Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis

BACKGROUND: Soluble iron salts are toxic for parenteral administration because free iron catalyzes free radical generation. Pyrophosphate strongly complexes iron and enhances iron transport between transferrin, ferritin, and tissues. Hemodialysis patients need iron to replenish ongoing losses. We evaluated the short-term safety and efficacy of infusing soluble ferric pyrophosphate by dialysate. METHODS: Maintenance hemodialysis patients receiving erythropoietin were stabilized on regular doses of intravenous (i.v.) iron dextran after oral iron supplements were discontinued. During the treatment phase, 10 patients received ferric pyrophosphate via hemodialysis as monthly dialysate iron concentrations were progressively increased from 2, 4, 8, to 12 micrograms/dl and were then sustained for two additional months at 12 micrograms/dl (dialysate iron group); 11 control patients were continued on i.v. iron dextran (i.v. iron group). RESULTS: Hemoglobin, serum iron parameters, and the erythropoietin dose did not change significantly from month 0 to month 6, both within and between the two groups. The weekly dose of i.v. iron (mean +/- SD) needed to maintain iron balance during month 6 was 56 +/- 37 mg in the i.v. iron group compared with 10 +/- 23 mg in the dialysate iron group (P = 0.001). Intravenous iron was required by all 11 patients in the i.v. iron group compared with only 2 of the 10 patients receiving 12 micrograms/dl dialysate iron. The incidence of adverse effects was similar in both groups. CONCLUSIONS: Slow infusion of soluble iron pyrophosphate by hemodialysis may be a safe and effective alternative to the i.v. administration of colloidal iron dextran in maintenance hemodialysis patients.     

Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial.

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.     

Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.     

A trial of two iron-dextran infusion regimens in chronic hemodialysis patients

AIM: To test the ability to elicit a hemoglobin (Hb) response in patients on chronic hemodialysis, we prospectively compared two regimens of iron dextran administration, 100 mg once weekly (QW) or 100 mg once every dialysis (QD), both given for 10 doses. PATIENTS AND METHODS: Twenty-three consecutive patients on chronic hemodialysis received iron dextran intravenously if they had absolute or functional iron deficiency. There was no difference in the Hb response between regimens. RESULTS: Both groups had a significant increase in Hb from 10.5+/-1.5 g/dl at baseline, to 11.1+/-1.7 g/dl at 1 month, 1.4+/-2.1 g/dl at 2 months and 11.6+/-1.9 g/dl at 3 months. The increment in Hb at 1 month was similar (QD 0.62+/-1.245 g/dl vs. QW 0.64+/-1.464 g/dl) between the two groups despite a large difference in the amount of iron received. Serum ferritin, transferrin saturations or epoetin dose did not change significantly. At the end of 3 months 12 patients did not need further iron therapy as judged by the serological markers of iron stores. Of these 12 patients, 3 had serum ferritins of > 1,000 ng/ml. Weekly dosing of iron was associated with more medication errors than dosing every dialysis. Baseline iron stores could not predict the responsiveness to intravenous iron therapy as judged by an increase in Hb concentration at 1 month or at 3 months. CONCLUSION: This study confirms the efficacy of 1,000 mg of intravenous iron administered over a 3-month period in patients with functional iron deficiency. It underscores the importance of careful monitoring of iron stores and highlights the need for developing better parameters of functional iron stores in hemodialysis patients.     

Sodium ferric gluconate therapy in renal transplant and renal failure patients

Intravenous infusion of sodium ferric gluconate (Ferrlecit) has been reported to be effective and safe in pediatric and adult hemodialysis patients with iron depletion. We sought to expand on the previous studies by treating 13 consecutive pediatric renal failure and renal transplant patients with sodium ferric gluconate doses that were higher than previously reported. Efficacy was defined as: (1) an increase in hematocrit of ≥3 vol% with no change or a decrease in erythropoietin dose or (2) a stable hematocrit with a decrease of ≥25% in the erythropoietin, 2 weeks to 2 months after sodium ferric gluconate infusion. Two dosing strategies were employed: (1) high dose, where single dose sodium ferric gluconate (mg) ≈ calculated iron deficit, and (2) sodium ferric gluconate, 62.5 mg/dose for children <40 kg, 125 mg/dose for children >40 kg, infused on eight consecutive hemodialysis runs. There was only one self-limited adverse reaction in 60 doses. Three patients with previous adverse reactions to iron dextran tolerated sodium ferric gluconate without adverse effect. Sodium ferric gluconate was efficacious in eight out of ten patients that received a cumulative dose >5 mg/kg. The mean hematocrit increased 30.3±7.8 to 36.4±4.4 vol% (P=0.04) and the mean erythropoietin dose decreased 251.5±149.1 to 100.7±113.0 units/kg/week (P=0.02). Although sodium ferric gluconate appears to be effective and safe at the doses used, multicenter, prospective pharmacokinetic and clinical trials of sodium ferric gluconate should be conducted in children. Received: 29 February 2000 / Revised: 20 June 2000 / Accepted: 27 June 2000     

Update on adverse drug events associated with parenteral iron.

BACKGROUND: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex. METHODS: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars. CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.     

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.     

Continuous intravenous sodium ferric gluconate improves efficacy in the maintenance phase of EPOrHu administration in hemodialysis patients

Although intravenous iron has proved to optimize the efficacy of EPOrHu in hemodialysis patients, hitherto no consensus exists with respect to the best regimen of intravenous iron administration. We started a prospective randomized study in 26 patients undergoing chronic hemodialysis who had adequate iron metabolism indices (serum ferritin >100 microg/l; %TSAT >20%; %HypoE <10% and CHr >26 pg) and were in the maintenance phase of EPOrHu administration (target hemoglobin obtained >10 g/dl). All patients were receiving sodium ferric gluconate (Ferrlecit) intermittently prior to the study and after a 1-month wash-out period where iron was not administered patients were randomized to receive the same previous dose of intravenous iron either in a continuous (6.25-21.3 mg in every hemodialysis session) or an intermittent regimen (62.5 mg every 1-4 weeks, not modifying the previous schedule of administration). At 16 weeks, the continuous group showed a significant increment in serum Hb (11.83 +/- 1.12 g/dl) with respect to baseline (10.96 +/- 1.31 g/dl) (p < 0.05), whereas no differences were obtained in intermittent group (baseline: 11.16 +/- 1.03 g/dl; 16 weeks: 11.14 +/- 0.90 g/dl, NS). In contrast with the intermittent group, serum ferritin increased significantly in the continuous group (16 weeks: 508 +/- 157 microg/l; baseline: 368 +/- 56 microg/l; p < 0.05), whereas %TSAT and CHr did not modified during the study in both groups. %HypoE increased significantly with respect to baseline values in the continuous group (p < 0.05) and close to significantly different in the intermittent group (p = 0.06). Our study suggests that hemodialysis patients in the maintenance phase of EPOrHu administration would obtain further benefit in terms of serum hemoglobin level with a continuous intravenous serum ferric gluconate regimen, at least in the short term.     

On the relative safety of parenteral iron formulations.

BACKGROUND: Intravenous iron is usually required to optimize the correction of anaemia in persons with advanced chronic kidney disease and end-stage renal disease. Randomized clinical trials may have insufficient power to detect differences in the safety profiles of specific formulations. METHODS: We obtained data from the US Food and Drug Administration on reported adverse drug events (ADEs) related to the provision of three formulations of intravenous iron during 1998-2000. We estimated the relative risks [odds ratios (OR)] of ADEs associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran using 2 x 2 tables. RESULTS: The total number of reported parenteral iron-related ADEs was 1981 among approximately 21,060,000 doses administered, yielding a rate of 9.4 x 10(-5), or approximately 94 per million. Total major ADEs were significantly increased among recipients of higher molecular weight iron dextran (OR 5.5, 95% CI 4.9-6.0) and sodium ferric gluconate complex (OR 6.2, 95% CI 5.4-7.2) compared with recipients of lower molecular weight iron dextran. We observed significantly higher rates of life-threatening ADEs, including death, anaphylactoid reaction, cardiac arrest and respiratory depression among users of higher molecular weight compared with lower molecular weight iron dextran. There was insufficient power to detect differences in life-threatening ADEs when comparing lower molecular weight iron dextran with sodium ferric gluconate complex. CONCLUSIONS: Parenteral iron-related ADEs are rare. Using observational data, overall and most specific ADE rates were significantly higher among recipients of higher molecular weight iron dextran and sodium ferric gluconate complex than among recipients of lower molecular weight iron dextran. These data may help to guide clinical practice, as head-to-head clinical trials comparing different formulations of intravenous iron have not been conducted.     

Total dose infusion iron dextran therapy in predialysis chronic renal failure patients

BACKGROUND: Intravenous iron therapy is now the standard modality of iron supplementation in hemodialysis patients, but its role in predialysis chronic renal failure patients is less well established. The efficacy and safety of intravenous iron dextran as a total dose infusion in predialysis chronic renal failure patients, not receiving erythropoietin was assessed in this study. METHODS: Fifty-six predialysis chronic renal failure patients with anemia, not receiving erythropoietin were included in the study, after obtaining informed consent. Hemoglobin, serum creatinine, creatinine clearance rate and serum ferritin were assessed in all the patients at baseline. Iron dextran in a dose of 1 g dissolved in 500 mL normal saline was administered to all patients as a total dose infusion over 6 h after a prior test dose. Patients were kept in hospital under observation for at least 24 h. All the parameters were repeated in all the patients at 12 weeks and in 21 patients at 1 year. RESULTS: The mean hemoglobin (g/dL) in the patients at baseline and at 12 weeks was 8.28 +/- 0.57 and 9.22 +/- 0.44 respectively (p < 0.001). The mean serum ferritin (ng/mL) increased from 29.73 +/- 9.38 at baseline to 218.43 +/- 15.66 at 12 weeks (p < 0.00001). The mean ferritin value in the 21 patients at 1 year was 136.5 +/- 23.4 (p < 0.01). There were no major adverse events and only minor side effects were observed in 4.9% patients. CONCLUSION: Iron dextran as a total dose infusion corrects anemia in predialysis patients and is an effective method to replenish iron stores. The effect on serum ferritin are evident even at 1 year after the total dose infusion.     

Diagnostic value of iron indices in hemodialysis patients receiving epoetin.

BACKGROUND: Iron deficiency remains a common cause of hyporesponsiveness to epoetin in hemodialysis patients. However, considerable controversy exists regarding the best strategies for diagnosis and treatment. METHODS: As part of a multicenter randomized clinical trial of intravenous versus subcutaneous administration of epoetin, we made monthly determinations of serum iron, total iron binding capacity, percentage transferrin saturation, and serum ferritin. If a patient had serum ferritin <100 ng/mL or the combination of serum ferritin <400 ng/mL and a transferrin saturation <20%, he/she received parenteral iron, given as iron dextran 100 mg at ten consecutive dialysis sessions. We analyzed parenteral iron use during the trial, the effect of its administration on iron indices and epoetin dose, and the ability of the iron indices to predict a reduction in epoetin dose in response to parenteral iron administration. RESULTS: Eighty-seven percent of the 208 patients required parenteral iron to maintain adequate iron stores at an average dose of 1516 mg over 41.7 weeks, or 36 mg/week. Only two of 180 patients experienced serious reactions to intravenous iron administration. Two thirds of the patients receiving parenteral iron had a decrease in their epoetin requirement of at least 30 U/kg/week compared with 29% of patients who did not receive iron (P = 0.004). The average dose decrease 12 weeks after initiating iron therapy was 1763 U/week. A serum ferritin <200 ng/mL had the best positive predictive value (76%) for predicting a response to parenteral iron administration, but it still had limited clinical utility. CONCLUSIONS: Iron deficiency commonly develops during epoetin therapy, and parenteral iron administration may result in a clinically significant reduction in epoetin dose. The use of transferrin saturation or serum ferritin as an indicator for parenteral iron administration has limited utility.     

Controversies in iron management

BACKGROUND: Iron therapy is required in hemodialysis patients receiving erythropoietic stimulators in order to achieve the target hemoglobin in the most efficient way. While oral iron has been disappointing in this regard, parenteral iron has been widely used, despite a significant incidence of severe side effects when iron dextran is used. The recent availability of a more effective form of oral iron (heme-iron), and safer forms of parenteral iron (iron sucrose and iron gluconate) has made iron management in this population simpler. Many questions remain, however, about the use, efficacy, and safety of these compounds in hemodialysis patients. METHODS: Current literature was reviewed and combined with the authors' clinical experience to address a number of current questions regarding the use of iron in hemodialysis patients. RESULTS: Although oral non-heme iron is infrequently sufficient to maintain iron stores in hemodialysis patients, recent studies suggest that heme-iron may be more useful in this regard. Heme-iron is absorbed to a greater extent than non-heme iron, and is better tolerated. Small studies have shown that when heme-iron is administered, less parenteral iron and lower doses of erythropoietin (EPO) are needed to maintain target hemoglobin. Current evidence suggests that both iron sucrose and iron gluconate are safer than iron dextran, and the latter should only be used in extraordinary circumstances. While in vitro studies have demonstrated some differences in the effects of iron sucrose and iron gluconate on cellular toxicity, the clinical importance of these has not been determined. Both compounds can be used safely for repletion and maintenance therapy, and doses of up to 300 mg of either are generally well tolerated when such higher doses are needed, as in peritoneal dialysis (PD) patients or chronic kidney disease (CKD) patients not on dialysis. CONCLUSION: A number of questions remain regarding the appropriate use, efficacy, and potential toxicity of iron therapy in dialysis patients. Further prospective research should address the myriad questions raised in this review.     

Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compared to placebo and iron dextran

BACKGROUND: Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control. METHODS: This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC na?ve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline. RESULTS: A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001. CONCLUSION: SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.     

Intravenous iron preparations and ascorbic acid: effects on chelatable and bioavailable iron

BACKGROUND: There is growing interest to use ascorbic acid as adjuvant therapy for patients with recombinant human erythropoietin-hyporesponsiveness (rHuEpo). Several clinical studies showed the beneficial effect of ascorbic acid treatment on hematologic parameters in rHuEpo-treated hemodialysis patients with elevated or even normal iron stores. However, whether ascorbic acid directly affects stability and cellular metabolism of intravenous iron preparations (IVI) is not well understood. METHODS: The preparations for testing were iron sucrose (Venofer), ferric gluconate (Ferrlecit), and iron dextran (INFeD). HepG2-cells were used to investigate effects of ascorbic acid on iron bioavailability for the intracellular labile iron pool (LIP) from IVI by using the fluorescent calcein-assay, and cellular ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). Transferrin-chelatable iron was assessed by fluorescent-apotransferrin, and cell toxicity was assayed by neutral red cytotoxicity test. RESULTS: The effects of vitamin C on different preparations do not reflect their known chemical stability (i.e., iron dextran >iron sucrose >ferric gluconate). Effects of ascorbic acid on the increase of the intracellular LIP, as well as on increasing mobilization to transferrin in serum, were limited to iron sucrose. Ascorbic acid did not increase cell toxicity and the amount of low molecular weight iron in serum. CONCLUSION: We conclude that corrected ascorbic acid levels in hemodialysis (HD) patients could increase the amount of bioavailable iron from iron sucrose, but not from other classes of IVI. Vitamin C administration could therefore result in a lower need of iron sucrose to correct anemia.     

A randomized controlled trial of oral versus intravenous iron in chronic kidney disease

BACKGROUND: It is unknown whether intravenous iron or oral iron repletion alone can correct anemia associated with chronic kidney disease (CKD). We conducted a randomized multicenter controlled trial in adult anemic, iron-deficient non-dialysis CKD (ND-CKD) patients (>or=stage 3) not receiving erythropoiesis-stimulating agents (ESAs). METHODS: The participants were randomized to receive either a sodium ferric gluconate complex (intravenous iron) 250 mg i.v. weekly x 4 or ferrous sulfate (oral iron) 325 mg t.i.d. x 42 days. Hemoglobin (Hgb), ferritin and transferrin saturation (TSAT) were measured serially, and the Kidney Disease Quality of Life (KDQoL) questionnaire was administered on days 1 and 43. The primary outcome variable was change from baseline (CFB) to endpoint in Hgb values. RESULTS: Seventy-five patients were analyzed (intravenous iron n = 36, oral iron n = 39). CFB in Hgb was similar in the two groups (intravenous iron 0.4 g/dl vs. oral iron 0.2 g/dl, p = n.s.). However, the increase in Hgb was only significant with intravenous iron (p < 0.01). In comparison to oral iron, intravenous iron achieved greater improvements in ferritin (232.0 +/- 160.8 vs. 55.9 +/- 236.2 ng/ml, p < 0.001) and TSAT (8.3 +/- 7.5 vs. 2.9 +/- 8.8%, p = 0.007). Intravenous iron caused greater improvements in KDQoL scores than oral iron (p < 0.05). The most common side effect reported with intravenous iron was hypotension, while constipation was more common with oral iron. CONCLUSIONS: Oral and intravenous iron similarly increase Hgb in anemic iron-depleted ND-CKD patients not receiving ESAs. Although in comparison to oral iron, intravenous iron may result in a more rapid repletion of iron stores and greater improvement in quality of life, it exposes the patients to a greater risk of adverse effects and increases inconvenience and cost.     

Low-molecular weight iron dextran and iron sucrose have similar comparative safety profiles in chronic kidney disease

Serious adverse events that occur with the administration of iron dextran are due to the high molecular weight preparations. Conclusions that iron sucrose and ferric gluconate are safer than iron dextran may be premature. Published literature comparing safety profiles of available parenteral iron products is reviewed. Administration of iron salts to pre-dialysis patients with chronic kidney disease may not be optimal. We recommend the total dose infusion of low molecular weight iron dextran as an option for iron replacement.     

Total dose iron infusion: safety and efficacy in predialysis patients

Iron deficiency anemia is not uncommon in predialysis patients. Oral iron often cannot maintain adequate iron stores. Hence we evaluated the safety and efficacy of total dose infusion (TDI) of iron in these patients. Anemic predialysis patients were screened and those with Hb < 7.0 g/dL and serum ferritin < 200 ng/mL were selected. Patients with active bleeding and acute liver disease were excluded. All patients were on oral iron 100 mg/day. None of the patients were on erythropoeitin. 11 patients (6 males and 5 females), aged 45.9 +/- 15 yrs, were suitable. Hb was 5.9 +/- 1.0 g/dL and serum ferritin was 89.5 + 50 ng/mL. The preparation used was iron dextran. A test dose of 25 mg in 100 mL normal saline was administered over 1 hr to all patients. One patient had fever and chills during the test dose and was not given TDI. 10 patients received TDI. None of these patients had any problem during the infusion. The dose of iron administered was 900 + 316.2 mg. One patient who received 1600 mg had arthralgia-myalgia and another patient had thrombophlebitis following TDI. One month after TDI, Hb was 8.0 + 1.0 g/dL and serum ferritin was 362 ng/mL. We feel that TDI is a safe and effective method of correcting iron deficiency in predialysis patients.     

A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.     

Intramuscular iron replenishment and replacement combined with testosterone enanthate in maintenance hemodialysis anemia: a follow-up of up to 8 years on 16 patients

Sixteen chronic uremics who showed exhausted bone marrow iron stores and mean hematocrit values of 20.9 +/- 4.2% at the time of starting maintenance hemodialysis (HD) were treated by means of intramuscular iron dextran (IMD) (400 mg/month) for six months. By the end of this replenishment period, stainable bone marrow iron was observed and mean hematocrit values increased to 27.2 +/- 4.9% (p greater than 0.001). At this time, 200 mg of IMD/month and testosterone enanthate (1.5 g/month) were prescribed for the whole follow-up period (up to 8 years). The observed mean hematocrit values were up to 46.1 +/- 1.6%. Major side effects were not observed. The process of slow iron reabsorption from the intramuscular injection site (up to 4 weeks) also implies the splitting of iron from dextran, therefore preventing bone marrow deposits of iron dextran complexes which make iron unavailable for erythropoiesis. High doses of testosterone enanthate can normalize hematocrit values of maintenance hemodialysis patients with replenished bone marrow iron stores.     

Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study

Few data exist to guide treatment of anemic hemodialysis patients with high ferritin and low transferrin saturation (TSAT). The Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) trial was designed to evaluate the efficacy of intravenous ferric gluconate in such patients. Inclusion criteria were hemoglobin or=225 IU/kg per wk or >or=22,500 IU/wk. Patients with known infections or recent significant blood loss were excluded. Participants (n=134) were randomly assigned to no iron (control) or to ferric gluconate 125 mg intravenously with eight consecutive hemodialysis sessions (intravenous iron). At randomization, epoetin was increased 25% in both groups; further dosage changes were prohibited. At 6 wk, hemoglobin increased significantly more (P=0.028) in the intravenous iron group (1.6 +/- 1.3 g/dl) than in the control group (1.1 +/- 1.4 g/dl). Hemoglobin response occurred faster (P=0.035) and more patients responded after intravenous iron than in the control group (P=0.041). Ferritin 800 ng/ml had no relationship to the magnitude or likelihood of responsiveness to intravenous iron relative to the control group. Similarly, the superiority of intravenous iron compared with no iron was similar whether baseline TSAT was above or below the study median of 19%. Ferritin decreased in control subjects (-174 +/- 225 ng/ml) and increased after intravenous iron (173 +/- 272 ng/ml; P<0.001). Intravenous iron resulted in a greater increase in TSAT than in control subjects (7.5 +/- 7.4 versus 1.8 +/- 5.2%; P<0.001). Reticulocyte hemoglobin content fell only in control subjects, suggesting worsening iron deficiency. Administration of ferric gluconate (125 mg for eight treatments) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT 相似文献