Ascorbic acid does not augment the restoration effect of iron treatment for empty iron stores in patients after gastrointestinal surgery

The effect of a 6-week combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) on the empty iron stores in 20 patients after gastrointestinal surgery was examined from changes of serum ferritin. One group of 20 patients with similar clinical characteristics served as controls. The treatment replaced the empty iron stores. Since mean serum ferritin concentrations increased from 9 +/- 8 to 29 +/- 11 micrograms/l (P less than 0.001) in males and from 8 +/- 8 to 26 +/- 10 micrograms/l (P less than 0.001) in the females. Also blood hemoglobin and serum iron concentrations increased significantly (P less than 0.01). Among the controls there were no marked changes in serum ferritin, blood hemoglobin or serum iron concentrations. However, the increase of serum ferritin caused by this combined treatment was similar with that caused previously by pure ferrous sulfate treatment. Thus, it is considered that the combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) restores the empty iron stores in patients after gastrointestinal surgery, but that the increase is not augmented by the ascorbic acid. Thus, a pure iron therapy is recommended to fill up the empty iron stores in these patients.     

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.     

Clinical and histologic features of iron-related bone disease in dialysis patients

Forty-eight dialysis patients undergoing bone biopsy were analyzed for clinical history, blood biochemical values, bone histologic findings, bone aluminum content (BAC), bone iron content (BIC), bone iron stores, and histochemical staining of bone aluminum and bone iron. Four patients had significant trabecular bone iron staining alone; eight patients had significant bone iron and bone aluminum staining; 13 patients had significant bone aluminum staining alone; and 23 patients showed no significant bone aluminum or iron staining. Patients with significant bone iron staining were younger (37.4 +/- 5.3 years v 53.2 +/- 2.3 years, P less than 0.01, mean +/- SEM) and were more likely to be anephric (P less than 0.001) and to have a history of prior renal transplantation (P less than 0.10). The 12 patients with significant bone iron staining had received more blood transfusions than those without bone iron staining (96 +/- 22.8 U v 22 +/- 5.8 U, P less than 0.005). Patients with bone iron accumulation had higher levels of serum ferritin (3,594 +/- 1,138.4 micrograms/L [ng/mL] v 265 +/- 60.1 micrograms/L, P less than 0.01) and lower levels of immunoreactive parathyroid hormone (iPTH) (349 +/- 150 microLEq/mL v 1,801 +/- 397 microLEq/mL [386 +/- 166 pmol/L v 1,990 +/- 439 pmol/L], P less than 0.005). BIC was also higher in these patients (1,008 +/- 149 micrograms iron/g bone v 300 +/- 46.5 micrograms iron/g bone, P less than 0.001) and higher than normal BIC (256 +/- 44.2 micrograms iron/g bone, eight normals). Bone marrow iron stores were positively related to serum ferritin levels (P less than 0.01) and trabecular bone iron staining (P less than 0.10). All 13 patients with osteomalacia demonstrated significant bone aluminum staining; seven of these patients demonstrated concomitant significant iron staining. Fourteen of 15 patients with severe hyperparathyroidism showed no significant iron or aluminum staining. Our data indicate that iron will probably not accumulate within bone until all other storage sites (eg, bone marrow) are fully saturated. The presence of lower levels of iPTH in iron-overloaded patients raises the possibility that iron overload may induce a state of relative hypoparathyroidism. The most important determinant for the presence of osteomalacia seems to be the presence of significant aluminum staining. No specific bone histologic finding was related to the presence of bone iron staining, but the rarity of isolated significant bone iron staining makes it difficult to evaluate bone histologic diagnoses that might be solely attributable to iron.     

Nutritional anaemia in pregnant coloured women in Johannesburg

A nutritional anaemia survey was carried out in 224 pregnant coloured first-time attenders at Coronation Hospital antenatal clinic in Johannesburg during the second quarter of 1986. None had received any form of nutritional supplementation during pregnancy. Haemoglobin concentrations less than 11 g/dl were present in 18.9% of women in the third trimester of pregnancy, while 64% had a saturation of transferrin value of less than 16% and 68% a serum ferritin level less than 12 micrograms/l. Calculations suggested that mean iron stores in the first trimester were 228 mg, with 37.5% of women having absent stores. Comparable figures in the second and third trimesters were 74 mg and -92 mg respectively. The fact that many were iron deficient in the first trimester indicates a high frequency of iron deficiency in non-pregnant women in this population group. Although 20.8% of the women had red cell folate values below the normal range for non-pregnant subjects, folate deficiency did not appear to be a significant problem. Vitamin B12 deficiency was very uncommon.     

Human recombinant erythropoietin treatment in transfusion dependent anemic patients on maintenance hemodialysis

Six anemic hemodialysis patients dependent on regular blood transfusions and with massive iron overload were treated with recombinant human erythropoietin (r-huEPO). The effect on absolute reticulocyte count, hemoglobin and serum ferritin was studied during a twenty-week period. Red-cell volume and red-cell life span were measured with 51Cr-tagged erythrocytes at baseline and after twenty weeks of r-huEPO. Absolute reticulocyte counts and hemoglobin concentration rose markedly (from 55.6 +/- 31.2 to a maximum of 174.9 +/- 31.0 x 10(9)/l at 4 weeks and from 6.8 +/- 0.3 to a maximum of 11.2 +/- 1.3 g/dl at 12 weeks, respectively, p less than 0.001) without any further need for transfusions. Red-cell volumes increased concomitantly (from 58 +/- 4 to 81 +/- 11% of normal, p less than 0.005), in spite of a persistent shortening of red-cell life span (45 +/- 18 and 47 +/- 4 days before and after r-huEPO). Markedly elevated serum ferritin concentrations indicating iron overload decreased slowly from 3,550 +/- 1,615 to 2,721 +/- 1,506 micrograms/l (p less than 0.05). It is concluded that r-huEPO is very effective in treating the anemia of patients maintained on hemodialysis. The favorable effects on hemoglobin and red-cell volumes occur in spite of persistent hemolysis and lead to a slow reduction of iron overload.     

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.     

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.     

Serum ferritin levels after renal transplantation: a prospective study

A prospective study was made of the evolution of serum ferritin levels in 112 renal transplant recipients with good graft function. The rise in hemoglobin value is accompanied by a decrease in basal serum ferritin levels which are lowest at the sixth month: 54.9 (2-1,516) vs. 109.6 (21-4,420) micrograms/l, p less than 0.001 (Xg and range). After this time, ferritin values increase, although they do not reach basal levels. Evolution after transplantation is mainly determined by the previous state of iron stores at the time of transplantation. While in the patients with high basal serum ferritin values these gradually decreased during the follow-up period, patients with low basal serum ferritin levels tend to replenish their iron stores after renal transplantation. These differences disappear at the third year when serum ferritin values are similar in all groups. An association between persistence of posttransplant anemia and low serum ferritin levels is observed. This event is not clinically relevant as anemia disappears in almost all cases and dietary iron is enough to normalize serum ferritin levels.     

Anaemia in pregnant Indian women in Johannesburg

A study was performed in 100 subjects to determine the prevalence and cause of anaemia in pregnant Indian women in the Johannesburg area. The geometric mean serum ferritin concentration in all three trimesters of pregnancy was below 12 micrograms/l, with 43.3% of women in the first, 48.6% in the second and 80.0% in the third trimester having concentrations below this value. Estimation of body iron stores revealed a mean deficit of 265 mg iron in subjects in the third trimester, 20% of whom had iron deficiency anaemia. No difference in iron status was demonstrable in subjects from different religious backgrounds. Folate and vitamin B12 nutrition was adequate. Three subjects were diagnosed as being beta-thalassaemia heterozygotes. The findings underline the need for routine iron supplementation of pregnant Indian women in the Johannesburg area.     

Treatment of a patient with end-stage renal disease, severe iron overload and ascites by weekly phlebotomy combined with recombinant human erythropoietin

A 41-year-old hemodialyzed woman developed ascites and was found to have secondary iron overload. The dose of administered iron was approximately 11-12 g, and her serum ferritin level was 15,000 ng/ml (15,000 micrograms/l). There were no signs of congestive heart failure, fluid overload, or liver cirrhosis. A program of weekly phlebotomy combined with recombinant human erythropoietin (rhEPO) therapy was tried to eliminate the iron congestion. After 9 months of this therapy, about 5 g of iron had been removed. The ascites completely disappeared, and her serum ferritin level fell to 5,800 ng/ml (5,800 micrograms/l). This suggests that such combined therapy would be useful when iron overload must be corrected rapidly. Before therapy, the sterile ascitic fluid showed exudative characteristics with 3.7 g/dl (37 g/l) of total protein. The serum-ascites albumin difference was 0.6 g/dl (6 g/l), and the fluid contained 1,400 inflammatory cells/mm3 (1.4 X 10(9)/l). Notably, the serum-ascites albumin difference increased in parallel with iron elimination. These findings suggested that iron deposition may have played a role in changing the permeability of the peritoneum, or in impairing lymphatic drainage, both of which are presumed to be pathogenetic factors of nephrogenic ascites.     

Serum ferritin levels are increased in patients with glomerular diseases and proteinuria.

BACKGROUND: Ferritin is a high molecular weight protein which reflects body iron stores, but may also rise in the case of an acute phase response. Recently, ferritin has been identified as a predictive factor in the development and progression of atherosclerosis. This is the first report on serum ferritin levels in patients with proteinuria. METHODS: We have analysed the data of 142 male patients with a glomerular disease, and proteinuria exceeding 1 g/day. In all patients, we measured various parameters related to proteinuria, serum ferritin and serum iron. Serum beta2-microglobulin and the Modification of Diet in Renal Disease (MDRD) equation were used as measures of the glomerular filtration rate (GFR). RESULTS: Mean age (+/-SD) was 46+/-15 years, MDRD-GFR 57+/-25 ml/min/1.73 m2 and median proteinuria 8.0 g/day [interquartile range (IQR) 3.6-13]. Serum albumin (29+/-9 g/l) and transferrin levels (1.7+/-0.5 g/l) were low, and cholesterol levels were elevated (median 7.3, IQR 5.9-9.5 mmol/l). Median serum ferritin was 148 microg/l (IQR 89-282), and exceeded 280 microg/l, the upper limit of normal, in 36 patients (25%). Elevated serum ferritin levels could not be explained by an acute phase response as determined by C-reactive protein, or haemochromatosis (DNA analysis). Regression analysis showed an independent relationship between ferritin levels and serum cholesterol, GFR and serum transferrin. CONCLUSIONS: Serum ferritin levels are elevated in patients with overt proteinuria. The independent negative relationship between serum ferritin and transferrin points to a specific process and suggests that increased production of ferritin may compensate for the loss of the iron-binding protein transferrin, thus reducing the amount of free iron. Further studies are needed to elucidate the role of ferritin in patients with proteinuria, especially because of the suggested association between ferritin and atherosclerosis.     

Nutritional anaemia in 11-year-old schoolchildren in the western Cape

A nutritional anaemia survey was carried out on 610 11-year-old coloured, black and white schoolchildren in urban and rural communities in the western Cape. The mean (+/- 1 SD) haemoglobin concentration was 13.0 +/- 1.2 g/dl. The coloured and black subgroups considered together had a significantly lower mean haemoglobin concentration than the white subgroup (12.8 +/- 1.2 g/dl v. 13.4 +/- 1.0 g/dl) (F = 37.47; P less than 0.0001). The urban population as a whole had a significantly lower geometric mean (1 SD range) serum ferritin concentration than the rural population (25.6 (13.5-48.6) micrograms/l v. 34.1 (21.3-54.6) micrograms/l) (F = 42.94; P less than 0.0001). The lowest geometric mean serum ferritin values were found in the urban coloured (23.1 (11.5-46.4) micrograms/l) and urban black schoolchildren (23.7 (13.2-42.6) micrograms/l), with figures of less than 12 micrograms/l in 11.7% and 12.5% respectively. Although 28% of the children had red cell folate values below the recommended lower limit of normal (175 ng/ml), probability plot analysis of the data suggested that folate deficiency was not a major problem in the study population. The calculated daily iron and folate intakes were below the age-related recommended dietary allowance (RDA) in all the subgroups, yet anaemia was relatively uncommon. These findings suggest that the RDA values are too high. Overall the prevalence of nutritional anaemia was low and only the urban coloured subgroup showed significant second populations with low haemoglobin and serum ferritin measurements.     

Iron overload in haemodialysis patients increases the risk of bacteraemia: a prospective study

The incidence of bacteraemia in relation to the degree of transfusional iron overload was studied prospectively in patients from one haemodialysis unit over a 2-year period, with a total follow-up of 181.3 patient-years in 158 patients. Every 3 months, the patients were classified according to the serum ferritin in one of three groups: less than 500, 500-1000 or greater than 1000 micrograms/l. Twenty-nine episodes of bacteraemia were recorded over 181.3 patient-years (yearly incidence of 0.160). The yearly incidence of bacteraemia was 0.1173 and 0.1101 for ferritin less than 500 and 500-1000 micrograms/l (no significant difference), with a cumulative incidence for both groups of 0.1164. In the ferritin greater than 1000 micrograms/l group, the incidence was 0.3404 (P less than or equal to 0.005 versus the ferritin less than or equal to 1000 micrograms/l group). After stratification for patient's age (at inclusion in the study) and duration of haemodialysis therapy, the higher incidence of bacteraemia in the ferritin greater than 1000 versus less than or equal to 1000 micrograms/l groups persisted (P less than or equal to 0.005). This prospective study confirms previous retrospective studies in showing that acquired transfusional iron overload in haemodialysis is associated with a greater risk of bacteraemia.     

Low serum iron concentration in acute cholecystitis. A discriminator of severity of infection

This study demonstrates that serum iron levels are significantly depressed during acute cholecystitis. Mean admission serum iron concentration for 18 patients who had required emergency cholecystectomy within 48 hours of hospitalization was 40.9 micrograms/100 ml +/- 27.08 (7.32 mumol/l) while for 108 patients who had undergone elective cholecystectomy in the same 18-month period the mean concentration was 90.5 micrograms/100 ml +/- 34.27 (16.2 mumol/l); a mean difference of 49.6 micrograms/100 ml (3.92 mumol/l) (t = 5.8395, P less than 0.00001). Mean serum iron level in seven patients with culture positive acute cholecystitis was 26.4 micrograms/100 ml +/- 10.45 (4.73 mumol/l), significantly different (P less than 0.05) than in 11 patients with culture negative cholecystitis, 50.3 micrograms/100 ml +/- 30.41 (9.00 mumol/l). Admission serum iron level averaged 25.6 micrograms/100 ml (4.58 mumol/l) in three patients with gangrenous gallbladders and was 18 micrograms/100 ml (3.22 mumol/l) in one patient with empyema of the gallbladder. Determination of serum iron level may help distinguish patients with significant infections requiring urgent surgery from patients with biliary colic.     

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.     

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.     

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.     

Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients

BACKGROUND: Iron deficiency is the most common cause of suboptimal response to recombinant human erythropoietin (rHuEPO) in chronic hemodialysis (HD) patients. Iron supply can correct this situation, however, optimal dosage, route of administration, and monitoring of iron status during rHuEPO therapy in maintenance HD patients remains controversial. METHODS: We conducted a 12-month intravenous iron substitution trial in 149 iron-replete chronic HD patients receiving subcutaneous rHuEPO therapy. The available iron pool was maintained with 100 mg iron every 2 weeks or 1 month depending on serum ferritin and transferrin saturation levels, the rHuEPO dosage titrated depending on hematocrit (Hct) levels. RESULTS: After 12-month protocol, the Hct increased (28.7 +/- 4.1 vs 27.7 +/- 2.6, p = 0.003), rHuEPO requirement reduced 25% (46.1 +/- 28.9 vs 61.5 +/- 67.8 U/kg/week, p = 0.006), serum ferritin increased (1,383 +/- 727 vs 930 +/- 857 ng/ml, p < 0.001), so did the transferrin saturation (36.1 +/- 12.7 vs 27.5 +/- 12.8%, p < 0.001). The serum albumin decreased slightly but reached statistical significance (4.1 +/- 0.48 vs 4.2 +/- 0.36 g/dl, p = 0.006), so did the cholesterol levels (166 +/- 41 vs 173 +/- 38 mg/dl, p = 0.044) and pre-dialysis creatinine (11.3 +/- 2.3 vs 11.5 +/- 2.4 mg/dl, p = 0.015). Besides, the iPTH levels did not interfere with the rHuEPO dosage reduction and Hct increment in our patients. CONCLUSION: We conclude that maintaining high levels of serum ferritin and transferrin saturation could further reduce the requirement of rHuEPO in chronic HD patients, but the long-term effect of iron overloading to patients' nutritional status must be further evaluated in contrast to the economic saving.     

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 repeated intravenous iron administration in haemodialysis patients on serum 8-hydroxy-2'-deoxyguanosine levels.

BACKGROUND: Iron supplementation is a mainstay for management of renal anaemia in patients receiving haemodialysis (HD). Although it is well known that a single intravenous iron (IVIR) administration transiently enhances oxidative stress in HD patients, the consequence of repeated IVIR administration is still unknown. This study aims to clarify the time course of changes in serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, during a period of repeated IVIR administration in HD patients. METHODS: Twenty-seven patients (62+/-14 years and 23 males) on long-term HD participated in this study. All patients had been on HD more than 6 months and none had received a blood transfusion or iron therapy in previous 6 months. The patients were divided into three groups according to the baseline haematocrit (Ht) and serum ferritin (FTN) levels as a marker of body iron stores: IVIR group (Ht<30% and FTN<100 ng/ml; n=7); High FTN group (Ht>or=30% and FTN>or=100 ng/ml; n=11); and low FTN group (Ht>or=30% and FTN<100 ng/ml; n=9). The IVIR group patients received 40 mg of ferric saccharate i.v. after each HD session until Ht increased by 5%. Serum 8-OHdG and other parameters were prospectively monitored for 10 weeks. RESULTS: At baseline, the serum ferritin level was independently associated with 8-OHdG in a multiple regression model (total adjusted R2=0.47, P<0.01). All patients in the IVIR group achieved the target Ht level during the study. IVIR administration resulted in significant increases in 8-OHdG levels (0.22+/-0.07-0.50+/-0.16 ng/ml: baseline to 10 week) as compared with both the high FTN group (0.52+/-0.20-0.58+/-0.28 ng/ml) and the low FTN group (0.39+/-0.11-0.36+/-0.11 ng/ml) (ANOVA for repeated measures P<0.01). Additionally, serum 8-OHdG and serum ferritin changed in the same manner. CONCLUSIONS: Repeated IVIR administration for HD patients was associated with signs of increased oxidative DNA injury, as reflected by increased serum levels of 8-OHdG. As these changes were accompanied by increased serum ferritin levels, excess body iron stores might play an important role in oxidative stress.