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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1999  |  Volume : 10  |  Issue : 1  |  Page : 21-25
Maintenance Intravenous Iron Therapy in Hepmodialysis Patients Receiving Recombinant Human Erythropoientin

Department of Nephroogy, King Fahad National Guard Hospital, Riyadh, Saudi Arabia

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Iron Supplementation is crucial in raising hematocrit as well as dosage saving for recombinant human erythropoietin therapy (rHuEPO) in maintenance hemodialysis patients. Intravenous iron has proved to be both safe and efficacious in this patient's population. However, the exact iron requirement has not been worked our. In this study we found that 1000 mg of element iron (given as iron saccharate) per moth was effective in maintaining hematocrit and hemoglobin at 33% and 110 gm/L respectively, and reducing the erythropoietin (EPO) dosage by about 20% in maintenance hemodialysis patients who were iron-replete. The serum ferritin increased from 219±144 to 320±234 µg/L (P<0.05). There were no major side effects and patients tolerated the monthly iron therapy well. Our study suggests that intravenous iron saccharate (100 mg/month) is effective and safe in patients on maintenance hemodialysis receiving RHUEPO.

Keywords: Recombinant human erythropoietin, Maintenance hemodialysis, Intravenous iron therapy, Serum ferritin.

How to cite this article:
Romeh SA, Huraib S, Murray N, Tanimu D, Flaiw A, Iqbal A, Al Ghamdi G, Quadri K. Maintenance Intravenous Iron Therapy in Hepmodialysis Patients Receiving Recombinant Human Erythropoientin. Saudi J Kidney Dis Transpl 1999;10:21-5

How to cite this URL:
Romeh SA, Huraib S, Murray N, Tanimu D, Flaiw A, Iqbal A, Al Ghamdi G, Quadri K. Maintenance Intravenous Iron Therapy in Hepmodialysis Patients Receiving Recombinant Human Erythropoientin. Saudi J Kidney Dis Transpl [serial online] 1999 [cited 2021 Jan 27];10:21-5. Available from: https://www.sjkdt.org/text.asp?1999/10/1/21/37297

   Introduction Top

Recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of anemia in patients with end-stage renal diseases (ESRD). [1] However, only about one-half of such patients treated with rHuEPO have a hematocrit greater than 30%.[2] In this regards, many factors have been identified that blunt the effectiveness of rHuEPO including inflammation, infection,[3],[4] bone marrow fibrosis, [5] aluminum intoxication6 and inadequate dialysis. [7] More important is the inadequate avail­ability of iron to optimize erythopoiesis. [8],[9] The prevalence of iron deficiency in the dialysis patients during rHuEpo therapy has been estimated at 45% to 90%.[10],[11],[12],[13] Successful therapy of animal mandates that iron stores be closely monitored and iron deficiency be appropriately treated. Intensive iron management can be expected to result in a greater proportion of patients achieving target levels of hematocrit. Oral iron is the treatment of choice for replacement of iron stores in non-uremic patients. The efficacy of oral iron is patients with ESRD may be hindered by many factors, which would tend to decrease its intestinal absorption. Such factors are the presence of phosphate bindrs, [14] use of medications that diminish gastric acidity, [15] intolerance to intake of iron on an empty stomach, [16] and inability to administer vitamin C supplements that are helpful in non-uremic patients increasing the absorption of oral iron. [16] To circumvent this problem, we switched all our hemodialysis patients who were receiving rHuEPO to maintenance intravenous iron therapy. In this article, were report our experience after 12 months of implanting such a protocol.

   Patients and Methods Top


In February 1996, all regular dialysis patients in our unit who were receiving rHuEPO treatment and were on oral iron supplements (ferrous sulfate 200mg tid) were switch to monthly intravenous iron saccharate 100 mg and the oral iron was discontinued.

This intravenous iron dosage was calculated based on the presumptive average lose of about 25 ml of blood during each dialysis session, i.e. about 300 ml of blood per month which translates to about 100 mg elemental iron. Serum ferritin, serum iron, and total iron binding capacity (TIBC) were measured every three months.

However, because of logistic reasons, not all patients had serum iron and TIBC at the beginning of the study. Patients who were iron depleted, wit serum ferritin below 100 µg, were given 1000 mg of iron saccharate over 10 successive dialysis sessions.


Forty patients (19 males, 21 females) were included in this report and all of them met the following criteria.

(a) They were regularly followed at our unit for at least one year before the start of intravenous iron therapy and had fairly stable rHuEPO dosage;

(b)Were clinically stable i.e. no evidence of chronic inflammatory disease such as tuberculosis and were compliant to the dialysis protocol and other therapy;

(c) Had adequate nutritional status as evidenced by serum albumin more than 35 g/L;

(d)None had severe osteitis fibrosa (intact PTH assay less than 500 pg/ml);

(e) None had evidence of severe iron depletion i.e serum ferritin below 100 µg/L;

(f) None had evidence of aluminum toxicity as serum aluminium levels were very low (below 1 µg/L)

Fourteen out of the 40 patients were diabetic; the mean age of our patients was 54 ± 11 kg. The mean duration on regular hemodialysis was 40 ± 22 months with a range between 15 and 108 months.

   Dialysis Protocol Top

All patients were dialyzed between 31/2 to 4 hours three times per week using 1.5 sq. meter hollow fiber cellulosic dialyser and Century III machines. The dialysate was bicarbonate with 140 mEq/L sodium, 35 mEq/L bicarbonate, and 3 mEq/L calcium.

Monthly laboratory investigations were monitored and adequacy of dialysis was ensured by monitoring the urea reduction ratio (UPR) which was kept more than 65% in all patients. Vascular access monitoring was also ensured to give a blood flow of 300 ml/min or more.

   Erythropoietin Protocol Top

rHuEPO therapy was administered according to the following protocol. The starting dose was 50 units/kg subcutaneously three tines weekly which was increased every 2 weeks by 25 units/kg until the target hematocrit of 30% was reached, then the patient was converted to weekly dose which was one third of the previous total dosage. If the hematocrit reached 36% or above the dose was further reduced to one-half, and rHuEPO was with­held if the hematocrit reached above 38%.

   Statistics Top

The results are expressed as mean ± standard deviation. Paired Student's t-test was used to compare the values in the same patients before and after therapy. P value below 0.05 was considered to be significant.

   Results Top

[Table - 1] summarizes the results of the parameters, measured while on oral iron therapy and at the end of 12 months of receiving intravenous iron. AS shown, the change in hemoglobin and hematocrit were insignificant. However, the rHuEPO dosage was significantly reduced from 6600 ± 3000 units per weekly dosage to 5200 ± 2800 units (p<0.05). This also applied to the dosage as expressed in units/kg/week, which was decreased from 111 ± 55units/kg to 88 ± 47, representing a 21% reduction.

   Discussion Top

Many dialysis unit shave recently started using intravenous iron in place of oral iron for the long-term maintenance of iron stores. [17],[18] In one recently published clinical trail, patients were randomized receive either daily oral iron of weekly intravenous iron therapy. [19] The patients were iron­replete as in our population and the dose of intravenous iron dextran was 200 mg per week. After four months of follow-up, the mean hematocrit rose about 3% and the mean rHuEPO dose was reduced by 46% in patients treated with intravenous iron. However, the dose of intravenous iron was too high as the serum ferritin increased to unacceptable levels with the risks of iron overload and tissue toxicity. For this reason, we adopted to give only 100 mg of iron saccharate per month our iron-replete patients and it is interesting that serum ferritin, though it increased about 50%, did not exceed the acceptable limits even after one year. The mean hematocrit did not change very much in our patients since in our protocol the dosage of rHuRPO was decreased once the hematocrit reached 30% and further decreased at 36%. However, there was an approximately 20% reduction in the weekly rHuEPO dosage and this maintained for one year.

All our patients tolerated the intravenous iron saccharate quite well and no side effects including anaphylactic reactions, severe pain at injection site, severe myalgia or arthralgia were encountered. Additionally there was no need to discontinue the monthly iron injection in any patients. It appears that some of the adverse reactions to intravenous iron could be related to the dose per administration. [20]

In this regard, a recent multicenter study evaluated 573 hemodialysis patients and found a serious reaction rate (permanent disability, immediate risk of death or need for hospitalization) of 0.7% with no deaths. [21] Anaplylactoid reactions such as dyspnea, wheezing, chest pain, hypotension, urticaria, or angioedema occurred in 1.7% of these patients. Iron dextran was used in this study and it is quite plausible that with iron saccharate, which was used in our study, the incidence of reactions could be even lower.

In summary, we found that discontinuing oral iron and replacing it with monthly 100 mg iron saccharate is safe and effective. With this approach, our patients were able to avoid taking three tablets of iron on an empty stomach daily and we were able to save about 20% in terms of the dosage of rHuEPO without affecting the target hematocrit. Moreover, the cost of the intravenous therapy is quite comparable to the oral form.

   References Top

1.Eschbach JW, Kelly MR, Haley NR, Abels RI, Adamson JW. Treatment of the anemia of progressive renal failure with recombinant heman erythropoietin. N Engl J Med 1989;321:158-63.  Back to cited text no. 1  [PUBMED]  
2.Powe Nr, Griffiths RI, Greer JW, et al. Early dosing practices and effectiveness of recombinant human erythropoietin. Kidney Int 1993;43:1125-33.  Back to cited text no. 2  [PUBMED]  
3.Macdougall IC, Coles GA, Willimans JD. Inhibition of a response to erythropoietin in the presence of infection or malignancy. Erythropoiesis 1992;3:29-30.  Back to cited text no. 3    
4.Muirhead N, Hodsman AB. Occult infection and resistance of anaemia to rHuEPO therapy in renalfailue. Nephrol Dial Transplant 1990;5:232-4.  Back to cited text no. 4  [PUBMED]  
5.Rao DS, Shih MS, Mohini R. Effect of serum parathyroid hormone and bone marrow fibrosis on the reponse to erythropoietin in uremia. N Engl J Med 1993;328:171-5.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Macdougall IC. Poor response to erythropoietin. Br Med J 1995;310:142-5.  Back to cited text no. 6    
7.Ifudu O, Feldman J, Friedman EA. The intensity of hemodialysis and the response toerythropoietin in patients with end-stage renal disease. N Engl J Med 1996;334:420-­5.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Escbach JW, Adamson JW, Recombinant human erythropoietin: implications for nephrology. Am J Kidney Dis 1998;11:203­-9.  Back to cited text no. 8    
9.Sunder-Plassmann G, Horl WH. Importance of iron supply for erythropoietin therapy. Nephrol Dial Transplant 1995;10:2080-6.  Back to cited text no. 9    
10.Eschbach JW, Abdullhadi MH, Browne JK, et al. Recombinant human ertythropoietin in anemic patients with end-stage renal disease: results of a phase III multicenter clinical trial. Ann Intern Med 1989;111:992-1000.  Back to cited text no. 10    
11.Macdougall IC, Hutton RD, Cavill I, Coles GA, Williams JD, Poor response to treatment of renal anaemia with erythropoietin corrected by iron given intravenously. Br Med J 1989;229:157-8.  Back to cited text no. 11    
12.Allegra V, Mangozzi G, Vasile A. Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments. Nephron 1991;57:175-82.  Back to cited text no. 12    
13.Van Wyck DB, Stivelman JC, Ruiz J, Kirlin LF, Katz MA, Ogden DA. Iron status in patients receiving erythropoietin status in patients receiving erythropoietin for dialysis-associated aneima. Kidney Int 1989;35:712-6.  Back to cited text no. 13  [PUBMED]  
14.Muirhead N, Bargman J, Burgess E, et al. Evidence-based recommendations for the clinical use of recombinant human erythropoietin. Am J Kidney Dis 1995;26:S1024.  Back to cited text no. 14    
15.Golubov J, Flanagan P, Adams P. Inhibitiion of iron absorption by omeprazole in rat model. Dig Dis Sci 1991;36:405-8.  Back to cited text no. 15  [PUBMED]  
16.Grebe G, Martinez-Torres C, Layrisse M. Effect of meals and ascorbic acid on th absorption of a therapeutic dose of iron as ferrous and ferric salts. Curr ther Res clin Esp 1975;17:382-97.  Back to cited text no. 16    
17.MacDougall IC, tucker B, Thompson J, Baker LRI, Raine AEG. A randomized controlled study of iron supplementation in patients treated with erythropoietin. J Am Soc Nephrol 1993;4:428(abstract).  Back to cited text no. 17    
18.Sunder-Plassman G, Horl WH. Importance of iron supply for erythropoietin therapy. Nephrol Dial Transplant 1995;10:2070-6.  Back to cited text no. 18    
19.Fishbane S, Frei GL, Maesaka J. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis 1995;26:41-6.  Back to cited text no. 19  [PUBMED]  
20.Hamstra RD, Block MH, Schocket AL. Intravenous iron dextran in clinical medicine. JAMA 1980;243:1726-31.  Back to cited text no. 20  [PUBMED]  
21.Fishbane S, Ungureanu VD, Maesaka JK, Keupke CJ, Lim V, Wish J. The safety of intravenous iron dextran in hemosialysis patients. Am J Kidney Dis 1996;28:529-34.  Back to cited text no. 21    

Correspondence Address:
Saleh Abu Romeh
Department of Medicine, King Fahad National Guard Hospital, P.O. Box 22490, Riyadh 11426
Saudi Arabia
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PMID: 18212409

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