Increase of body iron stores estimated by the increase of serum ferritin concentration during a treatment of 200 mg Fe++ daily after gastrointestinal surgery

A 6-week iron therapy of 200 mg Fe++ daily was given to 13 men and 12 women who had previously undergone various kinds of common gastrointestinal surgery and who had empty iron stores estimated from low serum ferritin concentration. The results were compared with those of a control group corresponding to the study group in respect of sex, number of patients, primary disease, previous operation, empty iron stores (serum ferritin), blood hemoglobin, serum iron, sedimentation rate, blood leukocytes, serum transferrin, folate and vitamin B12. The iron therapy restored the lack of body iron, for the serum ferritin concentrations increased from 12 +/- 7 to 30 +/- 11 micrograms/l (p less than 0.001) in the men and from 10 +/- 6 to 30 +/- 12 micrograms/l (p less than 0.001) in the women, whereas the corresponding changes in the control group were from 10 +/- 9 to 11 +/- 8 micrograms/l and from 11 +/- 8 to 13 +/- 11 micrograms/l in the men and women, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iron status in patients receiving erythropoietin for dialysis-associated anemia

Adequate body iron stores are crucial to assuring rapid and complete response to recombinant human erythropoietin (rHuEPO). In the present study, markers of iron storage were examined in 27 patients with normochromic, normocytic anemia undergoing acute rHuEPO (150 to 300 U/kg t.i.w.) treatment for anemia. We calculated projected iron needed for new hemoglobin synthesis from the difference between initial and target hemoglobin concentrations, initial iron reserves available from initial serum ferritin levels, and net projected surplus or deficit from the difference between needs and reserves. Of 22 patients predicted to develop iron deficiency (mean projected deficit 268 +/- 70 mg), 20 developed evidence of exhausted iron stores (transferrin %sat less than 16 or ferritin less than 30 micrograms/liter) before reaching target hemoglobin; two predicted to become deficient (projected deficit less than 100 mg) did not; and all five predicted to avoid iron deficiency (mean projected surplus 177 +/- 20 mg) remained iron replete. During acute rHuEPO therapy net body iron balance remained neutral in patients receiving no iron supplements and increased 5 mg/kg in patients prescribed oral ferrous sulfate. However, in patients given iron dextran i.v. less than 60% of elemental iron administered became measurable as iron stores or usable for hemoglobin synthesis.     

Comparison of intravenous ascorbic acid versus intravenous iron for functional iron deficiency in hemodialysis patients

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.     

Effect of body iron stores on serum aluminum level in hemodialysis patients.

To evaluate the influence of body iron stores on the serum aluminum (Al) level, we studied the correlation between iron status (the serum ferritin, serum iron and transferrin saturation) and serum Al levels in 68 severely anemic hemodialysis patients. Among them, 36 underwent the desferrioxamine (DFO) mobilization test. These 68 patients were divided into three groups according to their serum ferritin level. The basal Al level in the patient group was 41.4 +/- 37.4 micrograms/l (control, 4.1 +/- 2.4 micrograms/l). The serum Al level after DFO infusion of the patient group was 111.1 +/- 86.8 micrograms/l. A significantly higher basal Al and peak Al level after DFO infusion were found in group 1 patients (serum ferritin less than 300 micrograms/l) when compared to group 2 (serum ferritin 300-1,000 micrograms/l) and group 3 (serum ferritin greater than 1,000 micrograms/l) patients. A significant negative correlation between serum ferritin and basal serum Al (r = -0.544, p = 0.0001), as well as peak serum Al after DFO infusion (r = -0.556, p = 0.0001), was noted. Similarly, a negative relationship between serum Al (both basal and peak) and either serum iron or transferrin saturation was noted. However, there was no correlation between the serum Al level and the dosage of aluminum hydroxide. In conclusion, serum ferritin, serum iron and transferrin saturation were inversely correlated with serum Al in our hemodialysis patients. Iron deficiency may probably increase Al accumulation in these patients.     

Lack of body iron after total gastrectomy for adenocarcinoma of the stomach: a serum ferritin follow-up

The postoperative evaluation over two years of body iron stores by measurement of serum ferritin concentrations in 43 patients who underwent total gastrectomy, for adenocarcinoma of the stomach showed that more than 50% of the patients had depleted iron stores. The iron stores were often already depleted preoperatively and were only slightly reduced postoperatively according to the time since surgery. Total gastrectomy produced an acute and significant increase in subnormal, but not in normal or high, serum ferritin concentrations, for a period of three months. Some, although not all, patients presenting metastasis during follow-up showed an increase in serum ferritin concentrations. This study would indicate that empty iron stores are common in patients with adenocarcinoma of the stomach, that total gastrectomy produces an acute increase in subnormal serum ferritin values, but iron stores are not replaced during follow-up and that high serum ferritin concentrations are rarely seen in patients with adenocarcinoma of the stomach.     

Dietary iron overload in southern African rural blacks

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (rHuEpo). In these patients, iron therapy may be a hazard, leading to iron overload and consequently to hemosiderosis. Recent studies suggest that intravenous ascorbic acid (IVAA) may circumvent rHuEpo resistance. The aim of our study was to show the effects of IVAA on FID and whether this results in a better correction of anemia in HD patients with stable hemoglobin (Hb) concentration and FID. METHODS: Twenty-seven HD patients with serum ferritin >300 microg/l, transferrin saturation (TS) <20% and hemoglobin (Hb) <10 g/dL were selected andrandomly divided into two groups to enter a cross-over trial with IVAA. In group I IV vitamin C 500 mg was administered three times a week for three months and discontinued in the next three months of the study. Vitamin C was not given the first three months in group II (control group, first three months of the study), who then received 500 mg IV three times a week for the next three months. RESULTS: Hb and TS% significantly increased (baselines vs 3 months, Hb 9.2 +/- 0.2 vs 10.0 +/- 0.3 g/dL, TS% 17.5 +/- 0.6 vs 25.7 +/- 1.7, respectively p < 0.01 and p <0.001) in group I after three months; ferritin fell significantly from 572 +/- 40 to 398 +/- 55 microg/L (p<0.004). Ten patients completed the study: mean Hb and TS% fell significantly (3 months vs final, Hb 9.9 +/- 0.3 vs 8.9 +/- 0.2 g/dL, TS% 25.1 +/- 1.2 vs 19.1 +/- 1.1, respectively p < 0.01 and p <0.001), while mean ferritin did not change. Mean Hb, ferritin and TS% remained unchanged in group II after three months. Hb and TS% mean values rose significantly (3 months vs final, Hb 9.0 +/- 0.2 vs 9.9 +/- 0.2 g/dl, TS% 18.4 +/- 1.0 vs 27.0 +/- 1.0, respectively p < 0.005 and p <0.001), and ferritin markedly decreased from 450 +/- 50 to 206 +/- 24 microg/L (p < 0.001) at the end of the study. The rHuEpo dose was kept unchanged throughout the study. Differences were analyzed after three months. Mean Hb rose (0.8 +/- 0.2 g/dL) in group I but dropped (-0.1 +/- 0.1 g/dL) (p< 0.009) in group II. Ferritin dropped in both groups (group I vs group II, -173 + /-48 vs - 33 +/- 21 microg/L) (p < 0.01) while TS% increased (group I vs group II, 8.2 +/- 1.5 vs 0.4 +/- 0.7) (p < 0.001). CONCLUSION: IVAA may partially correct FID and consequently help rHuEpo hyporesponsive anemia.     

Serial ferritin concentrations in hemodialysis patients receiving intravenous iron

BACKGROUND: Treatment of the anemia of chronic renal failure with intravenous iron and erythropoietin is highly effective, but frequently leads to ferritin levels which are much higher than those seen in the general population. High ferritin concentrations raise concern about the potential toxicity of increased body iron stores. PATIENTS AND METHODS: We retrospectively evaluated parameters of iron metabolism over a 4-year period among all our chronic hemodialysis patients who had been receiving intravenous iron and erythropoietin. Initially, patients received intermittent infusions of 300 mg intravenous iron x 3 doses for a low ferritin or low percent saturation of total iron binding capacity (TIBC), but this protocol was subsequently changed to weekly or biweekly infusions of 50-100 mg. RESULTS: We observed an improvement in average hemoglobin values, modest increases in serum iron and saturation of iron binding capacity, and a 125% increase in ferritin levels over 4 years. TIBC decreased. Overall, ferritin values increased 79 microg/l for each 1% increase in TIBC saturation. Ten patients with ferritin concentration greater than 1,000 pg/l received a three month course of vitamin C with no decline in the ferritin concentration. CONCLUSION: Current protocols for iron delivery may result in progressive increases in ferritin levels. Concern about the risks of iron overload should temper the quantity of iron used in dialysis programs.     

A prospective crossover trial comparing intermittent intravenous and continuous oral iron supplements in peritoneal dialysis patients.

BACKGROUND: Concomitant iron supplementation is required in the great majority of erythropoietin (Epo)-treated patients with end-stage renal failure. Intravenous (i.v.) iron supplementation has been demonstrated to be superior to oral iron therapy in Epo-treated haemodialysis patients, but comparative data in iron-replete peritoneal dialysis (PD) patients are lacking. METHODS: A 12-month, prospective, crossover trial comparing oral and i.v. iron supplementation was conducted in all Princess Alexandra Hospital PD patients who were on a stable dose of Epo, had no identifiable cause of impaired haemopoiesis other than uraemia, and had normal iron stores (transferrin saturation >20% and serum ferritin 100-500 mg/l). Patients received daily oral iron supplements (210 mg elemental iron per day) for 4 months followed by intermittent, outpatient i.v. iron infusions (200 mg every 2 months) for 4 months, followed by a further 4 months of oral iron. Haemoglobin levels and body iron stores were measured monthly. RESULTS: Twenty-eight individuals were entered into the study and 16 patients completed 12 months of follow-up. Using repeated-measures analysis of variance, haemoglobin concentrations increased significantly during the i.v. phase (108+/-3 to 114+/-3 g/l) compared with each of the oral phases (109+/-3 to 108+/-3 g/l and 114+/-3 to 107+/-4 g/l, P<0.05). Similar patterns were seen for both percentage transferrin saturation (23.8+/-2.3 to 30.8+/-3.0%, 24.8+/-2.1 to 23.8+/-2.3%, and 30.8+/-3.0 to 26.8+/-2.1%, respectively, P<0.05) and ferritin (385+/-47 to 544+/-103 mg/l, 317+/-46 to 385+/-47 mg/l, 544+/-103 to 463+/-50 mg/l, respectively, P=0.10). No significant changes in Epo dosages were observed throughout the study. I.v. iron supplementation was associated with a much lower incidence of gastrointestinal disturbances (11 vs 46%, P<0.05), but exceeded the cost of oral iron treatment by 6.5-fold. CONCLUSIONS: Two-monthly i.v. iron infusions represent a practical alternative to oral iron and can be safely administered to PD patients in an outpatient setting. Compared with daily oral therapy, 2-monthly i.v. iron supplementation in PD patients was better tolerated and resulted in superior haemoglobin levels and body iron stores.     

The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney disease

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

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.     

Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia.

BACKGROUND: Inadequate iron mobilization and defective iron utilization may cause recombinant erythropoietin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. We have demonstrated that intravenous ascorbic acid (IVAA), but not intravenous iron medication, can effectively circumvent the functional iron-deficient erythropoiesis associated with iron overload in HD patients. However, it is uncertain whether all HD patients with hyperferritinemia will consistently respond to IVAA and which index may indicate functional iron deficiency in the special entity. Therefore, a prospective study was conducted to establish the guidelines for IVAA adjuvant therapy. METHODS: Sixty-five HD patients with serum ferritin levels of more than 500 microgram/liter were recruited and divided into the control (N = 19) and IVAA (N = 46) groups. IVAA patients with a hematocrit (Hct) of less than 30% received 300 mg of ascorbic acid three times per week for eight weeks. Controls had a Hct of more than 30% and did not receive the adjuvant therapy. Red blood cell and reticulocyte counts, iron metabolism indices, erythrocyte zinc protoporphyrin (E-ZPP), and the concentrations of plasma ascorbate and oxalate were examined before and following the therapy. RESULTS: Thirteen patients (four controls and nine IVAA patients) withdrew by the end of the study. Eighteen patients had a dramatic response to IVAA with a significant increase in their hemoglobin and reticulocyte index and a concomitant 24% reduction in rEPO dose after eight weeks. This paralleled a significant rise in serum iron and transferrin saturation (TS) and a fall in E-ZPP and serum ferritin (baselines vs. 8 weeks, serum iron 68 +/- 37 vs. 124 +/- 64 microgram/dl, TS 27 +/- 10 vs. 48 +/- 19%, E-ZPP 123 +/- 44 vs. 70 +/- 13 micromol/mol heme, and serum ferritin 816 +/- 435 vs. 587 +/- 323 microgram/liter, P < 0. 05). Compared with responders, mean values of hemoglobin, rEPO dose, iron metabolism parameters, and E-ZPP showed no significant changes in controls (N = 15) and in non-responders (N = 19). Thirty-seven patients (18 responders and 19 non-responders) were further analyzed by receiver operating characteristic curves to seek the criteria for prediction of a response to IVAA treatment. The results showed that E-ZPP at a cut-off level of more than 105 micromol/mol heme and TS at a level of less than 25% were more specific to confirm the status of functional iron deficiency in iron-overloaded patients. The two criterion values had the highest accuracy to predict a response to treatment. CONCLUSIONS: Functional iron-deficient erythropoiesis plays a role in rEPO-hyporesponsive anemia in HD patients with hyperferritinemia. IVAA may be an adjuvant therapy for rEPO in these patients, and E-ZPP of more than 105 micromol/mol heme and TS of less than 25% should be used to guide the IVAA treatment.     

Efficacy of hepatic computed tomography to detect iron overload in chronic hemodialysis

The diagnostic efficacy of hepatic computed tomography density (HCTD) in comparison with serum ferritin for the detection of iron overload was investigated in uremic patients on maintenance hemodialysis (HD) and in patients with idiopathic hemochromatosis (IHC). Ten IHC patients, 38 HD patients and 40 healthy subjects underwent the CT scanning of the liver and determination of percent saturation of transferrin, serum ferritin concentration and HLA typing. Liver iron content was determined by histochemical grading and direct measurement of liver iron concentration either in IHC patients or in HD patients. Nineteen HD patients were considered to have iron overload on the basis of liver iron concentration exceeding 3.6 mumol/100 mg dry weight. The mean +/- SD values of HCTD in healthy subjects, IHC patients, HD patients with iron overload and without iron overload were 60.2 +/- 5.6, 79 +/- 5.6, 71.4 +/- 3.6, 58 +/- 3.8 Hounsfield units, respectively. HCTD showed positive correlations with liver iron concentration and serum ferritin either in IHC patients or in HD patients. The analysis of the diagnostic efficacy of HCTD in comparison with serum ferritin for the detection of excessive hepatic iron in HD patients demonstrated that HCTD had higher sensitivity, specificity, positive and negative predictive values. Cut-off points were arbitrarily fixed to 66 Hounsfield units for HCTD, 400 micrograms/liter for serum ferritin and 3.6 mumol/100 mg dry weight for liver iron concentration. Seventeen HD patients who possessed the histocompatibility antigens associated with IHC, namely HLA-A3 and/or HLA-B7 and/or HLA-B14, had liver iron concentration, serum ferritin and HCTD values higher than those of the HD patients without these "hemochromatosis alleles".(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

蔗糖铁注射液联合红细胞生成素治疗肾性贫血的临床观察

目的 观察蔗糖铁注射液联合红细胞生成素治疗伴有缺铁的维持性血液透析肾性贫血患者疗效及安全性.方法 选取尿毒症维持性血液透析患者46例,按随机数字表法分为治疗组(26例)和对照组(20例).治疗组采用静脉滴注蔗糖铁100 mg,每周2次,总量达1000 mg改为100 mg,每周1次;对照组采用口服乳酸亚铁0.2 g,每日3次.红细胞生成素的使用剂量和方法两组相同,总疗程均为10周.结果 经治疗后治疗组患者血红蛋白、红细胞压积、血清铁蛋白水平与对照组比较差异有统计学意义(P<0.05).结论 蔗糖铁联合红细胞生成素治疗肾性贫血疗效优于口服铁剂联合红细胞生成素治疗.不良反应发生率更低,可作为肾性贫血患者长期补铁的方法之一.     

Soluble transferrin receptor is correlated with erythropoietin sensitivity in dialysis patients.

BACKGROUND: Iron deficiency is the most common cause of erythropoietin (EPO) resistance in dialyzed patients with renal anemia. Subclinical or functional iron deficiency is difficult to diagnose in these patients. The soluble transferrin receptor (sTf-R) is considered as a sensitive and specific indicator of bone marrow iron availability. PATIENTS AND METHODS: To evaluate the clinical usefulness of this novel marker, we investigated relationships between EPO requirements and various hematological and biochemical parameters of erythropoiesis in 27 pediatric end-stage renal failure patients treated by hemodialysis (HD, n = 11) or chronic peritoneal dialysis (PD, n = 16). Iron was substituted intravenously once or twice per week in HD, and by daily oral administration to PD patients. Serum sTf-R concentrations were measured by an enzyme-linked immunosorbent assay. Serum ferritin and transferrin concentrations were determined using nephelometric assays. Hemoglobin and iron levels were estimated by automated procedures. RESULTS: While neither transferrin saturation nor serum ferritin concentrations were indicative of EPO requirements, a highly significant correlation between the EPO efficacy index (EPO dose divided by hemoglobin concentration) and sTf-R was observed (r = 0.65, p = 0.001). The intravenous iron substitution in HD patients was associated with higher ferritin concentrations compared to the orally substituted PD patients (280+/-100 ng/ml vs. 124+/-83 ng/ml, p<0.002). In contrast, sTf-R concentrations were similar in both treatment groups (25.7+/-7.7 nM vs. 27+/-10.8 nM, n.s.), as were hemoglobin concentrations and EPO requirements. CONCLUSION: Our results suggest that sTf-R is a more sensitive indicator of functional iron deficiency and impaired EPO responsiveness than serum ferritin or transferrin saturation in dialyzed patients. Intensified iron substitution to patients with elevated sTf-R concentrations may considerably improve the cost efficacy of EPO treatment.     

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.     

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.     

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.     

Oral Iron for Patients Receiving Dialysis: What is the Evidence?

This review aims to summarize the available evidence of the effectiveness of oral iron in patients receiving dialysis. Four small randomized controlled trials (105 evaluated patients) compared oral iron supplements with placebo or no treatment; hemoglobin and ferritin levels did not differ significantly between groups at the end of the studies, while transferrin saturation levels fell in the placebo group in two studies. One trial (46 evaluated patients), comparing different ferrous iron preparations, found that hemoglobin levels and iron indices were maintained, but not increased. Another trial (54 evaluated patients) compared heme iron polypeptide with ferrous sulfate; hemoglobin and transferrin saturation levels remained stable with both agents, but ferritin levels fell with heme iron polypeptide, but not ferrous sulfate. Two observational studies found that iron supplements can maintain hemoglobin and iron indices. Oral iron supplements were poorly tolerated. These sparse data suggest that oral iron is of little or no benefit in raising hemoglobin and iron indices in patients receiving dialysis. Further data are required to determine if oral iron can maintain adequate iron indices following iron replenishment using intravenous iron supplements.