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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1994  |  Volume : 5  |  Issue : 2  |  Page : 168-172
Intravenous Iron Saccharate in Hemodialysis Patients Receiving r-HuEPO


1 College of Medicine and King Khalid University Hospital, Riyadh, Saudi Arabia
2 King Fahd National Guard Hospital, Riyadh, Saudi Arabia

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   Abstract 

A study was undertaken to evaluate the safety and efficacy of iron saccharate in regular haemodialysis (HD) patients receiving r-HuEPO. A total of 109 patients (57 males, 52 females, mean age 34.1 + 11.7 years) were included in the study, 64 of whom were iron deficient. The patients were divided into two groups. Group I (n = 58) received high dose iron saccharate (500 mg), intravenously (i.v.) (1-2 doses), and Group II (n = 51) received low dose iron saccharate (100 mg), i.v., thrice per week (5-10 doses). Results at four weeks showed a significant increment in hemoglobin (Hb), hematocrit (Hct), and serum ferritin in both groups. Two patients developed headache, fever and urticaria, and three patients developed fever in group I. None of the patients in group II developed any adverse reaction. Intravenous iron supplementation with iron saccharate in HD patients showing poor response to r-HuEPO, produced satisfactory Hct levels without major side effects and without the need to increase the dose of r-HuEPO. Commonly observed side effects were not seen with the low dose regimen.

Keywords: Iron saccharate, Iron deficiency, Haemodialysis, Erythropoietin, r-HuEPO, Functional iron deficiency.

How to cite this article:
Al-Momen AKM, Huraib SO, Mitwalli AH, Al-Wakeel J, Al-Yamani MJ, Abu-Aisha H, Said R. Intravenous Iron Saccharate in Hemodialysis Patients Receiving r-HuEPO. Saudi J Kidney Dis Transpl 1994;5:168-72

How to cite this URL:
Al-Momen AKM, Huraib SO, Mitwalli AH, Al-Wakeel J, Al-Yamani MJ, Abu-Aisha H, Said R. Intravenous Iron Saccharate in Hemodialysis Patients Receiving r-HuEPO. Saudi J Kidney Dis Transpl [serial online] 1994 [cited 2020 Jul 5];5:168-72. Available from: http://www.sjkdt.org/text.asp?1994/5/2/168/41344

   Introduction Top


Iron deficiency contributes significantly to anemia in haemodialysis patients mainly because of blood loss [1],[2],[3],[4] and inadequate iron supplement. Reasons for recurrent blood loss in haemodialysis patients include uremia-associated bleeding tendency due to blood vessel and platelet dysfunctions [5],[6],[7] uremia-the related gastrointestinal abnor­malities such as telangiectasia and hemor­rhage [8],[9] , loss during dialysis [10],[11],[12],[13] and iatrogenic (by excessive, repeated blood sampling) [14] . In uremic patients, oral intake of iron is often inadequate due to factors such as poor consumption of iron containing foods, side effects of oral iron preparations leading to non-compliance and finally, iron malabsorption associated with use of antacids given for phosphate binding [15],[16],[17] . Since recombinant human erythro­poietin (r-HuEPO) became available for use in haemodialysis patients, blood transfusion, with its related iron overload and other adverse effects, is much less commonly undertaken [3],[4],[18],[19] . In order to induce erythropoiesis, r-HuEPO requires adequate iron supplement. Without adequate iron supplement, erythropoiesis becomes blunted, leading to unresponsiveness to rHuEPO which improves only with adequate iron therapy [20],[21],[22],[23],[24],[25] . Routes of iron administra­tion include oral, intramuscular, or intra­venous. Oral iron administration to haemodialysis patients with iron deficiency is often insufficient, inconvenient, and usually results in delayed response and non­compliance [16],[17],[20],[26] . Intramuscular injections are relatively contraindicated in patients on haemodialysis because of the associated bleeding tendency. Besides, intramuscular administration of iron prepa­rations may be associated with local malignancy [28],[29],[30],[31] . There are two forms of intravenous iron preparations generally available. First, iron dextran which is widely used [20],[26],[32],[33] . However, up to 30% of patients develop side effects which include anaphylaxis, urticaria, fever, headache, nausea, vomiting, severe arthralgia and meningism [16],[34],[35],[36],[37],[38] . The second preparation is iron saccharate which has minimal side effects and, has been successfully used in haemodialysis patients, pregnant women and other conditions with iron deficiency [39],[40],[41] . In this study we present our experience with intravenous iron saccharate (Ferosac®, SPIMACO, Saudi Arabia) in haemodialysis patients comparing two dosage forms, (i) high dose = 500 mg, once weekly (one to two doses) and (ii) low dose = 100 mg, thrice weekly (five to ten doses).


   Patients and Methods Top


Adult regular haemodialysis patients were selected from the haemodialysis units at King Khalid University Hospital, Security Forces Hospital and King Fahad National Guard Hospital. There were 109 patients, 57 males and 52 females, aged 17-65 (mean 34.1 ± 11.7) years. All patients were on treatment with r-HuEPO (EPREX, Cilag AG International, Switzerland) for a minimum period of eight weeks. Patients who were iron deficient (ID), (n = 64), were given r-HuEPO up to 100 units/kg thrice weekly for at least eight weeks. Patients who were not iron deficient (NID) (n = 45), were given r-HuEPO 50 units/ kg i.v. thrice/week for at least 8 weeks. In both ID and NID patients Hct levels remained below the target value of 35% [Table 1]. Each patient underwent a meticulous medical evaluation to rule out causes of anemia other than renal failure and/or iron deficiency. Initial laboratory work-up included complete blood count, blood urea nitrogen (BUN), creatinine, electrolytes, liver functions, serum iron (Fe), total iron binding capacity (TIBC), ferritin, vitamin Bi2, serum and RBC folate, and serology for inflammatory disorders. Patients were excluded from the study if they had active bleeding, haemo­lysis, inflammation, infection, malignancy, or if they had any contraindication. Patients were divided into two main groups. Group I received a high dose iron saccharate, 500 mg in 250 cc normal saline, i.v., over 1-4 hours once, to be repeated at weekly inter­vals up to the total dose which was calculated as Hb difference (target Hb minus current Hb) x body weight (kg) x 3 in those who have iron deficiency. Group II received low, fractionated dose of 100 mg in 25 cc normal saline, i.v., over 5-10 min, thrice weekly for 5 to 10 doses. Vital signs and possible side effects such as anaphylaxis, urticaria, fever, headache, nausea, vomiting, severe arthralgia and meningism were monitored closely. The following blood tests were carried out at weekly intervals (while on treatment): complete blood count, serum iron, TIBC and ferritin.

Laboratory Tests

Hematologic parameters were obtained by using a Coulter S-Plus electronic blood counter (Coulter Electronics, USA), serum iron and iron binding capacity (TIBC) using Synchron CX system (Beckman Instruments, Inc, USA) and serum ferritin was estimated by ELISA technique using Enzymum-Test Ferritin (Boehringer Manheim GmbH Diagnostics, Germany).

Statistical Analysis

Paired Student's test was used to compare hematological and iron parameters before and four weeks after initiation of iron saccharate therapy.


   Results Top


The results are shown in [Table 1]. Group I (n = 58) consisted of 42 iron deficient and 16 non-iron deficient patients. Group II (n = 51) consisted of 22 iron deficient and 29 non-iron deficient patients. All patients from both groups showed a significant rise in their hemoglobin, hematocrit and serum ferritin at the fourth week of initiation of iron saccharate administration, although the NID patients were receiving only smaller dose of r-HuEPO (50 units/kg). In addition, ID patients from both groups showed a significant increase in MCV and MCH. The dose of r-HuEPO in ID patients also could be brought down to about 50 units/kg to sustain Hct at the target level.

Side Effects

Two patients in Group I developed fever, headache, nausea, hypotension, and urticaria after the completion of the iron saccharate infusion. They responded to treatment with antihistamines and hydrocortisone and the reaction disappeared in a few hours. Three patients developed headache, nausea, and skin discomfort after 2 hours during the infusion. The symptoms disappeared when the infusion was stopped and no specific treatment was needed. Four of the patients who developed reactions previously received smaller doses subsequently (i.e., 100 mg, similar to Group II) without any further adverse reactions. Group II patients did not show any adverse reactions.


   Discussion Top


This study clearly indicates the usefulness of parenteral iron supplement in haemodialysis patients for obtaining rapid response of Hct while on treatment with r-HuEPO. In most of these cases, especially those who are iron deficient, oral supplement is generally inadequate [15],[16],[17] , inconvenient, and may only produce a very slow response. Besides, with adequate iron supplement, smaller doses of rHuEPO produce optimal and rapid response. Our results are in agreement with many other studies [20],[21],[22],[23],[24],[25] . Intra­venous iron dextran has been widely used for iron supplement, but many physicians are reluctant to use it because of its serious adverse effects [16],[34],[35],[36],[37],[38] .

Our study differs from other studies in three ways. First, we used iron saccharate instead of iron dextran, with clear evidence of safety and lack of serious side effects. Second, we compared high dose (500 mg) and low dose (100 mg) and found that the patients receiving low doses did not have any side effect and even those who previously had adverse reactions to the high dose regime did not have further side effects when they were changed to the low dose regime. Third, patients required a smaller dose of r-HuEPO when they received iron supplements.

It is important to understand that cases with functional iron deficiency do exist, even in patients with apparently normal or high iron parameters such as serum ferritin and iron, since these parameters are not always reliable [43],[44],[45] . Therefore, one has always to monitor the more reliable predictors of iron deficiency such as transferrin satu­ration (iron/TIBC x 100), MCV and MCH. The earliest indication for iron deficiency would be low transferrin saturation (<20%) followed by reduced MCV and MCH even in the presence of normal or elevated ferritin [43],[44],[45] . Occasionally, bone marrow aspiration for evalution of iron stores is indicated [46],[47],[48],[49] . In our study, patients with functional iron deficiency were excluded.

We conclude that (a) intravenous iron supplementation with iron saccharate produces prompt hematocrit response in patients receiving r-HuEPO therapy and showing poor response and that iron saccharate is a safe, effective and convenient intravenous iron formulation for haemodialysis patients especially for those who receive r-HuEPO therapy even if they are not iron deficient, (b) patients who receive iron supplement require smaller doses of r­HuEPO and, (c) use of iron saccharate in small frequent doses is associated with fewer side effects.


   Acknowledgements Top


The authors would like to thank Ms Karima Saleh for collection of data, Mr Amir S. Marzouk for statistical analysis and Ms Vergie Vicente for secretarial assistance.

 
   References Top

1.Erslev AJ, Caro J. Anemia of chronic renal failure. In: Williams WJ, Beutler E, Erslev AJ, Liohtman MA (eds). Hematology. (4th edn.) New York: McGraw Hill, 1990:438-44.   Back to cited text no. 1    
2.Gutmann FD, Schwartz JC. Pathogenesis of anemia secondary to chronic renal failure. In: Garnick MB (ed). Erythropoietin in Clinical Applications. An International Perspective. New York: Marcel Dekker, 1990:105-40.  Back to cited text no. 2    
3.Eschbach JW, Cook JD, Scribner BH, Finch CA. Iron balance in haemodialysis patients. Ann Intern Med 1977;87:710-3.   Back to cited text no. 3  [PUBMED]  
4.Gokal R, Millard PR, Weatherall DJ, Callender ST, Ledingham JG, Oliver DO. Iron metabolism in hemodialysis. Q J Med 1979;48:369-91.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Castaldi PA, Rozenberg MC, Stewart JH. The bleeding disorder of uremia. A qualitative platelet defect. Lancet 1966;2:66-9.   Back to cited text no. 5    
6.Deykin D. Uremic bleeding. Kidney Int 1983;24:698-705.  Back to cited text no. 6  [PUBMED]  
7.Lewis JH, Zucker MB, Ferguson JH. Bleeding tendency in uremia. Blood 1956; 11:1073-6.  Back to cited text no. 7    
8.Mason EE. Gastrointestinal lesions occuring in uremia. Ann Intern Med 1952;37:96-105.  Back to cited text no. 8  [PUBMED]  
9.Dave PB, Romeu J, Antonelli A, Eiser AR. Gastrointestinal telangiectasias. A source of bleeding in patients receiving hemodialysis. Arch Int Med 1984;144:1781-3.   Back to cited text no. 9    
10.Koch KM, Patyna WD, Shaldon S, Werner E. Anemia of the regular haemodialysis patient and its treatment. Nephron 1974; 12:405-19.  Back to cited text no. 10  [PUBMED]  
11.Higgins MR, Grace M, Ulan RA, Silverberg DS, Bettcher KB, Dossetor JB. Anemia in haemodialysis patients. Arch Intern Med 1977;137:172-6.  Back to cited text no. 11  [PUBMED]  
12.Lindsay RM, Burton JA. Blood loss from cannula-tion sites during haemodialysis. Scott Med J 1972;17:266-9.  Back to cited text no. 12  [PUBMED]  
13.Lindsay RM, Kennedy AC. Dialysis and blood loss in regular dialysis therapy. Proc Eur Dial Transplant Assoc 1972;9:437-54.  Back to cited text no. 13  [PUBMED]  
14.Hocken AG, Marwah PK. Iatrogenic contribution to anaemia of chronic renal failure. Lancet 1971;l:164-5.  Back to cited text no. 14    
15.Fairbanks VF, Beutler E. Iron metabolism. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA (eds). Hematology, (4th edn). New York: McGraw Hill, 1990;329-39.   Back to cited text no. 15    
16.Fairbanks VF, Beutler E. Iron deficiency. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA (eds) Hematology, (4th edn). New York McGraw Hill, 1990;482-505.  Back to cited text no. 16    
17.Donnelly SM, Posen GA, AH MA. Oral iron absorption in haemodialysis patients treated ith erythropoietin. Clin Invest Med 1991;14:271-6.  Back to cited text no. 17    
18.Adamson JW. Iron and erythropoiesis. In: Bauer C, Koch KM, Scigalla P, Wieczorek L, (eds). Erythropoietin. Molecular Physiology and Clinical Applications. New York: Marcel Dekker, 1993:161-75.  Back to cited text no. 18    
19.Merrill RH. Iron metabolism in end stage renal disease. Dial Transplant 1979;8:898-904.  Back to cited text no. 19    
20.Skikne BS, Cook JD, Influence of recombinant human erythropoietin on iron metabolism in healthy subjects. In: Bauer C, Koch KM, Scigalla P, Wieczorek L (eds). Erythropoietin. Molecular Physiology and Clinical Application. New York: Marcel Dekker, 1993;177-87.  Back to cited text no. 20    
21.Horl WH, Dreyling K, Steinhauer HB, Engelhardt R, Schollmeyer P. Iron status of dialysis patients under r-HuEPO therapy. Contrib Nephrol 1990;87:78-86.   Back to cited text no. 21    
22.Granolleras C, Oules R, Branger B, Fourcade J, Shaldon S.. Iron supplementation of haemodialysis patients receiving recombinant human erythropoietin therapy. In: Bauer C, Koch KM, Scigalla P, Wieczorek L (eds).Erythropoietin. Molecular Physiology and Clinical Applications. New York:Marcel Dekker, 1993:211-6.  Back to cited text no. 22    
23.Cavill I, Macdougall IC. Erythropoiesis and iron supply in patients treated with erythropoietin. Erythropoiesis: New dimensions in the treatment of anaemia, 1992;3:50-5.   Back to cited text no. 23    
24.Van Wyck DB. Iron deficiency in patients with dialysis-associated anemia during erythropoietin replacement therapy: strategies for assessment and management. Semin Nephrol 1989;9(Suppl2):21:4.   Back to cited text no. 24    
25.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;299:157-8.  Back to cited text no. 25    
26.Danielson BG. EPO and the treatment of renal anaemia: Introduction. In: Overview of the Literature Related to Erythropoietin. Amsterdam Ex-cerpta Medica 1993;4:5-9.   Back to cited text no. 26    
27.Hotta T, Ogawa H, Saito A, Ito A. Iron balance following recombinant human erythropoietin therapy for anemia associted with chronic renal failure. Int J Hematol 1991;54:195-200.  Back to cited text no. 27  [PUBMED]  
28.Greenberg G. Sarcoma after intramuscular iron injection. Br Med J 1976;1:1508-9.  Back to cited text no. 28  [PUBMED]  [FULLTEXT]
29.MacKinnon AE, Bancewicz J. Sarcoma after injection of intramuscular iron. Br Med J 1973;2:277-9.  Back to cited text no. 29  [PUBMED]  [FULLTEXT]
30.Robinson CE, Bell DN, Sturdy JH. Possible association of malignant neoplasm with iron- dextran injection: a case report. Br med J 1960;2:648-50.  Back to cited text no. 30  [PUBMED]  [FULLTEXT]
31.Robertson AG, Dick WC. Intramuscular iron and local oncogenesis. Br Med J 1977;1:946.  Back to cited text no. 31    
32.Macdougall IC, Davies ME, Hutton RD, et al. The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin. Nephrol Dial Transplant 1990;5:950-5.  Back to cited text no. 32  [PUBMED]  
33.Steven ME, Summerfield GP, Hall AA, et al. Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease. Br Med J 1992;304:474-7.   Back to cited text no. 33    
34.Kumpf VJ, Holland EG. Parenteral iron dextran therapy. DICP 1990;24:162-6.   Back to cited text no. 34  [PUBMED]  
35.Bhatt RV, Joshi SK, Shah MC. Total dose intravenous infusion of iron-dextran (imferon) in severe anemia. Am J Obstet Gynecol 1966;94:1098-102.  Back to cited text no. 35  [PUBMED]  
36.Auerbach M, Witt D, Toler W, Fierstein M, Lerner RG, Ballard H. Clinical use of the total dose intravenous infusion of iron dextran. J Lab Clin Med 1988;111:566-70.   Back to cited text no. 36  [PUBMED]  
37.Johnson CS. Intravenous iron dextran in the treatment of iron deficient anemia. J Natl Med Assoc 1979;71:1101-5.  Back to cited text no. 37  [PUBMED]  
38.Hanson DB. Hendeles L. Guide to total dose intravenous iron dextran therapy. Am J Hosp harm 1974;31:592-5.   Back to cited text no. 38    
39.Kaltwasser JP, Werner E, Niechzial M. Bioavail- ability and therapeutic efficacy of bivalent and trivalent iron preparations. Arzneimittelforschung 1987;37:122-9.   Back to cited text no. 39  [PUBMED]  
40.Mackintosh W, Jacobs P. Response in serum ferritin and hemoglobin to iron therapy in blood donors. Am J Hematol 1988;27:17-9.   Back to cited text no. 40  [PUBMED]  
41.Sogbanmu MO. Anemia of pregnancy treated with total-dose infusion of iron polymaltose complex, Teferrol. Curr Ther Res Clin Exp 1976;20:149-55.   Back to cited text no. 41  [PUBMED]  
42.Dresch C, Boulard M, Najean Y. Comparison of the metabolism of 2 injectable iron preparations (sorbitol iron and polymaltose iron) with the metabolism of transferrin and hemoglobin iron. Nouv Rev Fr Hematol 1976;16:47-65.  Back to cited text no. 42  [PUBMED]  
43.Kaltwasser JP. Disturbances of iron metabolism in the anemia of chronic disorders. In:Bauer C, Koch KM, Scigalla P, Wieczorek L (eds). Erythropoietin. Molecular Physiology and Clinical Applications. New York: Marcel Dekker, 1993;189-206.  Back to cited text no. 43    
44.Mcdougall IC, Cavill I, Hulme B, et al. Detection of functional iron deficiency during erythropoietin treatment: a new approach. Br Med J 1992;304:225-6.  Back to cited text no. 44    
45.Nuwayri-Salti N, Jabre F, Daouk M, Sa'ab G, Salem Z. Hematologic parameters and iron stores in patients on hemodialysis for chronic renal failure. Clin Nephrol 1992;38:101-4.   Back to cited text no. 45  [PUBMED]  
46.Van Wijck DB. Iron management during recombinant human erythropoietin therapy. Am J Kidney Dis 1989;14(Suppl 1):9-13.  Back to cited text no. 46    
47.Bell JD, Kincaid WR, Morgan RG, et al. Serum ferritin assay and bone-marrow iron stores in patients on maintenance hemodialysis. Kidney Int 1980;17:237-41.  Back to cited text no. 47  [PUBMED]  
48.Ali M, Rigolosi R, Fayemi AO, Braun EV, Frascino J, Singer R. Failure of serum ferritin levels to predict bone-marrow iron content after intravenous iron-dextran therapy. Lancet 1982;l:652-5.  Back to cited text no. 48    
49.Moreb J, Popovtzer MM, Friedlaender MM, Konijn AM, Hershko C. Evaluation of iron status in patients on chronic hemodialysis. Relative usefulness of bone marrow hemosiderin, serum ferritin, transferrin saturation, mean corpuscular volume and red cell protoporphyrin. Nephron 1983;35:196-200.  Back to cited text no. 49    

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Correspondence Address:
Abdul-Kareem M Al-Momen
College of Medicine, King Khalid University Hospital, P.O. Box 2925, Riyadh 11461
Saudi Arabia
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