestibility is frequent. Furthermore, the intestinal absorption and utilization of oral iron is limited. Parenteral iron supplementation is possible in infants who are very pre-term as they are parenterally fed during the first weeks of life. There are various preparations of intravenous iron with different physicochemical properties. Toxicity and side-effects of parenteral iron preparations depend on these properties. Two parenteral iron preparations are available in France: iron-saccharate (Venofer) and iron-dextrin (Maltofer). Iron delivery and possible side-effects of these preparations are different and need to be considered before use in preterm infants.

Topics: Adult; Dietary Supplements; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Kidney Failure, Chronic; Recombinant Proteins

Absolute and functional iron deficiency is the most common cause of epoetin (recombinant human erythropoietin) hyporesponsiveness in renal failure patients. Diagnostic procedures for determining iron deficiency include measurement of serum iron levels, serum ferritin levels, saturation of transferrin and percentage of hypochromic red blood cells. Patients with iron deficiency should receive supplemental iron, either orally or intravenously. Adequate intravenous iron supplementation allows reduction of epoetin dosage by approximately 40%. Intravenous iron supplementation is recommended for all patients undergoing haemodialysis and for pre-dialysis and peritoneal dialysis patients with severe iron deficiency. During the maintenance phase (period of epoetin therapy after correction of iron deficiency), the use of low-dose intravenous iron supplementation (10 to 20 mg per haemodialysis treatment or 100 mg every second week) avoids iron overtreatment and minimises potential adverse effects. Depending on the degree of pre-existing iron deficiency, markedly higher iron doses are necessary during the correction phase (period of epoetin therapy after correction of iron deficiency) [e.g. intravenous iron 40 to 100 mg per haemodialysis session up to a total dose of 1000 mg]. The iron status should be monitored monthly during the correction phase and every 3 months during the maintenance phase to avoid overtreatment with intravenous iron.

Topics: Anemia, Iron-Deficiency; Citric Acid; Drug Combinations; Drug Monitoring; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Glucaric Acid; Humans; Infusions, Intravenous; Injections, Intravenous; Iron Compounds; Iron Overload; Iron-Dextran Complex; Kidney Failure, Chronic; Sorbitol

Intravenous iron is a standard treatment for patients undergoing hemodialysis, but comparative data regarding clinically effective regimens are limited.. In a multicenter, open-label trial with blinded end-point evaluation, we randomly assigned adults undergoing maintenance hemodialysis to receive either high-dose iron sucrose, administered intravenously in a proactive fashion (400 mg monthly, unless the ferritin concentration was >700 μg per liter or the transferrin saturation was ≥40%), or low-dose iron sucrose, administered intravenously in a reactive fashion (0 to 400 mg monthly, with a ferritin concentration of <200 μg per liter or a transferrin saturation of <20% being a trigger for iron administration). The primary end point was the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed in a time-to-first-event analysis. These end points were also analyzed as recurrent events. Other secondary end points included death, infection rate, and dose of an erythropoiesis-stimulating agent. Noninferiority of the high-dose group to the low-dose group would be established if the upper boundary of the 95% confidence interval for the hazard ratio for the primary end point did not cross 1.25.. A total of 2141 patients underwent randomization (1093 patients to the high-dose group and 1048 to the low-dose group). The median follow-up was 2.1 years. Patients in the high-dose group received a median monthly iron dose of 264 mg (interquartile range [25th to 75th percentile], 200 to 336), as compared with 145 mg (interquartile range, 100 to 190) in the low-dose group. The median monthly dose of an erythropoiesis-stimulating agent was 29,757 IU in the high-dose group and 38,805 IU in the low-dose group (median difference, -7539 IU; 95% confidence interval [CI], -9485 to -5582). A total of 320 patients (29.3%) in the high-dose group had a primary end-point event, as compared with 338 (32.3%) in the low-dose group (hazard ratio, 0.85; 95% CI, 0.73 to 1.00; P<0.001 for noninferiority; P=0.04 for superiority). In an analysis that used a recurrent-events approach, there were 429 events in the high-dose group and 507 in the low-dose group (rate ratio, 0.77; 95% CI, 0.66 to 0.92). The infection rate was the same in the two groups.. Among patients undergoing hemodialysis, a high-dose intravenous iron regimen administered proactively was superior to a low-dose regimen administered reactively and resulted in lower doses of erythropoiesis-stimulating agent being administered. (Funded by Kidney Research UK; PIVOTAL EudraCT number, 2013-002267-25 .).

Topics: Administration, Intravenous; Adult; Aged; Anemia; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Ferric Oxide, Saccharated; Ferritins; Follow-Up Studies; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Single-Blind Method; Transferrin

Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown.. PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin < 400 µg/L and transferrin saturation (TSAT) levels < 30% receiving erythropoiesis-stimulating agents (ESA) were eligible. Enrolled patients were randomized to a proactive, high-dose IV iron arm (iron sucrose 400 mg/month unless ferritin > 700 µg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 µg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years.. Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry.. PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice.. EudraCT number: 2013-002267-25.

Topics: Administration, Intravenous; Aged; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Female; Ferric Oxide, Saccharated; Ferritins; Follow-Up Studies; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Thrombosis; Treatment Outcome

Iron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis.. The Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An "oxidative stress" substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months.. FACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon.. ClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Heart; Hematinics; Humans; Kidney Failure, Chronic; Liver; Magnetic Resonance Imaging; Pancreas; Renal Dialysis

The objective of this article was to assess the safety and efficacy of long-term administration of PA21.. Phase III, open-label, long-term study in 15 sites in Japan.. Japanese hemodialysis patients (N = 161) with hyperphosphatemia aged ≥20 years undergoing stable maintenance hemodialysis 3 times weekly, for ≥12 weeks.. After a 2-week observation period with their previous hyperphosphatemia therapy, patients began the 52-week treatment with PA21, which was administered orally at an initial dose of 250 mg, 3 times daily, immediately before every meal (dosing range between 750 and 3,000 mg/day).. Safety was evaluated based on the development of adverse events and adverse drug reactions (ADRs). Efficacy was evaluated according to serum phosphorus concentration, corrected serum calcium concentration, and serum intact-parathyroid hormone concentration.. The mean serum phosphorus concentration decreased from 5.46 ± 1.06 mg/dL at baseline to 5.00 ± 1.17 mg/dL at end of treatment. The serum phosphorus concentration was maintained within the target range (3.5-6.0 mg/dL) throughout the 52 weeks of the study period with a mean of 3.3 tablets per day of PA21. Most ADRs were mild, transient, and developed early during treatment, and the incidence was not shown to increase with long-term treatment. The most frequently reported ADR was diarrhea (22.4%).. Treatment with PA21 was effective in lowering and maintaining target serum phosphorus concentrations in Japanese hemodialysis patients with hyperphosphatemia over 52 weeks. PA21 was generally well tolerated in the long term.

Topics: Aged; Asian People; Drug Combinations; Female; Ferric Compounds; Humans; Hyperphosphatemia; Japan; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Renal Dialysis; Sucrose; Treatment Outcome

Intravenous (IV) iron supplementation is widely used in hemodialysis (HD) patients to treat their periodic losses. However, the ideal dose and frequency is unknown. The goal of the study is to see if a 20 mg dose of iron IV at the end of each session of HD as iron maintenance is better than the iron prior therapy. We analyze the erythropoiesis activity (EA) and functional iron (FI) after four weeks of treatment.. In 36 patients, we measure reticulocyte count and content of hemoglobin reticulocyte (CHr) as EA and FI markers, respectively, before and after the treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy.. Reticulocyte count: 49.7 ± 23.8 × 10(3) before and 47.2 ± 17.2 × 10(3) after the treatment (p= 0.51). The CHr: 34.8 ± 3.7 pg and 34.4 ± 3.5 pg, respectively, (p= 0.35), showing an excellent correlation with the other FI markers (serum iron r = 0.6; p = 0.001; saturation transferrin r = 0.49; p = 0.004); that is not shown with the serum ferritin (r = 0.23; p = 0.192) or the hepcidin levels (r = 0.22; p = 0.251). There was not a correlation between the C-Reactive Protein, reticulocyte count, and CHr. The 13 patients who did not receive the iron prior to the study showed high FI levels, but not an increased of the serum ferritin or the serum hepcidin levels.. The administration of a small quantity of iron at the end of every HD session keeps the EA and the FI levels and allows reducing the iron overload administered and/or decreasing the iron stores markers in some patients.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Erythropoiesis; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Hepcidins; Humans; Kidney Failure, Chronic; Maintenance Chemotherapy; Male; Renal Dialysis; Reticulocyte Count; Reticulocytes; Transferrin

Reticuloendothelial blockade in hemodialysis patients prevents optimal intravenous (IV) iron utilization. Vitamin C has emerged as a potential therapy to improve anemia treatment by enhancing iron mobilization. However, Vitamin C can act as a pro-oxidant in the presence of iron. This was a prospective, open-label, crossover study. Thirteen patients with end-stage renal disease on hemodialysis and four healthy controls were assigned to receive 100 mg of IV iron sucrose (IS) or 100 mg of IV IS co-administered with 300 mg of IV Vitamin C (IS + C) in random sequence. Serum samples for IL-1, IL-6, TNF-α and IL-10 and non-transferrin bound iron were obtained at baseline, 45 min and 105 min post study medication administration. Peripheral blood mononuclear cells were isolated at the same time points and stained with fluorescent probes to identify intracellular reactive oxygen species and mitochondrial membrane potential (Δψm) by flow cytometry. Lipid peroxidation was assessed by plasma F2-isoprosatane concentration. Both IS and IS + C were associated with increased plasma F2-isoprostanes concentrations post-infusion. Maximal plasma F2-isoprostane concentrations after IS + C were significantly elevated from baseline (234 ± 0.04 vs. 0.198 ± 0.028 ng/mL, p = 0.02). After IS + C, IL-1, IL-6, IL-10, and TNF-alpha were significantly elevated compared to baseline. After IS alone only IL-6 was noted to be elevated. Intracellular production of H(2)O(2) and loss of mitochondrial membrane potential (Δψm) was observed after IS while IS + C was associated with increased O (2) (·-) production. Both IS and IS + C induced serum cytokine activation accompanied by lipid peroxidation, however, IS + C induced higher plasma concentrations of F2-isoprostanes, IL-1, IL-10, and TNF-α post-infusion. Long-term safety studies of IV iron co-administered with Vitamin C are warranted.

Topics: Adult; Ascorbic Acid; Cross-Over Studies; Cytokines; Epoetin Alfa; Erythropoietin; F2-Isoprostanes; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Lipid Peroxidation; Male; Membrane Potential, Mitochondrial; Middle Aged; Oxidative Stress; Prospective Studies; Reactive Oxygen Species; Recombinant Proteins; Systems Biology

To investigate the effect of different intravenous iron treatment regimens on anemia and oxidative stress in maintenance hemodialysis (MHD) patients.. A total of 58 MHD patients were randomly divided into a multi-frequency low-dose intravenous iron group (iron sucrose 25 mg, twice a week for 8 weeks, n=19), a less-frequency regular-dose intravenous iron group (iron sucrose 100 mg, once every two weeks for 8 weeks, n=19), and a non-iron group (n=20). Another 20 healthy people served as a control group (n=20). The changes of hemoglobin (Hb), hematocrit (HCT), serum ferritin (SF) and transferrin saturation (TSAT), as well as the oxidative stress parameters of malon-dialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were detected before and after the treatment.. After 8 weeks, compared with the non-iron group, the levels of Hb, HCT, SF and TSAT in the two iron groups were significantly elevated (P<0.01), but there was no difference between the two iron groups (P>0.05). After the single dialysis, the two iron groups had higher level of serum MDA, MPO and lower level of serum SOD than that of the non-iron supplementation group (P<0.01). The multi-frequency low-dose intravenous iron group had lower level of serum MDA [(5.37 ± 0.73) nmol/mL vs (6.37±1.67) nmol/mL], MPO [(81.41±7.60) U/L vs (96.75±16.97) U/L] and higher level of serum SOD [(84.77 ± 14.02) U/mL vs (68.23 ± 4.90) U/mL] than that of the less-frequency regular-dose intravenous iron group. After 8 weeks, there was no significant difference between the two iron groups (P>0.05).. Multi-frequency low-dose intravenous iron can effectively improve anemia in MHD patients, whose acute oxidative stress is lower than that of less-frequency regular-dose intravenous iron, and is a relatively safe and effective intravenous iron treatment regimen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Sucrose; Young Adult

Most dialysis patients receiving erythropoesis-stimulating agents (ESA) also receive parenteral iron supplementation. There are few data on the risk of hemosiderosis in this setting.. We prospectively measured liver iron concentration by means of T1 and T2* contrast magnetic resonance imaging (MRI) without gadolinium, in a cohort of 119 fit hemodialysis patients receiving both parenteral iron and ESA, in keeping with current guidelines.. Mild to severe hepatic iron overload was observed in 100 patients (84%; confidence interval, [CI] 76%-90%), of whom 36% (CI, 27%-46%) had severe hepatic iron overload (liver iron concentration >201 μmol/g of dry weight). In the cross-sectional study, infused iron, hepcidin, and C-reactive protein values correlated with hepatic iron stores in both univariate analysis (P<.05, Spearman test) and binary logistic regression (P <.05). In 11 patients who were monitored closely during parenteral iron therapy, the iron dose infused per month correlated strongly with both the overall increase and the monthly increase in liver iron concentration (respectively, rho=0.66, P=.0306 and rho=0.85, P=0.0015, Spearman test). In the 33 patients with iron overload, iron stores fell significantly after iron withdrawal or after a major reduction in the iron dose (first MRI: 220 μmol/g (range: 60-340); last MRI: 50 μmol/g (range: 5-210); P <.0001, Wilcoxon's paired test).. Most hemodialysis patients receiving ESA and intravenous iron supplementation have hepatic iron overload on MRI. These findings call for a revision of guidelines on iron therapy in this setting, especially regarding the amount of iron infused and noninvasive methods for monitoring iron stores.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Cross-Sectional Studies; Drug Therapy, Combination; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemosiderosis; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Liver; Logistic Models; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Renal Dialysis

The relative safety of parenteral iron preparations is a controversial issue in the management of anemia in chronic kidney disease (CKD), as direct head-to-head comparative trials are lacking. In this study, patients of CKD were randomized to receive intravenous low molecular weight iron dextran (ID), sodium ferrigluconate complex (SFGC), and iron sucrose (IS) at doses and infusion rates recommended by the product manufacturer. One time test dose was used only for ID and SFGC. A total of 2,980 injections (n = 339) of i.v. iron was given, and 49 patients (14.45% per patient) and a total of 56 adverse events (1.88% per infusion) were noted. Odds ratios (OR) of serious adverse drug events (ADE; i.e., death, anaphylaxis, or suspected immuno-allergic events) per patient was not significant between ID vs. SFGC (3.566) and SFGC vs. IS (2.129), whereas that between ID vs. IS (7.594) was highly significant (p = 0.034). OR of serious ADE exposure was significantly higher in ID vs. SFGC (OR = 5.670, p = 0.0147) and ID vs. IS (OR = 7.799, p < 0.001). No significant difference was seen between the three groups in terms of non-serious ADEs. Drug discontinuation occurred significantly more often with ID. One patient who developed anaphylactoid reaction with SFGC and ID tolerated iron sucrose well.

Topics: Adult; Age Factors; Analysis of Variance; Anemia, Iron-Deficiency; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Predictive Value of Tests; Probability; Renal Dialysis; Risk Assessment; Severity of Illness Index; Sex Factors; Treatment Outcome

Anaemia is a common in chronic kidney disease. Although erythropoietin and iron supplementation are established treatments, knowledge on the use of IV iron alone in patients not on dialysis or erythropoietin is incomplete. The responses of 82 patients referred to the renal anaemia service with haemoglobin of 11.5 g/dl or less were assessed 1 week after completing four once weekly doses of 200 mg of venofer. No patients were on dialysis or erythropoietin. The haemoglobin rise 1 week after treatment was 0.53 g/dl. Ferritin levels improved from 110.8 to 410.2 ng/l and transferrin saturation from 17.7 to 27.3%. Ferritin levels remained below our target range (200-500 ng/l) in 7.7% while 25.6% had levels above this. Ferritin levels remained less than 800 ng/l in nearly all patients. Intravenous iron is cost effective and should be considered for use in patients with renal anaemia. Patients with CKD stage 5 appeared to respond less well.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Cost-Benefit Analysis; Drug Administration Schedule; Drug Monitoring; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glomerular Filtration Rate; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Severity of Illness Index; Sucrose; Transferrin; Treatment Outcome

Renal anemia is one of the commonest complications of chronic renal failure. Iron deficiency is the most common factor which affects the efficacy of recombinant human erythropoietin (EPO) therapy. Intravenous (i.v.) iron preparations are commonly used in Western countries, but iron sucrose is seldom used in Chinese patients on maintenance hemodialysis. The aim of the present study was to explore the safety and efficacy of i.v. iron sucrose in Chinese patients on maintenance hemodialysis and to explore the optimal administration frequency.. One hundred and thirty-six patients on maintenance hemodialysis were involved in this randomized, controlled, parallel-group, single-center trial. Seventy patients received i.v. iron sucrose (Venofer(R), delivering 100 mg iron) twice a week for 8 weeks, then once a week for another 4 weeks. The other 66 patients received oral (p.o.) ferrous succinate 200 mg t.i.d. for 12 weeks. Levels of serum ferritin (SF), transferrin saturation (TSAT), hemoglobin (Hb) and hematocrit (Hct) were assessed at baseline and then again after 4, 8 and 12 weeks of treatment.. There were no differences between i.v. and p.o. groups in terms of sex, age, duration of hemodialysis, dialysis frequency per week, EPO dosage per week, the level of intact parathyroid hormone, serum creatinine, blood urea nitrogen, or hematological parameters at baseline. After 8 and 12 weeks of treatment, mean Hb concentration and Hct were significantly increased in the i.v. group, and were also significantly higher than those in the p.o. group. Levels of SF and TSAT were also significantly increased in the i.v. group, and significantly higher than in the p.o. group. After 8 weeks, the response rate in the i.v. group was 88.6%, which was significantly higher than that in the p.o. group. The mean EPO dose was significantly lower in the i.v. group than the p.o. group. Hb, Hct, SF and TSAT levels were maintained between 8 and 12 weeks in the i.v. group despite the decrease in dose frequency. There were no adverse events related to i.v. iron administration. Twenty-two patients in the p.o. group had adverse gastrointestinal effects. After 12 weeks, the cost of EPO + i.v. iron was significantly higher than the cost of EPO + p.o. iron.. Intravenous iron sucrose can effectively increase serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and is well tolerated. Infusion of i.v. iron sucrose 100 mg per week can maintain serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and can permit reductions in the required dose of EPO. However, the total cost of i.v. iron is relatively high.

Topics: Adult; Aged; Anemia; China; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Glucaric Acid; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Treatment Outcome

To compare non-transferrin-bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose.. Prospective, open-label, crossover study.. University-affiliated general clinical research center.. Twelve ambulatory patients undergoing hemodialysis.. Patients received 100 mg of intravenous iron dextran, sodium ferric gluconate, and iron sucrose in random sequence, with a 2-week washout period between treatments.. Serum samples for transferrin saturation, non-transferrin-bound iron, and malondialdehyde (MDA; marker of lipid peroxidation) were obtained before (baseline) and 30, 60, 120, and 360 minutes and 2 weeks after each iron infusion. A serum sample for hemeoxygenase-1 (HO-1) RNA was obtained at baseline and 360 minutes after infusion. Non-transferrin-bound iron values were significantly higher 30 minutes after administration of sodium ferric gluconate and iron sucrose compared with iron dextran (mean +/- SEM 10.1 +/- 2.2, 3.8 +/- 0.8, and 0.23 +/-0.1 microM, respectively, p<0.001 for sodium ferric gluconate vs iron dextran, p = 0.002 for iron sucrose vs iron dextran). A significant positive correlation was noted between transferrin saturation and the presence of non-transferrin-bound iron for sodium ferric gluconate and iron sucrose (r2 = 0.37 and 0.45, respectively, p<0.001) but not for iron dextran (r2 = 0.09). After sodium ferric gluconate, significantly more samples showed increases in MDA levels from baseline compared with iron sucrose and iron dextran (p = 0.006); these increased levels were associated with the presence of non-transferrin-bound iron, baseline transferrin saturation above 30%, baseline transferrin levels below 180 mg/dl, and ferritin levels above 500 ng/ml (p<0.05). However, only a transferrin level below 180 mg/dl was independently associated (odds ratio 4.8, 95% confidence interval 1.2-15.3).. Iron sucrose and sodium ferric gluconate were associated with greater non-transferrin-bound iron appearance compared with iron dextran. However, only sodium ferric gluconate showed significant increases in lipid peroxidation. The relationship between non-transferrin-bound iron from intravenous iron and oxidative stress warrants further exploration.

Topics: Biomarkers; Cross-Over Studies; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Prospective Studies; Renal Dialysis

1. Patients with advanced chronic renal disease and anaemia have decreased serum paraoxonase-1 (PON1) activity and an increased degree of oxidative stress compared with normal subjects. The present study investigated the effects of treatment of anaemia with exogenous recombinant erythropoietin (EPO) beta and iron on levels of antibodies against oxidized low-density lipoproteins (ox-LDL), as well as on serum PON1 activity and concentration, in predialysis patients with chronic renal disease. 2. Forty-nine patients with chronic renal failure and haemoglobin (Hb) < 11 g/dL were treated over a period of 6 months with EPObeta (80-120 U/kg per week, s.c.) and variable doses of iron. Selected biochemical variables were determined before and after treatment. 3. Treatment with EPObeta and iron was associated with a significant increase in mean (+/-SD) blood Hb concentration compared with pretreatment values (12.8 +/- 1.5 vs 9.9 +/- 0.6 g/dL, respectively; P < 0.001). The average dose of EPObeta was 6160 +/- 3000 U/week. After 6 months of treatment, compared with pretreatment values, the median levels (95% confidence intervals) of antibodies against ox-LDL were decreased (17.5 (10.6-24.4) vs 24.8 (11.5-38.1) U/mL, respectively; P < 0.001), serum PON1 activity was slightly but significantly increased (123.6 (76.1-343.6) vs 101.0 (50.0-332.5) U/L, respectively; P = 0.016) and the concentration of PON1 was significantly decreased (37.3 (11.8-76.2) vs 46.7 (24.6-98.0) mg/L, respectively; P < 0.001). There were no significant changes in total cholesterol, triglycerides or cholesterol fraction concentrations before and after treatment. 4. We suggest that EPObeta and iron treatment of anaemia promotes significant changes in serum PON1 activity and concentration and has a beneficial effect on oxidative stress in predialysis patients with chronic renal disease.

Topics: Aged; Anemia; Antibodies; Aryldialkylphosphatase; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Lipid Peroxidation; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Recombinant Proteins; Renal Dialysis; Treatment Outcome

The objectives of the present trial were to compare the side effects and safety of two intravenous iron preparations (iron-dextran, iron-sucrose) in patients with end stage renal disease.. A total of 60 patients were randomized and assigned to one of two treatment groups (iron-dextran, n = 30; iron-sucrose, n = 30). A standard test dose of 25 mg of low molecular weight iron-dextran and iron-sucrose were administered over 15 minutes during the initial visit, monitoring very closely for adverse reactions. If this dose was well tolerated, 75 mg of iron diluted in 100 mL of normal saline was administered over 30 minutes. Adverse reactions were recorded.. The mean age of the patients was 51.5+/-17.4 years (range, 21 to 80 years). Of the 30 patients who received low molecular weight iron-dextran, 11 developed side effects (pruritus, 1 patient; wheezing, 1 patient; chest pain, 1 patient; nausea, 4 patients; hypotension, 1 patient; swelling, 1 patient; headache, 2 patients). Of the 30 patients who received iron-sucrose, 13 developed side effects (pruritus, 1 patient; wheezing, 1 patient; diarrhea, 1 patient; nausea, 4 patients; hypotension, 2 patients; swelling, 1 patient; headache, 3 patients). Adverse events occurred with similar frequency in the two treatment groups in our study (p > 0.05). We did not observe any serious reactions in the two groups.. We conclude that the incidence of side effects associated with iron-dextran was not different than that of iron-sucrose in our study. Large scale randomized studies are needed to compare the full side effect profile of intravenous iron preparations more precisely.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intra-Arterial; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged

Topics: Adult; Aged; Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Treatment Outcome

Fast intravenous (i.v.) iron administration during hemodialysis (HD) is associated with the augmentation of oxidative stress and the increase in inflammatory biomarkers, which are also induced by the hemodialysis procedure itself. The aim of this study was to investigate if slow i.v. iron administration would aggravate the status of oxidative stress and inflammatory biomarkers during a hemodialysis session.. Twenty dialysis patients 30-92 years of age that were iron replete and had values for hemoglobin, transferrin saturation and serum ferritin among recommended goals were evaluated in three separate hemodialysis sessions. In the first session patients did not receive any iron treatment, whereas during the second and the third session patients received slow (60 min) i.v. infusions of 100 mg of iron sucrose and 100 mg of iron dextran, respectively. Blood samples were drawn before the hemodialysis session, 15 min after the end of iron administration and at the end of the hemodialysis session in all occasions, for the measurement of markers of oxidant stress (oxidized LDL and ischemia-modified albumin) and inflammation (high-sensitivity C-reactive protein, interleukin-6 and tumor necrosis factor-alpha).. Oxidized LDL was not significantly altered during hemodialysis and this pattern was similar between the three occasions studied. In contrast, ischemia-modified albumin was significantly increased and this effect was also not different between the net hemodialysis and the occasions of iron administration. High-sensitivity CRP, IL-6 and TNF-alpha were all significantly elevated during hemodialysis and again both types of iron administration did not produce significant changes in this pattern.. We did not find an increase in the markers of oxidation/inflammation studied, after slow i.v. iron administration during hemodialysis session.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Biomarkers; C-Reactive Protein; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Inflammation Mediators; Infusions, Intravenous; Interleukin-6; Iron-Dextran Complex; Kidney Failure, Chronic; Lipoproteins, LDL; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Serum Albumin; Tumor Necrosis Factor-alpha

Anemia in hemodialysis patients is a complex syndrome. The impetus of this study was to assess the safety and efficacy of iron saccharate complex (ISC) and sodium ferric gluconate complex (SFGC) in treating anemia in hemodialysis patients.. Forty-eight adult anemic patients of both genders (33 males and 15 females) who had an adequate level of both hemodialysis and nutrition status and received neither EPO nor parenteral iron therapy during the preceding 6 months were randomized to 2 groups. The first group comprised 22 patients who were treated with parenteral ISC, 100 mg twice weekly for 2 months and once weekly thereafter. The second group included 26 patients who received SFGC, 62.5 mg twice weekly for 2 months and once weekly thereafter. The patients were followed up for 6 months.. This head-to-head study showed that iron stores were adequately repleted by the use of both drugs. Repletion of iron stores was associated with a significant rise in both hemoglobin and hematocrit in both groups at the end of the follow-up period in comparison to their initial values at the start of the study (p < 0.001). Both parenteral iron therapy preparations were tolerated without a statistical difference between both groups.. This head-to-head study confirmed that both parenteral iron preparations are effective for adequate repletion of iron stores and constituted a step forward in the management of anemic hemodialysis patients without noticeable adverse effects related to the administration of both iron preparations.

Topics: Adult; Anemia, Iron-Deficiency; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Gluconates; Humans; Kidney Failure, Chronic; Male; Parenteral Nutrition; Renal Dialysis

There are concerns about adverse vascular effects of intravenous iron by inducing oxidative stress. We therefore examined the effect of a single high dose of intravenous iron on endothelial function and biochemical markers of iron homeostasis.. In a randomized, placebo-controlled, double-blind, parallel-group study, forearm blood flow (FBF) was assessed by strain-gauge plethysmography in 38 peritoneal dialysis patients before and after a single intravenous infusion of 300 mg iron sucrose.. Iron infusion increased total (Delta 601 microg/100 mL, CI 507, 696) and non-transferrin-bound iron (Delta 237.2 micromol/L, CI 173.6, 300.8) approximately 10-fold, as well as redox-active iron nearly five-fold (Delta 0.76 micromol/L, CI 0.54, 0.98). After iron infusion basal FBF was 59% higher than after placebo. FBF response to acetylcholine before and after iron infusion was 263 +/- 32% and 310 +/- 33%, corresponding to 304 +/- 43% and 373 +/- 29% in the placebo group, respectively. Before and after iron or placebo infusion, glyceryl-trinitrate increased resting FBF to 232 +/- 22% and 258 +/- 21% in the iron group, and to 234 +/- 18% and 270 +/- 30% in the placebo group. L-N-monomethyl-arginine decreased FBF to 70 +/- 4% and 72 +/- 3% before and after iron, and to 74 +/- 4% and 73 +/- 4% before and after placebo infusions, respectively. Despite higher basal FBF after iron infusion, absolute and relative FBF changes in response to vasoactive substances were not significantly different between iron and placebo groups.. Our data suggest that 300 mg intravenous iron sucrose has a vasodilatory effect, but does not impair vascular reactivity in dialysis patients, despite a significant increase in non-transferrin-bound and redox-active iron.

Topics: Adult; Aged; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Forearm; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Peritoneal Dialysis; Prospective Studies; Regional Blood Flow; Vasodilation

Parenteral iron replacement and maintenance are frequently required in hemodialysis patients. However, serious adverse events have been reported after single doses of some intravenous iron products. This multicenter phase IV clinical trial examined the safety of iron sucrose for the treatment of iron deficiency and for the maintenance of iron sufficiency in hemodialysis patients.. In this safety study, iron sucrose was given in two dosing regimens. Iron deficient patients were treated with intravenous iron sucrose, 100 mg, during 10 consecutive hemodialysis sessions (replacement regimen). Iron replete patients were given iron sucrose, 100 mg intravenous (iv) over 5 minutes, weekly for 10 weeks (maintenance regimen). At the end of each 10-dose cycle, iron status was reassessed, and dosing during the subsequent cycle was based on the adequacy of iron stores as per Dialysis Outcome Quality Initiative (K/DOQI) Guidelines. With each dosing regimen, adverse events, if any, were recorded and described.. Six hundred and sixty-five hemodialysis patients, including 80 who had experienced previous intolerance to other parenteral iron preparations, received a total of 8583 doses of iron sucrose. One hundred eighty-eight patients received more than one iv iron cycle (replacement, maintenance, or both). There were no serious or life-threatening drug-related adverse events.. Iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Drug Hypersensitivity; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Sepsis

Almost all hemodialysis (HD) patients require intravenous iron therapy to correct their anemia and maintain their iron stores. Sodium ferric gluconate complex (SFGC) is approved by the Food and Drug Administration (FDA) for treatment of iron deficiency anemia in HD patients at individual doses up to 125 mg over 10 minutes (12.5 mg/min) and has been shown to have a superior safety profile compared with iron-dextran. Higher individual doses of SFGC would permit more rapid repletion of iron stores and greater flexibility in maintenance iron therapy as well as simplify treatment of peritoneal dialysis patients and chronic kidney disease patients.. The authors reviewed the safety and tolerability of higher-dose SFGC infusions (> or =250 mg) in 144 HD patients who were previously tolerant to a single 125-mg dose of SFGC. These 144 patients received a total of 590 doses of > or =250 mg of SFGC; 571 doses were 250 mg SFGC, and most of these were infused over 1 hour, an infusion rate of 4.17 mg/min. The other 19 doses were 312.5 mg (n = 1), 375 mg (n = 14), and 500 mg (n = 4). Infusion rates varied from 1.22 mg/min to 25.0 mg/min.. Only one patient was considered intolerant to higher-dosing SFGC after having pruritus after a second 250-mg dose of SFGC. Three patients had nonserious events that did not preclude further dosing of SFGC.. Administration of 250 mg SFGC over 1 hour is safe and well tolerated. Individual doses of 375 mg and 500 mg SFGC also were well tolerated, but further research and experience are needed to confirm the safety and tolerance of these doses.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Population Surveillance; Treatment Outcome

It is well known that free iron causes oxidant stress to increase. However data concerning whether intravenously (I.V) administered iron in maintenance doses (10-20 mg) gives rise to increased oxidant stress and disturbed erythrocyte deformability (EDEF) in hemodialysis (HD) patients is lacking. In the present study, we aimed to evaluate and compare the effects of I.V iron on oxidant stress and EDEF.. Thirteen HD patients (10 males, 3 females, mean age: 49.9 +/- 13.4 years), given I.V iron were included in the study. All patients were undergone three consecutive HD session. The first HD session was performed without iron administration (Group 1), whereas in the following sessions the same patients were given 20 mg (Group 2) and 100 mg (Group 3) iron III hydroxide sucrose (Venofer--Abdi Ibrahim) I.V at the end of the dialysis session. In study periods, 7 blood samples were drawn from each patient: before dialysis, at the end of the dialysis (just after the session), 15, 30, 60, 90 and 120 minutes after each dialysis session. However 15 minute samples were not drawn in the third group, since I.V iron was given by infusion in 30 minutes. EDEF and plasma malondialdehyde (MDA) were studied in all samples.. When the results of the session without iron were considered, bivariate correlation analysis did not reveal any correlation between MDA and EDEF. When the course of each parameter were considered separately, MDA levels 90 and 120 minutes after HD session were significantly higher than that of the before and just after the HD session (p < 0.05). Whereas EDEF in 60, 90 and 120 minutes after HD session was found to be worsened when compared to before and just after HD sessions' values (p < 0.05). When results of the session with 20 mg iron were considered, EDEF and MDA values were not found to be correlated and throughout the course. Although EDEF did not present any significant change, MDA levels 60, 90 and 120 minutes after HD session were found to be significantly higher than that of the 15 and 30 minutes after HD session (p < 0,05). When results of the session with 100 mg iron were considered, MDA levels 30, 60, 90 and 120 minutes after HD session were found to be significantly higher than that of the before and just after the HD sessions' (p < 0,05). EDEF in 90 and 120 minutes after HD session was improved and no correlation between MDA and EDEF was observed. When groups were compared with each other, plasma MDA levels in session with 100 mg iron at the beginning, at the end and 30 minutes after HD were significantly lower than that of the without iron group (p < 0.05). Similarly MDA levels in session with 100 mg iron at the beginning, at the end, 30 minutes and 120 minutes after HD were significantly lower than that of the 20 mg iron (p < 0.05). When EDEF values in sessions with 20 mg iron and without iron were considered, only values 60 and 90 minutes after dialysis were significantly improved in 20 mg iron group. The others were statistically similar.. In the present study, it was observed that I.V administered iron in 20 and 100 mg doses did not cause additional deteriorating effect on oxidant stress and EDEF was even improved by I.V iron.

Topics: Adult; Dose-Response Relationship, Drug; Erythrocyte Deformability; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Oxidative Stress; Renal Dialysis; Sucrose; Time Factors

Iron is essential for the formation of hemoglobin. During long-term treatment with human recombinant erythropoietin (rhEPO), the majority of end-stage renal disease (ESRD) patients will not respond adequately to rhEPO unless substituted with intravenous iron. However, concern exists about possible detrimental effects of parenteral iron on cellular host defense and iron-mediated increments of oxidative stress.. We analyzed phagocytic functions of polymorphonuclear leukocytes (PMN) isolated from 20 ESRD patients on peritoneal dialysis in response to 300 mg of iron sucrose or placebo administered intravenously over two hours in a randomized, double-blind manner. We evaluated Fc gamma R-dependent phagocytosis and killing (primary outcome variable) of opsonized Escherichia coli, Fc gamma R-dependent oxidative burst capacity, and complement receptor 3 (CR3, Mac1, CD11b/CD18)/tumor necrosis factor alpha (TNFalpha)-mediated release of bactericidal lactoferrin before, during, one hour, and two days after administration.. The absolute count and the percentage of E. coli killed by PMN of iron sucrose-treated peritoneal dialysis patients decreased significantly over time in comparison to placebo-treated patients (F = 3.48, df = 4, P = 0.008; F = 3.99, df = 4, P = 0.006, respectively). All secondary outcome variables were not different between both groups over time.. Killing capacity of PMN isolated from ESRD patients decreases in response to high-dose parenteral iron sucrose, possibly in part explaining reported higher hospitalization rates and lower survival rates of dialysis patients receiving frequent and high-dose parenteral iron.

Topics: Anemia; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Neutrophils; Peritoneal Dialysis; Phagocytosis; Prospective Studies; Respiratory Burst

Provision of adequate iron to support erythropoiesis in patients with chronic kidney disease (CKD) is time consuming and may present adherence problems for patients in the outpatient setting. We studied an accelerated regimen of high-dose intravenous iron sucrose therapy in a cohort of iron-deficient, anemic CKD patients.. Intravenous iron sucrose 500 mg was infused over three hours on two consecutive days in 107 CKD patients (glomerular filtration rate, 32.3 +/- 19.6 mL/min/1.73m2, baseline hemoglobin 10.2 +/- 1.7 g/dL). Iron indices (transferrin saturation, ferritin) were measured at baseline and at two and seven days after completion of the iron regimen. Blood pressures were monitored immediately prior to, and hourly throughout the iron sucrose infusions.. Transferrin saturation and serum ferritin increased from 18.5 +/- 8.5% and 177 +/- 123.8 ng/mL at baseline to 40.2 +/- 22.3% and 811 +/- 294.1 ng/mL in 102 evaluated patients (P < 0.015). In 55 patients with additional measurements at 7 days post-dosing, the transferrin saturation and ferritin had fallen to 26.3 +/- 10.6% and 691 +/- 261.8 ng/mL (P < 0.015 compared to two days' post-dose). Blood pressure rose slightly, but not significantly, throughout the infusions, and altering the infusion rate was not necessary. Two patients had seven adverse events that were considered related to iron sucrose.. An accelerated regimen of high-dose intravenous iron sucrose therapy in CKD patients is safe and effective in restoring iron stores, and may potentially save time and improve patient adherence.

Topics: Aged; Anemia; Blood Pressure; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Transferrin; Treatment Outcome

Many haemodialysis patients treated with recombinant human erythropoietin (r-HuEPO) receive intravenous iron supplementation on a regular basis. It has been shown previously that this may result in a transient "oversaturation" of transferrin.. Ten stable haemodialysis patients on r-HuEPO treatment received 100 mg iron saccharate in 60 min, and 1 week later 100 mg in 6 min. Conventional iron metabolism parameters and nontransferrin-bond iron, detected with HPLC after addition of nitrilotriacetate and pretreatment with cobalt, were measured. Also, iron was measured in dialysate.. Serum iron increased from 9.6 +/- 6.2 to 213.7 +/- 49.4 micromol L(-1) (P < 0.001) when iron was given in 60 min, and from 11.1 +/- 4.7 to 219.3 +/- 43.7 micromol L(-1) (P < 0.001) when iron was given in 6 min. Transferrin saturation increased from 0.22 +/- 0.18 to 4.75 +/- 1.35 in protocol 1 and 0.26 +/- 0.16 to 4.91 +/- 1.38 in protocol 2. Nontransferrin-bound iron increased from 0.74 +/- 0.69 to 3.79 +/- 1.41 micromol L(-1) in protocol 1, and from 0.90 +/- 0.92 to 2.90 +/- 0.96 micromol L(-1) in protocol 2. No significant iron concentrations were found in dialysate before or during the iron saccharate infusion.. Nontransferrin-bound iron exists in plasma of dialysis patients after infusion of iron saccharate. There was no difference when 100 mg iron was given in 60 min or in 6 min. Before iron infusion, appreciable concentrations of nontransferrin-bound iron could already be detected. The clinical significance is not clear, but the findings may be important since nontransferrin-bound iron can act as a catalytic agent in the formation of hydroxyl radicals, thus potentially inducing cell damage and atherosclerosis.

Topics: Anemia; Dialysis Solutions; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Protein Binding; Renal Dialysis; Transferrin

We conducted a prospective study to determine the effect of intravenous low-dose iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin (rHuEPO). Sixteen hemodialysis patients (8 males and 8 females; mean age 63.1+/-9.8 years) on maintenance rHuEPO therapy were included in the study. Patients with <100 ng/ml of ferritin received 50 mg iron during every hemodialysis session. Patients with 100-200 ng/ml of ferritin were given 50 mg iron fortnightly. Iron was not supplemented in patients with ferritin levels >200 ng/ml. Mean hematocrit, serum iron levels and transferrin saturations were significantly higher at 6 and 12 months. There was a significant reduction in weekly rHuEPO doses between the start and the 6th and 12th months. Our study shows intravenous iron administration of 100 mg/month may be sufficient to achieve a satisfactory iron status in dialysis patients on maintenance rHuEPO therapy.

Topics: Aged; Anemia; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

Topics: Aged; Anemia, Iron-Deficiency; Epoetin Alfa; Erythrocyte Indices; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hemoglobins; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Middle Aged; Prospective Studies; Recombinant Proteins; Renal Dialysis

It is now more and more evident that anemia of predialysis chronic renal failure (CRF) should be actively treated, since long-standing anemia may cause irremediable damage to the heart. The most common form of treatment of this anemia is subcutaneous erythropoietin (EPO). iron (Fe) deficiency can also contribute to anemia in predialysis CRF, and intravenous iron (i.v. Fe) can frequently improve it. It is possible, therefore, that the combination of EPO and i.v. Fe may have an additive effect, and cause a rapid improvement in anemia with relatively small doses of EPO.. The purpose of this study was an initial study: to assess the ability of a combination of low-dose EPO and i.v. Fe, given weekly for 5 doses, to correct the anemia of predialysis CRF patients compared to the use of i.v. Fe alone in a randomized study. In the follow-up study: to assess the ability of the maintenance of adequate iron stores for one year to achieve and maintain the target Hct of 35% with the minimum dose of EPO. Initial study:. Ninety predialysis CRF patients (creatinine clearance 10-40 ml/min/1.73 m2 received either: Group A (45 patients): 200 mg i.v. Fe as Fe sucrose (Venofer, Vifor Int.) once per week for 5 doses in combination with 2,000 international units (IU) EPO (Eprex, Cilag-Janssen), subcutaneously given simultaneously also for 5 doses. Group B (45 patients): the same dose of i.v. Fe as in Group A but without EPO.. The mean increase in hematocrit (Hct) and hemoglobin (Hb) by one week after the last dose was greater in group A, 4.54 +/- 2.64% (p < 0.01) and 1.37 +/- 0.84 g% (p < 0.01), respectively, than in Group B, 2.74 +/- 2.72% (p < 0.05) and 0.91 +/- 0.78 g% (p < 0.05), respectively. 80% of those in Group A had an increase in Hct of 3 vol% or more compared to 48.9% in Group B (p < 0.01). 40% of those in Group A reached the target Hct of 35% compared to 28.9% in Group B (p > 0.05). Follow-up study: During a 12-month follow-up period, enough i.v. iron was given to maintain the Hct at 35%, while keeping the serum ferritin at < 400 ug/l and % Fe Sat at < 40%. If the i.v. Fe alone was not capable of maintaining the target Hct, EPO was given in increasing doses. Eighteen patients required dialysis. Of the 72 patients who did not require dialysis, 24 (33.3%) maintained the target Hct with i.v. Fe alone, without EPO. All the remaining 48 patients (66.7%) continued to receive EPO in addition to the i.v. Fe, and 47 achieved and maintained the target Hct with a mean EPO dose of 2,979 +/- 1,326 IU/week.. The combination of low-dose EPO and i.v. Fe had a rapid and additive effect on the correction of anemia in CRF predialysis patients. Maintaining adequate iron stores with i.v. Fe during a subsequent maintenance phase allowed the target Hct of 35% to be reached and maintained with low-dose EPO in two-thirds of the predialysis patients and with no EPO at all in one-third.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematocrit; Humans; Infusions, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Sucrose

I.v. iron is commonly administered to haemodialysis patients suffering from anaemia to improve their response to erythropoietin therapy. It has been unclear whether routinely used doses of i.v. iron preparations could result in iron release into plasma in amounts exceeding the iron binding capacity of transferrin. Here, we have studied the effect of 100 mg of iron saccharate given as an i.v. injection on transferrin saturation and the appearance of potentially harmful catalytically active iron.. We followed serum iron, transferrin and transferrin-saturation before and 5-210 min after administration of iron saccharate in 12 patients on chronic haemodialysis due to end-stage renal disease. We measured catalytically active iron by the bleomycin-detectable iron (BDI) assay and transferrin iron forms by urea gel electrophoresis, and studied iron-dependent growth of Staphylococcus epidermidis inoculated into the serum samples in vitro.. The iron saccharate injection resulted in full transferrin saturation and appearance of BDI in the serum in seven out of the 12 patients. BDI appeared more often in patients with a low serum transferrin concentration, but it was not possible to identify patients at risk based on serum transferrin or ferritin level before i.v. iron. The average transferrin saturation and BDI level increased until the end of the follow-up time of 3.5 h. The appearance of BDI resulted in loss of the ability of patient serum to resist the growth of S. epidermidis, which was restored by adding iron-free apotransferrin to the serum. Iron saccharate, added to serum in vitro, released only little iron and promoted only slow bacterial growth, but caused falsely high transferrin saturation by one routinely used serum iron assay.. The results indicate that 100 mg of iron saccharate often leads to transferrin oversaturation and the presence of catalytically active iron within 3.5 h after i.v. injection. As catalytically active iron is potentially toxic and may promote bacterial growth, it may be recommendable to use dosage regimens for i.v. iron that would not cause transferrin oversaturation.

Topics: Adult; Aged; Bleomycin; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Staphylococcus epidermidis; Transferrin

The aim of this prospective study was to test a new protocol for iron supplementation in haemodialysis patients, as well as to assess the utility of different iron metabolism markers in common use and their 'target' values for the correction of iron deficiency.. Thirty-three of 56 chronic haemodialysis patients were selected for long-term (6 months) i.v. iron therapy at 20 mg three times per week post-dialysis based on the presence of at least one of the following iron metabolism markers: percentage of transferrin saturation (%TSAT) <20%; percentage of hypochromic erythrocytes (%HypoE) > 10% and serum ferritin (SF) <400 microg/l. Reasons for patient exclusion were active inflammatory or infectious diseases, haematological diseases, psychosis, probable iron overload (SF > or =400 microg/l) and/or acute need of blood transfusion mostly due to haemorrhage and change in renal replacement treatment.. More than half (51.8%) of the patients of our dialysis centre proved to have some degree of iron deficiency in spite of their regular oral iron supplementation. At the start of the study the mean haemoglobin was 10.8 g/dl and increased after the 6 months of iron treatment to 12.8 g/dl (P<0.0001). The use of erythropoietin decreased from 118 units/kg/week to 84 units/kg/week. The criterion for iron supplementation with the best sensitivity/specificity relationship (100/87.9%) was ferritin <400 microg/l. Patients with ferritin < 100 [microg/l and those with ferritin between 100 microg/l and 400 microg/l had the same increase in haemoglobin but other parameters of iron metabolism were different between the two groups.. Routine supplementation of iron in haemodialysis patients should be performed intravenously. Target ferritin values should be considered individually and the best mean haemoglobin values were achieved at 6 months with a mean ferritin of 456 microg/l (variation from to 919 microg/l). The percentage of transferrin saturation, percentage of hypochromic erythrocytes and ferritin <100 microg/l, were not considered useful parameters to monitor routine iron supplementation in haemodialysis patients. No significant adverse reactions to iron therapy were observed.

Topics: Anemia, Iron-Deficiency; Biomarkers; Drug Administration Routes; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Follow-Up Studies; Glucaric Acid; Hemoglobins; Humans; Iron; Iron Deficiencies; Kidney Failure, Chronic; Male; Middle Aged; Nutritional Support; Practice Guidelines as Topic; Prospective Studies; Recombinant Proteins; Renal Dialysis; Sucrose; Transferrin

Some chronic renal failure patients respond poorly to recombinant human erythropoietin (rHuEPO). In continuous ambulatory peritoneal dialysis (CAPD) patients, such a poor response may indicate inadequate dialysis or low body iron stores. To correct iron deficiency, once-a-week intravenous iron supplementation is recommended. However, hemodialysis patients receive iron supplements three times a week. This study was designed to compare the efficacy of iron supplementation between once-weekly and twice-weekly regimens. In both groups, rHuEPO doses were similar. Seventeen CAPD patients were studied. All had hemoglobin levels less than 10 g/dL. Ten patients were given 100 mg intravenous iron once weekly, and 7 were given 50 mg intravenous iron twice weekly until a total iron dose of 600 mg was achieved (stage I). The patients were crossed over to receive another 600 mg iron (stage II). Hematocrit increased significantly in patients receiving twice-a-week iron supplementation (+3.8% and 6%) compared to those receiving once-a-week iron supplementation (+1.3% and 1.4%) during stages I and II. The ferritin levels were not different between the groups. In conclusion, rHuEPO is more effective when administered with intravenous iron.

Topics: Adult; Anemia; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematocrit; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Organization and Administration; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Sucrose; Transferrin

In the present prospective study we examined the long-term effect of intravenous supplementation with ferric saccharate (IV Fe) in the treatment of the anemia of chronic dialysis patients. All patients, 64 on chronic hemodialysis (HD) and 9 on chronic ambulatory peritoneal dialysis (CAPD), were treated intravenously with this preparation in a dose of 100 mg elemental iron twice monthly. There were five groups. Group 1: 41 HD patients who were receiving erythropoietin (EPO) for at least 6 months prior to the addition of IV Fe. In this group, when IV Fe was given over 6 months, the hematocrit (Hct) increased from a mean of 28.7 to 33.7%. Over the next 6 months, the EPO dose was gradually reduced by a mean of 61.1%, but the mean Hct remained unchanged. Group 2: 11 HD patients who started IV EPO simultaneously with the IV Fe. In this group, over 6 months, the mean Hct increased from 28.1 to 34.1. Over the next 6 months, the EPO dose was gradually reduced by 75.7%, but the mean Hct remained unchanged. Group 3: 12 HD patients who received IV Fe alone for 12 months. The mean Hct increased from 30.5 to 37.9%. Group 4: 4 CAPD patients who had been receiving subcutaneous EPO for at least 6 months prior to IV Fe therapy. Over the subsequent 6 months of IV Fe, the mean Hct increased from 28.4 to 33.3%. Group 5: 5 CAPD patients not on EPO who received IV Fe for 6 months. The mean Hct increased from 27.7 to 35.6%. No adverse effects were seen in any patients throughout the study. In conclusion, adequate Fe supplementation may allow the target Hct of about 33% to be reached without, or with only very low doses of EPO. IV Fe as ferric saccharate is a new and safe form of parenteral iron therapy of the anemia of chronic dialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Drug Combinations; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies; Renal Dialysis

The most frequent i.v. iron preparations used for haemodialysis patients are iron dextran, iron gluconate and iron saccharate. Possible side effects include anaphylactic reactions due to preformed antibodies to dextran or vascular reactions due to unbound iron during treatment with iron gluconate or iron saccharate.. Four dosage regimens of i.v. iron saccharate therapy were studied: 10, 20, 40 and 100 mg, which were given over a time period of 1 min after the end of the dialysis session. Iron metabolism parameters (serum iron concentrations, transferrin saturation and serum ferritin levels) were measured at 0, 1, 5, 15 and 30 min after application and immediately prior to the next dialysis session. All 18 regular haemodialysis patients studied received recombinant human erythropoietin (rHuEpo).. Serum iron levels and transferrin saturation increased significantly following i.v. injection of all doses of iron saccharate. Iron 'oversaturation' of transferrin iron binding did not occur in patients with transferrin levels > 180 mg/dl. However, in patients with transferrin levels < 180 mg/dl the injection of 100 mg iron saccharate resulted in a transferrin saturation of 102.6 +/- 39.5% (two patients with transferrin levels of 87 and 92 mg/dl had transferrin saturation of 119.8 and 149.7%, two patients with transferrin levels of 148 and 171 mg/dl had transferrin saturations of 77.9 and 63.1%, respectively). Serum ferritin levels remained unchanged during the post-injection period and increased by the next dialysis session following injection of 100 mg iron saccharate by 165%.. It is concluded that intravenous iron saccharate injection (10-100 mg even within 1 min) does not result in 'oversaturation' of transferrin iron binding if serum transferrin levels are > 180 mg/dl (high-risk patients; transferrin < 100 mg/dl). This may explain, at least in part, the minimal side effects observed during the i.v. application of iron saccharate. Low-dose i.v. iron saccharate (10-40 mg) is recommended for iron supplementation of haemodialysis patients. If injection of 100 mg is necessary, serum transferrin level should exceed 180 mg/dl. There is, however, no need for fast i.v. injection during routine iron supplementation.

Topics: Adult; Aged; Drug Tolerance; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Injections, Intravenous; Iron; Kidney Failure, Chronic; Kinetics; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

Intradialytic hypotension and intradialytic hypertension are associated with morbidity and mortality in hemodialysis (HD). Many factors can contribute to intra-HD blood pressure (BP) changes, such as drugs with vasoactive properties that can destabilize an already tenuous BP. Intravenous iron sucrose is commonly administered to correct iron deficiency; however, its reported associations with altered hemodynamics have not been consistent.. Prospective cohort study.. 950 outpatients receiving maintenance HD.. Iron sucrose administered during HD.. Intradialytic hypotension, intradialytic hypertension, systolic blood pressure parameters.. Unadjusted and adjusted Poisson and linear repeated measures regression models.. The mean age of patients included in the study was 53±22 years, 43% were female, and 38% were Black. Mean pre-HD SBP was 152±26 (SD) mm Hg. At baseline, the patients who received higher doses of iron sucrose tended to have diabetes, have longer HD sessions, and have a higher frequency of erythropoiesis-stimulating agent use, compared with those who did not receive iron sucrose. In adjusted models, higher doses of iron sucrose were associated with an 11% lower rate of intradialytic hypotension (incidence rate ratio [IRR] for iron sucrose≥100mg vs 0 mg, 0.89 [95% CI, 0.85-0.94]). In adjusted analyses, the administration of higher doses of iron sucrose during HD was associated with intradialytic hypertension (IRR for iron sucrose≥100mg vs 0 mg, 1.07 [95% CI, 1.04-1.10]).. Nonavailability of the precise iron sucrose formulation (volume), laboratory data for each HD session, and outpatient medications. Objective measures of volume status, home medications, and symptom data were not recorded in this study.. We observed an independent association of intravenous iron sucrose administration during HD with a lower risk of intradialytic hypotension and higher risk of intradialytic hypertension. Future studies to better understand the mechanisms underlying these associations are warranted.. Intradialytic hypotension and intradialytic hypertension are common among patients on hemodialysis, and they are associated with morbidity and mortality. Although many factors may contribute to these risks, medications administered during hemodialysis play an important role. We studied the significance of the intravenous iron sucrose used to treat iron deficiency and the impact it may have on blood pressure during dialysis. In our study of 950 outpatient hemodialysis patients, we observed that administration of iron sucrose was associated with higher systolic blood pressure (during and after hemodialysis sessions) as well as a lower risk of intradialytic hypotension. We also observed that higher doses of iron sucrose are associated with the development of intradialytic hypertension.

Topics: Adult; Aged; Blood Pressure; Female; Ferric Oxide, Saccharated; Humans; Hypertension; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis

Sucroferric oxyhydroxide (SOH) is an iron-based phosphate binder (PB), and its use has been widely expanded since its initial approval in 2014. Based on the existing data, however, it remains yet unclear whether its long-term administration is followed by iron overload in dialysis patients. The purpose of this observational study was to evaluate the longstanding effects of SOH on the anemia and iron indices in patients on dialysis.. A total of 110 patients from 3 dialysis centers were included in the study; 49 were under chronic treatment with SOH (cohort A), while 61 were either receiving other PB or no treatment for hyperphosphatemia (cohort B). We initially compared the hematologic profile of patients in 2 cohorts (phase I), and subsequently, we evaluated modifications of the above parameters in the SOH treated patients over a period of 6 months (phase II).. There were no statistically significant differences between 2 cohorts in terms of hemoglobin (Hb; 11.4 ± 1.3 vs. 11.6 ± 0.9 g/dL, p = 0.375), ferritin (473 ± 230 vs. 436 ± 235 ng/mL, p = 0.419) and transferrin saturation (TSAT;26.6 ± 13.2 vs. 26.5 ± 10.6%, p = 0.675), serum phosphate concentration (4.57 ± 1.05 vs. 4.3 ± 0.96 mg/dL, p = ns), and intact PTH (286 ± 313 vs. 239 ± 296 pg/mL, p = ns). Marginally, but significantly higher calcium levels were found in cohort A compared to cohort B (9.18 ± 0.58 vs. 8.9 ± 0.51 mg/dL, respectively, p = 0.008). In phase II, no significant changes were observed in hematological parameters after a 6-month treatment with SOH (Hb: from 11.5 ± 1.1 to 11.4 ± 1.3 g/dL, p = 0.4, serum ferritin levels: from 475 ± 264 to 473 ± 230 ng/mL, p = 0.951, TSAT: from 26.5 ± 16.7 to 26.6 ± 13.2%, p = 0.933). There were also no significant changes in the administration of iron supplements or erythropoietin dose during this period.. SOH is an effective PB, and its long-term use is not complicated by iron overload.

Topics: Aged; Aged, 80 and over; Anemia; Biomarkers; Drug Combinations; Female; Ferric Compounds; Ferritins; Humans; Hyperphosphatemia; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Sucrose

Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease-mineral and bone disorder (CKD-MBD) rat model.. To induce stable renal failure, rats were administered a 0.25% adenine diet for 8 weeks. Concomitantly, rats were treated with vehicle, 2.5 g/kg/day PA21, 5.0 g/kg/day PA21 or 3.0 g/kg/day calcium carbonate (CaCO3). Renal function and calcium/phosphorus/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified.. Rats treated with 2.5 or 5.0 g/kg/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8 weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone.. PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis.

Topics: Animals; Disease Models, Animal; Drug Combinations; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Kidney Failure, Chronic; Male; Phosphorus; Rats; Rats, Wistar; Sucrose; Vascular Calcification

The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients.. De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH).. 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day).. In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Topics: Aged; Chelating Agents; Databases, Factual; Drug Combinations; Europe; Female; Ferric Compounds; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Sucrose

Studies have reported conflicting findings on the infection risk posed by intravenous iron supplementation among hemodialysis (HD) patients. We used a novel study design to assess associations between intravenous iron and infectious diseases.. Patients initiating HD between 1998 and 2008 were extracted from Taiwan's National Health Insurance Research Database. Their first infectious disease in the period between 1.5 years after dialysis initiation and 2010 was identified and defined as the index date. Through the case-crossover design, the odds of exposure to intravenous iron within the 1-month period immediately preceding the index date (i.e., the case period) were compared with iron exposure in three different matched control periods for the same enrollee, thus possibly reducing some unmeasured confounders.. A total of 1410 patients who met our enrollment criteria were extracted from incident HD patients. The odds of intravenous iron exposure during the case period versus total control periods exhibited no significant difference (odds ratio: 1.000, 95% confidence interval: 0.75-1.33). In subgroup analyses, this association remained nonsignificant across patients with diabetes mellitus, heart failure, chronic lung disease, venous catheter for HD, and higher iron load.. We found that intravenous iron supplementation did not increase short-term infection risk among HD patients.

Topics: Administration, Intravenous; Adult; Aged; Bacterial Infections; Cohort Studies; Cross-Over Studies; Databases, Factual; Diabetes Mellitus; Epidemiologic Methods; Female; Ferric Compounds; Ferric Oxide, Saccharated; Heart Failure; Hematinics; Humans; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Lung Diseases; Male; Middle Aged; Multimorbidity; National Health Programs; Renal Dialysis; Taiwan; Time Factors; Young Adult

End-stage renal disease (ESRD) patients present high levels of phosphorus and calcium products in serum, which contribute to the development of vascular calcification and cardiovascular disease, and to low iron stores and carnitine deficiency. For these reasons, ESRD patients are generally supplemented with different medicines. Some of the most common treatments include the use of Carnicor, Venofer, and Sevelamer drugs. Carnicor is used as a source of L-carnitine, acting as antioxidant and neuroprotector. Venofer is used to reduce the deficit of iron. Sevelamer is used to treat hyperphosphatemia. To determine the potential harmful genotoxic effects of these drugs, a group of 214 patients included in a hemodialysis program with different intakes of Carnicor, Venofer, and Sevelamer were evaluated. The levels of basal and oxidative DNA damage, as well as chromosomal damage, were measured in all individuals using the comet and the micronucleus assays, respectively. Our results indicate that Carnicor administration was associated with low but significant increases in the frequency of basal DNA damage and micronuclei. Environ. Mol. Mutagen. 59:302-311, 2018. © 2018 Wiley Periodicals, Inc.

Topics: Carnitine; Chelating Agents; Comet Assay; DNA Damage; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Kidney Failure, Chronic; Lymphocytes; Male; Micronucleus Tests; Middle Aged; Neuroprotective Agents; Oxidative Stress; Sevelamer

A database analysis was conducted to assess the effectiveness of sucroferric oxyhydroxide (SO) on lowering serum phosphorus and phosphate binder (PB) pill burden among adult peritoneal dialysis (PD) patients prescribed SO as part of routine care.. Adult PD patients (n = 258) prescribed SO through a renal pharmacy service were analyzed. Baseline was 3 months before SO prescription. SO-treated follow-up was for 6 months or until either a new PB was prescribed, SO was not refilled, PD modality changed, or patient was discharged. In-range serum phosphorus was defined as ≤5.5 mg/dL.. At baseline, mean serum phosphorus was 6.59 mg/dL with 10 prescribed PB pills/day. The proportion of patients achieving in-range serum phosphorus increased by 72% from baseline to month 6. Prescribed PB pills/day decreased by 57% (10 at baseline to 4.3 at SO follow-up, p < 0.0001). The mean length of SO follow-up was 5.1 months; SO follow-up ended for 38, 27, and 50 patients at months 4, 5, and 6, respectively, due to no further PB fills, and for 10, 11, and 4 patients at months 4, 5, and 6, respectively, due to another PB prescribed. In patients with baseline serum phosphorus >5.5 mg/dL who achieved in-range serum phosphorus during SO follow-up for ≥1 quarter, a notable improvement in serum phosphorus (6.54 to 5.10 mg/dL, p < 0.0001) was observed, and there was a 53% reduction in PB pill burden (9.9 to 4.7, p < 0.0001).. Among PD patients prescribed SO as part of routine care, improvements in serum phosphorus control and >50% reduction in PB pills/day were observed.

Topics: Adult; Aged; Drug Combinations; Female; Ferric Compounds; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Phosphorus; Retrospective Studies; Sucrose

Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients.. Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 - 3) and 6 months (SO 4 - 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed.. At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 - 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 - 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%).. Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day.
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Topics: Adult; Aged; Drug Combinations; Female; Ferric Compounds; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Male; Middle Aged; Phosphorus; Renal Dialysis; Retrospective Studies; Sucrose

Topics: Aged, 80 and over; Anemia; Biomarkers; Carnosine; Darbepoetin alfa; Deficiency Diseases; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Organometallic Compounds; Renal Dialysis; Treatment Outcome; Zinc; Zinc Compounds

Intravenous (IV) iron preparations are widely used in the treatment of anemia in patients undergoing hemodialysis (HD). All IV iron preparations carry a risk of causing hypersensitivity reactions. However, the pathophysiological mechanism is poorly understood. We hypothesize that a relevant number of these reactions are mediated by complement activation, resulting in a pseudo-anaphylactic clinical picture known as complement activation-related pseudo allergy (CARPA).. First, the in-vitro complement-activating capacity was determined for 5 commonly used IV iron preparations using functional complement assays for the 3 pathways. Additionally, the preparations were tested in an ex-vivo model using the whole blood of healthy volunteers and HD patients. Lastly, in-vivo complement activation was tested for one preparation in HD patients.. In the in-vitro assays, iron dextran, and ferric carboxymaltose caused complement activation, which was only possible under alternative pathway conditions. Iron sucrose may interact with complement proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron dextran significantly induced complement activation in the blood of healthy volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric carboxymaltose and iron sucrose only caused significant complement activation in the blood of HD patients. No in-vitro or ex-vivo complement activation was found for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose in HD patients did not lead to significant in-vivo complement activation.. This study provides evidence that iron dextran and ferric carboxymaltose have complement-activating capacities in-vitro, and hypersensitivity reactions to these drugs could be CARPA-mediated.

Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Complement Activation; Complement C1q; Complement C3d; Complement Membrane Attack Complex; Disaccharides; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Humans; In Vitro Techniques; Iron Compounds; Iron-Dextran Complex; Kidney Failure, Chronic; Maltose; Mannose-Binding Lectin; Properdin; Renal Dialysis

Controversy exists about any differences in longer-term safety across different intravenous iron formulations routinely used in hemodialysis (HD) patients. We exploited a natural experiment to compare outcomes of patients initiating HD therapy in facilities that predominantly (in ≥90% of their patients) used iron sucrose versus sodium ferric gluconate complex.. Retrospective cohort study of incident HD patients.. Using the US Renal Data System, we hard-matched on geographic region and center characteristics HD facilities predominantly using ferric gluconate with similar ones using iron sucrose. Subsequently, incident HD patients were assigned to their facility iron formulation exposure.. Facility-level use of iron sucrose versus ferric gluconate.. Patients were followed up for mortality from any, cardiovascular, or infectious causes. Medicare-insured patients were followed up for infectious and cardiovascular (stroke or myocardial infarction) hospitalizations and for composite outcomes with the corresponding cause-specific deaths.. HRs.. We matched 2,015 iron sucrose facilities with 2,015 ferric gluconate facilities, in which 51,603 patients (iron sucrose, 24,911; ferric gluconate, 26,692) subsequently initiated HD therapy. All recorded patient characteristics were balanced between groups. Over 49,989 person-years, 10,381 deaths (3,908 cardiovascular and 1,209 infectious) occurred. Adjusted all-cause (HR, 0.98; 95% CI, 0.93-1.03), cardiovascular (HR, 0.96; 95% CI, 0.89-1.03), and infectious mortality (HR, 0.98; 95% CI, 0.86-1.13) did not differ between iron sucrose and ferric gluconate facilities. Among Medicare beneficiaries, no differences between ferric gluconate and iron sucrose facilities were observed in fatal or nonfatal cardiovascular events (HR, 1.01; 95% CI, 0.93-1.09). The composite infectious end point occurred less frequently in iron sucrose versus ferric gluconate facilities (HR, 0.92; 95% CI, 0.88-0.96).. Unobserved selection bias from nonrandom treatment assignment.. Patients initiating HD therapy in facilities almost exclusively using iron sucrose versus ferric gluconate had similar longer-term outcomes. However, there was a small decrease in infectious hospitalizations and deaths in patients dialyzing in facilities predominantly using iron sucrose. This difference may be due to residual confounding, random chance, or a causal effect.

Topics: Administration, Intravenous; Aged; Anemia; Cardiovascular Diseases; Cause of Death; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infections; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Proportional Hazards Models; Renal Dialysis; Retrospective Studies

Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients.

Topics: Aged; Anemia; Darbepoetin alfa; Disease Management; Erythropoiesis; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Models, Statistical; Neural Networks, Computer; Renal Dialysis; Retrospective Studies

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Topics: Animals; Body Weight; Disease Models, Animal; Drug Combinations; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Homeostasis; Kidney Failure, Chronic; Lanthanum; Male; Mortality; Phosphates; Rats, Wistar; Sevelamer; Sucrose; Vascular Calcification

Ferumoxytol was first approved for clinical use in 2009 solely based on data from trial comparisons with oral iron on biochemical anemia efficacy end points. To compare the rates of important patient outcomes (infection, cardiovascular events and death) between facilities predominantly using ferumoxytol versus iron sucrose (IS) or ferric gluconate (FG) in patients with end-stage renal disease (ESRD)-initiating hemodialysis (HD).. Using the United States Renal Data System, we identified all HD facilities that switched (almost) all patients from IS/FG to ferumoxytol (July 2009-December 2011). Each switching facility was matched with three facilities that continued IS/FG use. All incident ESRD patients subsequently initiating HD in these centers were studied and assigned their facility exposure. They were followed for all-cause mortality, cardiovascular hospitalization/death or infectious hospitalization/death. Follow-up ended at kidney transplantation, switch to peritoneal dialysis, transfer to another facility, facility switch to another iron formulation and end of database (31 December 2011). Cox proportional hazards regression was then used to estimate adjusted hazard ratios [HR (95% confidence intervals)].. In July 2009-December 2011, 278 HD centers switched to ferumoxytol; 265 units (95.3%) were matched with 3 units each that continued to use IS/FG. Subsequently, 14 206 patients initiated HD, 3752 (26.4%) in ferumoxytol and 10 454 (73.6%) in IS/FG centers; their characteristics were very similar. During 6433 person-years, 1929 all-cause, 726 cardiovascular and 191 infectious deaths occurred. Patients in ferumoxytol (versus IS/FG) facilities experienced similar all-cause [0.95 (0.85-1.07)], cardiovascular [0.99 (0.83-1.19)] and infectious mortality [0.88 (0.61-1.25)]. Among 5513 Medicare (Parts A + B) beneficiaries, cardiovascular events [myocardial infarction, stroke and cardiovascular death; 1.05 (0.79-1.39)] and infectious events [hospitalization/death; 0.96 (0.85-1.08)] did not differ between the iron exposure groups.. In incident HD patients, ferumoxytol showed similar short- to mid-term safety profiles with regard to cardiovascular, infectious and mortality outcomes compared with the more commonly used intravenous iron formulations IS and FG.

Topics: Administration, Intravenous; Aged; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrosoferric Oxide; Glucaric Acid; Hematinics; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Prognosis; Proportional Hazards Models; Renal Dialysis; Renal Insufficiency, Chronic; Stroke; United States

The aim of this study was to determine the influence of inflammatory markers, predictive values of CRP and target hemoglobin (Hb) in patients on chronic hemodialysis.. Made is a cross-sectional study of inflammatory agents serum levels-CRP, fibrinogen and ferritin before hemodialysis in 114 patients divided into two groups according to the achieved or unachieved target hemoglobin level in the Cantonal Hospital in Zenica.. The 57 patients (test group) did not reached the target hemoglobin in the range from 10-12 g/dl and CRP values were significantly higher compared to the control group (57 patients) who had reached targeted hemoglobin values. Levels of fibrinogen and ferritin were not significantly different between the control and the test group. CRP values are in negative correlation with the Hb concentration, while fibrinogen and ferritin values had a positive correlation. Significant negative correlation was only found in case of CRP, respectively, higher CRP was at lower levels of blood Hb. It was found that the predictive value of CRP is 6.5 mg/L to achieve target Hb level. If the CRP increases by 1 mg/L, possibilities to achieve the target Hb level in dialysis patients is reduced by 7.5%, with a sensitivity of 51% and specificity of 77%. Ferritin was elevated due to iatrogenic iron saturation, because all patients received intravenous iron and was treated with erythropoietin. By identification and analysis of inflammatory agents and duration ofhemodialysis, are explored the primary influence on hematopoiesis, of course, with the primary application of erythropoietin and adjuvant agents. It has been shown that CRP alone has an impact on the target Hb level, depending on the hemodialysis duration.. The research results show how what looks as routine findings may be helpful in the timely detection of threatening complications and their treatment, and provide extended and improved quality of life for patients on hemodialysis.

Topics: Aged; Anemia; Biomarkers; C-Reactive Protein; Case-Control Studies; Cross-Sectional Studies; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Fibrinogen; Glucaric Acid; Hemoglobins; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Renal Dialysis; ROC Curve; Sucrose

With the recent implementation of bundling reimbursement policy, the use of intravenous (IV) iron preparations for the management of anemia in the end-stage renal disease (ESRD) population has dramatically increased. Iron overload increases the risk of infections in individuals with or without kidney disease. IV iron administration in ESRD patients impairs bacteriocidal capacity of polymorphonuclear leukocytes (PMNs) against Escherichia coli. These preparations consist of an elemental iron core and a carbohydrate shell. In addition to the iron core, the carbohydrate shell may affect PMNs. We therefore examined the effect of iron sucrose, a commonly used preparation, on phagocytic capacity of PMNs from a group of normal individuals against Gram-positive (Staphylococcus aureus) and Gram-negative (E. coli) bacteria.. Iron sucrose was added to heparinized blood samples at pharmacologically-relevant concentrations and incubated for 4 and 24 h at 37°C to simulate in vivo condition. Blood samples mixed with equal volume of saline solution served as controls. To isolate the effects of the carbohydrate shell, blood samples were co-treated with the iron chelator, desferrioxamine.. Iron sucrose caused significant PMN apoptosis and dose-dependent suppression of phagocytic function against both Gram-positive and Gram-negative bacteria. These abnormalities were prevented by desferrioxamine which precluded contribution of the carbohydrate shell to the PMN dysfunction.. At pharmacologically-relevant concentrations, iron sucrose promotes apoptosis and inhibits phagocytic activities of PMNs. The deleterious effect of iron sucrose is mediated by its elemental iron core, not its carbohydrate shell, and as such may be shared by other IV iron preparations.

Topics: Adult; Anemia; Apoptosis; Carbohydrates; Escherichia coli; Female; Ferric Compounds; Ferric Oxide, Saccharated; Flow Cytometry; Glucaric Acid; Hematinics; Humans; Kidney Failure, Chronic; Male; Neutrophils; Phagocytosis; Staphylococcus aureus; Time Factors

Erythropoiesis-stimulating agents and adjuvant intravenous iron have been the primary treatment for anemia in chronic kidney disease. Recent clinical and policy-related events have challenged this traditional paradigm, particularly in regard to erythropoiesis-stimulating agents. Less is known about the impact of these events on intravenous iron use.. United States Renal Data System data (2002-2008) on Medicare hemodialysis patients were examined. For each patient, monthly intravenous iron dose, erythropoiesis-stimulating agent dose, and hemoglobin values were determined. Data were summarized by calendar quarter and plotted for the entire sample and by demographic, clinical, and facility-level subgroups. Marginal means for these variables also were computed to account for changes in patient characteristics over time.. Quarterly iron use increased from 64% in 2002 to 76% in 2008. Mean quarterly iron dose increased from 500 mg in 2002 to 650 mg in 2008. Mean monthly erythropoiesis-stimulating agent dose (per quarter) increased from 2002 to 2006 and then declined. Mean hemoglobin values followed a pattern similar to erythropoiesis-stimulating agent dose. The same patterns in iron, erythropoiesis-stimulating agent dose, and hemoglobin were generally observed across demographic, clinical, facility, and geographic subgroups, with some important differences between subgroups, specifically race and dialysis vintage.. Anemia management patterns have changed markedly between 2002 and 2008, with a steady increase in intravenous iron use even after declines in erythropoiesis-stimulating agent dose and hemoglobin. The clinical impacts of these changes need further evaluation.

Topics: Adolescent; Adult; Aged; Anemia; Child; Child, Preschool; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Iron Compounds; Kidney Failure, Chronic; Male; Middle Aged; Practice Patterns, Physicians'; Renal Dialysis; Time Factors; United States

Anemia is a common and important complication of chronic kidney disease. Treatment includes the use of erythropoiesis-stimulating agents (ESAs) and iron supplementation. However, the optimal schedule of iron supplementation remains to be defined. Thirty-one long-term hemodialysis patients were treated for 1 year (period 1) with ESAs and an intermittent pulse regimen consisting of 100 mg of iron sucrose administered after different dialysis sessions depending on serum ferritin and other laboratory values, but no more than once per week. During the next 3 years (period 2), patients were treated with ESAs and need-based, continuous, low-dose iron. Iron doses were determined on the basis of values and changes of serum ferritin and transferrin saturation every fourth week after the longest interdialysis time interval. Iron doses ranged from 10 to 60 mg of iron sucrose and were given 1-3 times per week. If grounded, we gradually reduced or even abolished the iron doses. A significant increase in the hemoglobin concentration and hematocrit during period 2 in comparison with period 1 was observed. The use of ESAs did not change significantly during period 2 in comparison with period 1, while the use of iron was significantly lower in period 2. Significantly lower values were obtained for serum ferritin, saturation of transferrin, serum iron, and total serum iron-binding capacity during period 2. A better response to ESA therapy (increase in hemoglobin and hematocrit) is achieved with need-based, continuous, low-dose iron replacement.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

A regimen of a single high dose iron administration was initially adopted for patients commencing haemodialysis (HD) treatment. Iron stores are established and iron metabolism and erythropoiesis stabilise allowing haematinic parameters to be more confidently assessed for use in anaemia management decisions. High doses of IV iron delay the need for subsequent iron supplementation. A high-dose, low-frequency iron infusion regimen for all HD patients was adopted. The outcomes of administering this dosage regimen are reported as observational retrospective analysis using patient record data in 2009. Patients received three [median; semi-interquartile range (SIQR) 0.5] high-dose iron infusions during the year. The median infusion dose was 1100 mg iron (SIQR 0.0) and the median amount of iron received during the year by each patient was 3200 mg (SIQR 750). The median haemoglobin (Hb) level prior to infusion was 108 g/l and post infusion 114 g/l; ZHb = 2.656, p = 0.008). Ferritin levels increased from a median of 376 μg/l preinfusion to 690 μg/l postinfusion; Zferritin =-4.796, p < 0.001. The median time between infusions was 125 days (approximately four months). The 51 patients (76%) who received three or less infusions within the study period received 2537 mg (mean) of iron. These findings indicate that both Hb and ferritin levels can be adequately managed using a high-dose, low-frequency regimen of IV iron in patients undergoing HD.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Young Adult

Both erythropoiesis-stimulating agents and iron treatments are underutilized in peritoneal dialysis (PD) patients. Studies to evaluate safety profiles of various intravenous iron preparations are limited in PD patients compared to hemodialysis. No study in the literature compared safety of low-molecular-weight iron dextran (LMW-ID) with that of iron sucrose in PD patients. We aimed to compare adverse-effect profiles of LMW-ID and iron sucrose with varying dosing schedules in PD patients with a hope to foster use of parenteral iron solutions in PD patients.. We retrospectively reviewed patient charts and included patients who were administered iron sucrose or LMW-ID parenterally. Sociodemographic characteristics, clinical features, and pertinent laboratory data were collected. Adverse events which were deemed to be related to infusion of parenteral iron were recorded. We double-checked both physician records and nursing documents for observed adverse events.. A total of 167 chronic PD patients were included in the study, and 92 patients were administered LMW-ID, whereas 75 patients were administered iron sucrose. Only one adverse event occurred in a patient who was administered 500 mg iron sucrose in a single infusion.. This study showed the comparable safety of LMW-ID in varying doses over that of iron sucrose in PD patients.

Topics: Adult; Aged; Anemia; Dextrans; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis

Fibroblast growth factor-23 (FGF23) plays a central role in the development of hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D induced by iron therapy for iron-deficiency anemia. The aim of this study was to examine the effect of intravenous saccharated ferric oxide on serum FGF23 levels and mineral metabolism in hemodialysis patients.. This prospective study enrolled 27 hemodialysis patients who had iron-deficiency anemia defined by a hemoglobin concentration < 10.5 g/dl and serum ferritin < 100 ng/ml. Intravenous saccharated ferric oxide at a dose of 40 mg was administered three times weekly over 3 weeks. The dose of active vitamin D and phosphate binders was kept unchanged. Serum FGF23, intact parathyroid hormone (PTH) and other parameters were prospectively monitored for 5 weeks.. Serum FGF23 levels were markedly elevated [3,453 (338-6,383) pg/ml] at baseline. After 3 weeks of intravenous saccharated ferric oxide treatment, serum FGF23 further increased to 4,701 (1,251-14,396) pg/ml, and returned to the baseline values after 2 weeks of observation. There was also a significant decrease in intact PTH but no changes in serum calcium and phosphorus.. Intravenous saccharated ferric oxide induces further increase in elevated FGF23 levels in hemodialysis patients. This increase does not induce hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D in the absence of functioning kidney, but may result in transient PTH suppression - possibly by directly acting on the parathyroid.

Topics: Aged; Female; Ferric Compounds; Ferric Oxide, Saccharated; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Phosphates; Prospective Studies; Renal Dialysis; Vitamin D

Iron supplementation in hemodialysis patients is fundamental to erythropoiesis, but may cause harmful effects. We measured oxidative stress using labile plasma iron (LPI) after parenteral iron replacement in chronic hemodialysis patients. Intravenous iron saccharate (100 mg) was administered in patients undergoing chronic hemodialysis (N = 20). LPI was measured by an oxidant-sensitive fluorescent probe at the beginning of dialysis session (T0), at 10 min (T1), 20 min (T2), and 30 min (T3) after the infusion of iron and at the subsequent session; P < 0.05 was significant. The LPI values were significantly raised according to the time of administration and were transitory: -0.02 +/- 0.20 micromol/L at the beginning of the first session, 0.01 +/- 0.26 micromol/L at T0, 0.03 +/- 0.23 micromol/L at T1, 0.09 +/- 0.28 micromol/L at T2, 0.18 +/- 0.52 micromol/L at T3, and -0.02 +/- 0.16 micromol/L (P = 0.001 to 0.041) at the beginning of the second session. The LPI level in patients without iron supplementation was -0.06 +/- 0.16 micromol/L. Correlations of LPI according to time were T1, T2, and T3 vs. serum iron (P = 0.01, P = 0.007, and P = 0.0025, respectively), and T2 and T3 vs. transferrin saturation (P = 0.001 and P = 0.0003, respectively). LPI generation after intravenous saccharate administration is time-dependent and transitorily detected during hemodialysis. The LPI increment had a positive correlation to iron and transferrin saturation.

Topics: Aged; Aged, 80 and over; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors

Topics: Anemia; Blood Proteins; Case-Control Studies; Clinical Protocols; Drug Monitoring; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Oxidation-Reduction; Prospective Studies; Renal Dialysis

Detection of iron deficiency in patients with end-stage renal disease (ESRD) remains challenging due to the lack of reliable markers. The immature reticulocyte fractions (IRF) RET-Y and RBC-Y may serve as useful novel markers. We investigated the ability of IRF to detect functional iron deficiency in ESRD patients in comparison to Serum ferritin (SF) and Transferrin saturation (TSAT) and the influence of intravenous iron therapy on these markers.. Cross sectional (n=40) and prospective (n=20) studies of hemodialysis patients were performed; 20 patients received intravenous iron (200 mg) monthly and were followed up for 5 months. Iron deficiency was defined as SF < or =200 microg/L and/or TSAT < or =20%. A RBC-Y < or =171 and/or RET-Y < or =168.7 were criteria for iron deficiency. Correlations between traditional and novel markers were examined. Results are given as mean+/-SEM. Paired t-test was used to test for significance.. 27 male and 13 female patients, mean age of 56.7+/-3.02 years were enrolled in the cross-sectional study. TSAT correlated with RBC-Y and RET-Y, r=0.47 and 0.61, respectively. Correlations for SF with RBC-Y and RET-Y were r=0.23 and 0.22, respectively. In the prospective component (11 males and 9 females of mean age 60+/-3.4 years), RET-Y and RBC -Y remained stable during iron therapy. The coefficients of variation were RBC-Y 2.54%, RET-Y 4.23%, TSAT 28.74% and SF 35.34%.. RBC-Y and RET-Y correlated with TSAT and SF allowing detection of functional iron deficiency. These measures were less susceptible to fluctuations than traditional markers.

Topics: Anemia, Iron-Deficiency; Biomarkers; Cross-Sectional Studies; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Reticulocytes; Time Factors; Transferrin; Treatment Outcome

Use of parenteral iron for anemia management in dialysis patients has greatly increased. Exceeding hemoglobin target levels is not without risk, and whether parenteral iron administration contributes to exceeding targets has not been tested. The authors aimed to determine prevalence of parenteral iron administration and its contribution to exceeding hemoglobin target levels.. The authors performed a retrospective observational study of 149,292 hemodialysis patients using Centers for Medicaid & Medicare Services data. All patients were point prevalent on January 1, 2004; survived through June 30, 2004; had Medicare as primary payer; were treated with erythropoiesis stimulating agents (ESAs); and had valid hemoglobin values in April, May, and June, 2004.. Of the cohort, 58% received parenteral iron; use was more likely among men, whites, younger patients, and patients with end-stage renal disease as a result of diabetes. Age > 75 yr, African American and other races, baseline hemoglobin > 12 g/dl, higher ESA dose, and iron use in months 1 to 4 of the study period were independently associated with the risk of exceeding hemoglobin levels of 12, 13, and 14 g/dl. Receiving iron in month 4 of the study period showed the highest probability of exceeding targets (odds ratios 1.49, 1.43, 1.50 for hemoglobin levels 12, 13, 14 g/dl, respectively).. Parenteral iron use is prevalent, and although adequate iron stores are central to ESA response, iron use may contribute to exceeding recommended hemoglobin levels. Only data from a prospective trial can confirm this association.

Topics: Aged; Anemia, Iron-Deficiency; Centers for Medicare and Medicaid Services, U.S.; Drug Therapy, Combination; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Odds Ratio; Practice Guidelines as Topic; Renal Dialysis; Retrospective Studies; Risk Assessment; Time Factors; Treatment Outcome; United States

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.. 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 prospectively. 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.. 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) microg/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 < or = 16%, serum ferritin < or = 100 microg/L, best with transferrin saturation > 25%, serum ferritin > 600 microg/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.. 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.

Topics: Adult; Aged; Anemia; Comorbidity; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Infusions, Intravenous; Iron-Dextran Complex; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Survival Analysis; Transferrin

The prognosis in elderly patients with advanced chronic heart failure (CHF) and cardio-renal anemia syndrome (CRAS) is ominous, and treatment alternatives in this subset of patients are scarce.. To assess the long-term influence of combined therapy with intravenous (IV) iron and erythropoietin (rHuEPO) on hemoglobin (Hb), natriuretic peptides (NT-proBNP), and clinical outcomes in elderly patients with advanced CHF and mild-to-moderate renal dysfunction and anemia (CRAS) who are not candidates for other treatment alternatives, 487 consecutive patients were evaluated. Of them, 65 fulfilling criteria for entering the study were divided into 2 groups and treated in an open-label, nonrandomized fashion: intervention group (27, combined anemia therapy) and control group (38, no treatment for anemia). At baseline, mean age was 74 +/- 8 years, left ventricular ejection fraction was 34.5 +/- 14.1, Hb was 10.9 +/- 0.9 g/dL, creatinine was 1.5 +/- 0.5 mg/dL, NT-proBNP was 4256 +/- 4952 pg/mL, and 100% were in persistent New York Heart Association (NYHA) Class III or IV. At follow-up (15.3 +/- 8.6 months), patients in the intervention group had higher levels of hemoglobin (13.5 +/- 1.5 vs. 11.3 +/- 1.1; P < .0001), lower levels of natural log of NT-proBNP (7.3 +/- 0.8 vs. 8.0 +/- 1.3, P = .016), better NYHA functional class (2.0 +/- 0.6 vs. 3.3 +/- 0.5; P < .001), and lower readmission rate (25.9% vs. 76.3%; P < .001). In the multivariate Cox proportional hazards model, combined therapy was associated with a reduction of the combined end point all-cause mortality or cardiovascular hospitalization (HR 95%CI 0.2 [0.1-0.6]; P < .001).. Long-term combined therapy with IV iron and rHuEPO may increase Hb, reduce NT-proBNP, and improve functional capacity and cardiovascular hospitalization in elderly patients with advanced CHF and CRAS with mild to moderate renal dysfunction.

Topics: Aged; Aged, 80 and over; Anemia; Chronic Disease; Cohort Studies; Drug Evaluation; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Heart Failure; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Neurotransmitter Agents; Pilot Projects; Prospective Studies; Recombinant Proteins; Survival Rate; Syndrome; Time Factors; Treatment Outcome

Serious concerns have been raised with respect to intravenous (i.v.) iron as a potential oxidative stress inducer in chronic kidney disease patients. Oxidative stress has been linked to uremia-related inflammation and endothelial dysfunction. Because i.v. iron promotes oxidative stress and because uremic patients have numerous defects of antioxidant defense unrelated to iron, we hypothesized that i.v. iron administration might increment oxidative stress and consequently endothelial dysfunction. We undertook a pilot study of 8 patients from our peritoneal dialysis (PD) program who were in stable clinical condition. We measured high-sensitivity C-reactive protein (hsCRP), von Willebrand factor antigen (vWFa), and fibrinogen in serum, and several sonographic parameters: left ventricular ejection fraction, left ventricular mass index, carotid intima media thickness, and the presence of carotid plaques. We also used a sonographic methodology to measure endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) in the brachial artery. Three hours after i.v. administration of 200 mg iron sucrose, we repeated the biochemical measurements and the sonographic vasodilation parameter measurements in the brachial artery. None of the biochemical parameters were modified after administration of i.v. iron sucrose [hsCRP: < 0.5 mg/L (range: < 0.5 - 48 mg/L) vs. < 0.5 mg/L (range: < 0.5 - 37 mg/L), p = 0.46; vWFa: 192% +/- 39% vs. 189% +/- 32%; p = 0.40; fibrinogen: 449 +/- 127 mg/dL vs. 445 +/- 128 mg/dL, p = 0.80). Furthermore, i.v. iron stimulus did not affect either EDV (5.8% +/- 2.7% vs. 7.8% +/- 1.9%, p = 0.09) or EIV (15.3% +/- 2.9% vs. 21.4% +/- 2.2%, p = 0.11). Our data do not support an acute impact of i.v. iron in our PD patients with regard to endothelial-related biochemical parameters or sonographic vasodilation of the brachial artery.

Topics: Brachial Artery; Endothelium, Vascular; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Ultrasonography; Vasodilation

Topics: Coronary Vasospasm; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Middle Aged; Myocardial Ischemia

This study was undertaken to assess the safety and tolerability of the use of intravenous (IV) iron sucrose in the therapy of iron-deficiency anemia in elderly, hemodialysis dependent (HDD), chronic kidney disease (CKD) patients.. This was a multicenter, open-label study in a large consecutive sample of 665 HDD-CKD patients (in 11 locations). Patients received IV iron sucrose therapy in treatment and maintenance dosing cycles over 10-week periods. There were 10 doses of 100 mg of iron sucrose in each drug cycle, and participants could receive multiple cycles of either or both regimens. Variables evaluated in the intent-to-treat population included adverse events (AEs), hemoglobin, and iron indices.. Of the 665 patients, 391 patients were under the age of 65 (younger adults) and 274 were 65 years of age or older (elder adults). Iron needs and erythropoietin dosing were similar in both the elder and younger adult patients. The incidence, severity, and nature of AEs and overall mortality were similar in both age groups. There were no drug-related deaths or drug-related serious AEs in either group. There were no hypersensitivity reactions or allergic reactions in either patient population, even among those with a prior history of intolerance to other parenteral-iron products. Comparison of the two age groups also revealed no differences in the efficacy of iron treatment as reflected by hemoglobin, transferring saturation, and ferritin response.. There is no apparent difference in the safety and efficacy of iron sucrose between elder and younger adults in the treatment of iron-deficiency anemia in HDD patients with CKD.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Geriatrics; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Inflammation is a central component of progressive chronic kidney disease (CKD). Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD. Parenteral iron provokes oxidative stress in patients with CKD; however, its potential to provoke an inflammatory response is unknown. In 20 veterans with CKD, 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 (MCP-1) were measured at timed intervals over 24 h. Patients were then randomized to placebo or N-acetyl cysteine (NAC) 600 mg b.i.d. and the experiment was repeated at 1 week. Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits (P < 0.0001 for time effect). Urinary excretion peaked at 30 min and plasma concentration at 15 min. Plasma MCP-1 concentration fell from 164 +/- 17.7 to 135 +/- 17.7 pg/ml with NAC, whereas it remained unchanged from 133 +/- 12.5 to 132 +/- 17.7 pg/ml with placebo (P=0.001 for visit x antioxidant drug interaction). There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2. At the baseline visit, the urinary excretion rate averaged 305 +/- 66 pg/min and at the second visit 245 +/- 67 pg/min (mean difference 60 +/- 28 pg/min, P = 0.030). There was no improvement in urinary MCP-1 excretion with NAC. In conclusion, iron sucrose causes rapid and transient generation and/or release of MCP-1 plasma concentration and increases urinary excretion rate, and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC. These results may have implications for the progression of CKD with parenteral iron.

Topics: Aged; Chemokine CCL2; Chronic Disease; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Inflammation; Kidney Diseases; Kidney Failure, Chronic; Reproducibility of Results

Topics: Administration, Oral; Dose-Response Relationship, Drug; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Humans; Hypotension; Injections, Intravenous; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome

In vitro evidence suggests that different intravenous iron (i.v. Fe) preparations may be associated with different infection rates. This observational study was to determine if different bacteremia rates are associated with different types or amounts of i.v. Fe preparations.. This retrospective, single-center study was carried out from April 2001 November 2002, a period in which a global switch from ferric gluconate (FG) to iron sucrose (IS) occurred. During Period I (April 2001 - January 2002) FG was the only i.v. Fe administered in our hemodialysis unit. During Period II (February 2002 - November 2002) IS was the only i.v. Fe administered in our unit. Group A (n = 63) received hemodialysis during both Period I and Period II. Group B (n = 41) received hemodialysis either during Period I or Period II.. More bacteremic episodes occurred while IS than while FG was being administered. The adjusted bacteremia incidence rate ratios (IRRs) associated with use of IS vs. FG were 2.92 (95% CI, 1.01 - 8.5) and 2.84 (95% CI 1.32 - 6.09) in Groups A and B, respectively. The adjusted bacteremia IRRs associated with receiving > 2,000 mg of i.v. Fe were 2.42 (95% CI 1.03 - 5.6) and 1.54 (95% CI 0.43 - 5.69) in Groups A and B, respectively. Use of catheters as hemodialysis access increased bacteremia risk in both groups.. Use of iron sucrose is associated with higher bacteremia rates than ferric gluconate. The potential association between the cumulative amount of i.v. Fe administered and bacteremia risk is unclear. Randomized clinical trials are needed to verify our findings.

Topics: Aged; Anemia, Iron-Deficiency; Bacteremia; Chi-Square Distribution; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Poisson Distribution; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Statistics, Nonparametric

Topics: Anemia; Antioxidants; Ascorbic Acid; Drug Therapy, Combination; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Renal Dialysis

Two new intravenous (IV) iron products, ferric gluconate and iron sucrose, recently were approved for use in the United States. We report trends in IV iron use in both incident (1994 to 2001) and prevalent (1994 to 2002) Medicare US dialysis patients.. Included patients had Medicare as a primary payer. Recombinant human erythropoietin doses, IV iron use, and hemoglobin data were obtained from Medicare outpatient files. The most recent cohorts included 241,770 prevalent hemodialysis (HD) patients in 2002 and 11,744 incident HD patients in 2001.. For incident HD patients in the first 9 months of dialysis therapy, the percentage of patients administered IV iron increased sharply between 1994 and 1997 and then increased gradually between 1997 and 2001. In 2002, a total of 84.4% of HD and 19.3% of peritoneal dialysis (PD) patients were administered IV iron. Ferric gluconate use increased slowly in 2000, increased from 5.7% to 18.6% from December 2000 to January 2001, increased to 29.8% in April 2002, and was 23.3% in December 2002. Iron sucrose use increased to 26% by December 2002. The absolute monthly percentage of HD patients administered IV iron dextran decreased from 49.6% in January 2000 to 3.6% in December 2002.. In US patients with end-stage renal disease, IV iron use has increased, although slowly, from 1997 to 2002. Ferric gluconate and iron sucrose have become the predominant form of therapy. IV iron therapy was used in a much smaller percentage of PD compared with HD patients, and racial and geographic variability was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Child; Child, Preschool; Drug Utilization; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Incidence; Infant; Infusions, Intravenous; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Outpatients; Peritoneal Dialysis; Prevalence; Recombinant Proteins; Renal Dialysis; Retrospective Studies; United States

To investigate the effects of intravenous (i.v.) iron replacement on hepatic functions of hepatitis C virus (HCV)-positive haemodialysis patients.. The present retrospective study included 89 HCV-positive and 57 HCV-negative haemodialysis patients. Alanine aminotransferase (ALT) levels were accepted as sustained high if the last three values were >/=20 U/L. All patients and the HCV-positive group were dichotomised into subgroups by the median for dialysis duration, the amounts of i.v. iron administered per year and totally.. Sustained high levels of ALT were significantly more frequent in the HCV-positive group (P < 0.001). In HCV-positive patients, the subgroup with ALT levels >/=20 U/L had significantly higher serum iron levels and mean amounts of i.v. iron administered per year and totally (P < 0.001) and the subgroup with the high mean total amount of i.v. iron had significantly higher serum ALT and iron levels (P < 0.001). Significant positive correlations were found in HCV-positive patients between ALT and serum iron levels (P < 0.001), as well as between ALT both with the mean amounts of i.v. iron administered per year (P = 0006) and totally (P = 0.015). Regression analysis showed that the main parameters effecting ALT were the serum iron level (P < 0.0001) and the mean amount of parenteral iron administered per year (P = 0.032).. We conclude that parenteral iron replacement might contribute to hepatocellular injury in HCV-positive haemodialysis patients.

Topics: Adolescent; Adult; Aged; Alanine Transaminase; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hepatic Insufficiency; Hepatitis C, Chronic; Humans; Injections, Intravenous; Kidney Failure, Chronic; Liver; Male; Middle Aged; Renal Dialysis; Retrospective Studies

To define the adverse events following two different rates and methods of intravenous iron sucrose infusions in children with anaemia due to chronic renal impairment.. Two prospective observational studies were undertaken to characterize the adverse events following iron sucrose administration in children with renal impairment and on erythropoietin. Between January 1999 and April 2003, 5 mg/kg of intravenous (IV) iron sucrose was given over 90 min and repeated 24 h later. Between May 2003 and September 2004, in children with better venous access, a single dose of 2 mg/kg of IV iron sucrose was administered over 3 min during an outpatient clinic visit and haemodialysis sessions. Following infusions, children were monitored for immediate and delayed adverse events. All such events were documented and dealt with appropriately. Test doses were not used.. A total of 870 infusions over 90 min were administered to 72 children. Three children developed abdominal pain. One child developed worsening of hypertension (not related to iron sucrose). Sixty-five doses were administered over 3 min to 20 children, and six minor adverse events were documented.. Although 90 min infusion is associated with fewer adverse events, no life-threatening events were documented in either method.

Topics: Anemia; Child; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Prospective Studies; Recombinant Proteins

Topics: Aged; Anemia; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Heart Failure; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Nandrolone; Nandrolone Decanoate; Sucrose

Elevated cardiac troponin T (cTnT) has been associated with shorter survival in hemodialysis patients. Moreover, intravenous (IV) iron treatment has been held responsible for oxidative stress and accelerated atherosclerosis in these patients. In the present study, we investigated the relationship between cTnT concentration, IV iron treatment, and parameters of iron status. In addition, parameters of oxidative stress, inflammation, and atherosclerosis were evaluated. Predialysis blood samples of 78 chronic hemodialysis patients were analyzed for cTnT, malondialdehyde, creatine kinase (CK), and CK-isoenzyme MB (CK-MB). In addition, the mean value of predialysis serum samples collected during the last year, were considered for homocysteine, ferritin, iron, iron binding capacity, blood cell counts, blood urea nitrogen, creatinine, albumin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), calcium, phosphate, iPTH, cholesterol, and triglyceride. The quantity of IV iron sucrose administered during the last two years was counted from the patients' files. Echocardiography, all events related to ischemic heart disease, and urine volume were also recorded. Elevated cTnT levels (> or =0.10 ng/mL) were found in 18 patients (23.1%). The amount of iron administered was 2264+/-1871 mg with a range 0-7000 mg. Patients with elevated cTnT levels received more IV iron than those with normal cTnT (3692+/-1771 vs. 1761+/-1595 mg, p<0.001). The serum ferritin level was higher in patients with elevated cTnT (median levels; 477 vs. 288 ng/mL; P<0.05). Patients with elevated cTnT were longer on dialysis compared to those with normal levels (median times; 35.5 vs. 15 months, P<0.01) and regression analysis identified the amount of administered iron as an independent factor for elevated cTnT (P<0.01). Intravenous iron treatment and high ferritin concentration are related to high cTnT level, which has previously been incriminated as a survival marker in hemodialysis patients.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Biomarkers; Blood Chemical Analysis; Case-Control Studies; Chi-Square Distribution; Combined Modality Therapy; Coronary Artery Disease; Disease Progression; Dose-Response Relationship, Drug; Female; Ferric Compounds; Ferric Oxide, Saccharated; Follow-Up Studies; Glucaric Acid; Humans; Incidence; Infusions, Intravenous; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Prospective Studies; Reference Values; Renal Dialysis; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Troponin T

The effect of intravenous ascorbic acid was compared with that of intravenous iron in the treatment of functional iron deficiency, as defined as serum ferritin levels over 300 ng/ml and serum iron levels below 50 microg/dl, in patients on chronic hemodialysis. Thirteen patients on chronic hemodialysis with functional iron deficiency received intravenous injections of ascorbic acid, 100 mg, three times a week, after hemodialysis. The therapy was continued until serum ferritin decreased to below 300 ng/ml (3 months at the maximum). The iron and control group were composed of patients who had serum iron levels below 50 microg/dl within 3 months after serum ferritin rose to over 300 ng/ml. Seven patients with the iron group received more than a total of 10 intravenous injections of saccharated ferric oxide (40 mg/dose) after hemodialysis, and seven patients with the control group received no iron preparation during the 3 months. In the ascorbic acid group, while hemoglobin did not change from 10.9 +/- 0.5 g/dl (mean +/- SE) during the three-month period, serum iron increased significantly from 37 +/- 4 microg/dl to 49 +/- 4 microg/dl after one month (p<0.01), and remained elevated until the end of the three-month period. Serum ferritin decreased significantly from 607 +/- 118 ng/ml to 354 +/- 30 ng/ml after 3 months (p<0.01). In the iron group, hemoglobin and serum iron increased significantly from the respective pre-treatment levels during the 2-month period, and serum ferritin rose significantly after 3 months. In the control group, hemoglobin, serum iron and ferritin levels decreased significantly from the respective pre-treatment levels during the 3 months. The recombinant erythropoietin dose remained stable for three months in the ascorbic acid, iron, and control groups, respectively. These results suggest that in hemodialysis patients with a functional iron deficiency, treatment with intravenous ascorbic acid can prevent iron overload due to treatment with intravenous iron, and provide a useful adjuvant means of maintaining hemoglobin and serum iron levels.

Topics: Aged; Anemia, Iron-Deficiency; Ascorbic Acid; Biomarkers; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Treatment Outcome

Topics: Aged; Aged, 80 and over; Anemia; Cost-Benefit Analysis; Drug Costs; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Spain; Sucrose

Identical National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) hematologic and iron targets apply to chronic kidney disease (CKD), peritoneal dialysis (PD), and hemodialysis (HD) patients, yet intravenous (i.v.) nondextran iron therapy is FDA approved only in HD patients. This is because oral iron has been considered adequate in CKD and PD patients, and delivering a parenteral therapy on a frequent basis to an outpatient population with notoriously poor vascular access presents logistical complexities. However, recognition of the need for more aggressive treatment of anemia in the CKD and PD population is growing. This awareness, along with the improved safety profiles of the new, nondextran irons, is tipping the risk-benefit ratio toward more widespread use of i.v. iron in these patients. This article provides a summary of the literature and of our own experience using i.v. iron therapy in CKD and PD patients. Our protocol relies on early monitoring and intervention with i.v. ferric gluconate before severe iron deficiency develops. The proactive approach allows for relatively infrequent treatments at only moderately "high" doses (250 mg) of ferric gluconate. The convergence of convenience and safety may expedite more energetic anemia prevention and treatment in PD and CKD patients.

Topics: Anemia, Iron-Deficiency; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Hematinics; Humans; Infusions, Intravenous; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Peritoneal Dialysis

Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are increasing steadily in the community. We propose that there is a vicious circle established whereby CHF and CRF both cause anemia and the anemia then worsens both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal Anemia (CRA) syndrome. By the combination of active treatment of the CHF and control of the anemia with subcutaneous erythropoietin and intravenous iron, the progression of both the CHF and the CRF can be slowed or stopped in most cases, the quality of life improved and the need for recurrent hospitalization reduced. This will involve cooperation between internists, cardiologists, and nephrologists to allow early and maximal therapy of both the CHF and the anemia.

Topics: Aged; Anemia; Disease Progression; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Heart Failure; Hospitalization; Humans; Injections, Intravenous; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Oxygen Consumption; Recombinant Proteins; Stroke Volume

Multiple parenteral iron (Fe) formulations exist for administration to patients with end-stage renal disease. Although there are concerns regarding their potential toxicities, no direct in vitro comparisons of these agents exist. Thus, the present study contrasted pro-oxidant and cytotoxic potentials of four available Fe preparations: Fe dextran (Fe dext), Fe sucrose (Fe sucr), Fe gluconate (Fe gluc), and Fe oligosaccharide (Fe OS).. Differing dosages (0.06 to 1 mg/mL) of each compound were added to either (1) isolated mouse proximal tubule segments, (2) renal cortical homogenates, or (3) cultured human proximal tubule (HK-2) cells (0.5- to 72-hour incubations). Oxidant injury (malondialdehyde generation) and lethal cell injury (percentage of lactate dehydrogenase release; tetrazolium dye uptake) were assessed. Effects of selected antioxidants (glutathione [GSH], catalase, dimethylthiourea (DMTU), and sodium benzoate also were assessed.. Each test agent induced massive and similar degrees of lipid peroxidation. Nevertheless, marked differences in cell death resulted (Fe sucr >> Fe gluc > Fe dext approximately Fe OS). This relative toxicity profile also was observed in cultured aortic endothelial cells. Catalase, DMTU, and sodium benzoate conferred no protection. However, GSH and its constituent amino acid glycine blocked Fe sucr-mediated cell death. The latter was mediated by mitochondrial blockade, causing free radical generation and a severe adenosine triphosphate depletion state.. (1) parenteral Fes are highly potent pro-oxidants and capable of inducing tubular and endothelial cell death, (2) markedly different toxicity profiles exist among these agents, and (3) GSH can exert protective effects. However, the latter stems from GSH's glycine content, rather than from a direct antioxidant effect.

Topics: Animals; Aorta; Cell Division; Cell Line; Cell Line, Transformed; Cell Survival; Chlorides; Endothelium, Vascular; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Iron; Iron-Dextran Complex; Kidney Failure, Chronic; Kidney Tubules, Proximal; Lipid Peroxidation; Male; Malondialdehyde; Mice; Oligosaccharides; Oxidants; Parenteral Nutrition

The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.

Topics: Aged; Anemia; Disease Progression; Drug Therapy, Combination; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glomerular Filtration Rate; Glucaric Acid; Heart Failure; Humans; Kidney Failure, Chronic; Male; Recombinant Proteins; Stroke Volume; Sucrose

Topics: Anemia, Iron-Deficiency; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Glucaric Acid; Hemoglobins; Humans; Iron; Iron Overload; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Iron deficiency may develop in hemodialysis patients, especially when erythropoietin is given. The role of iron deficiency in the anemia of predialysis chronic renal failure (CRF), however, is much less clear. We have intravenously (IV) administered iron as ferric saccharate in a total dose of 200 mg elemental iron monthly for 5 months to 33 CRF patients who remained anemic despite oral iron supplementation and who had no laboratory signs of iron overload. None was receiving erythropoietin therapy. In 22 of the patients there was an increase in the hematocrit values by the end of the study. These patients were considered responders to intravenous iron (IV Fe) therapy. In 11 patients the iron administration was not associated with improvement of the anemia (nonresponders). Before onset of the IV Fe therapy there were no differences between the responders and nonresponders with regard to degree of anemia, serum ferritin, iron saturation, renal function, or blood pressure. One additional patient was excluded from the study because of a mild reaction during an IV test dose before the study. No worsening of kidney function and no other side effects were noted. In four patients (three responders and one nonresponder) the control of blood pressure necessitated antihypertensive drug therapy adjustment. In conclusion, IV Fe supplementation in two thirds of anemic CRF patients not receiving dialysis resulted in a significant improvement of the anemia, thus avoiding the necessity of erythropoietin or blood administration. This could be achieved by increasing the plasma ferritin levels to 200 to 400 microns/L and/or increasing the iron saturation to 25% to 35%. Intravenous ferric saccharate appears to be a safe and effective method of administering iron for the correction of anemia in CRF patients not receiving dialysis.

Topics: Administration, Oral; Adult; Aged; Anemia; Anemia, Iron-Deficiency; Delayed-Action Preparations; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferrous Compounds; Follow-Up Studies; Glucaric Acid; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Time Factors