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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1995  |  Volume : 6  |  Issue : 4  |  Page : 407-411
Once Weekly Low Dose Subcutaneous Erythropoietin: An Economic Solution for the Management of Anemia of End-stage Renal Disease


Department of Nephrology, King Fahd Hospital, Madinah Al Munawarah, Saudi Arabia

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   Abstract 

Forty patients with end-stage renal disease on maintenance hemodialysis were categorized into three groups depending upon the route of administration of erythropoietin (EPO). Eighteen of these patients received i.v. EPO (group A), 11 were switched from i.v. to s.c. route (group B), and 11 other patients were started on s.c. EPO from the beginning of treatment (group C). They were studied to evaluate the efficacy of EPO and its dosage. The target hemoglobin was decided to be between 9 and 10.5 g/L. The hemogram of all these patients showed considerable improvement after EPO treatment. Mean hemoglobin level increased from 7.0 ± 1.0 in all the groups to 9.0 + 1.0, 9.1 ± 0.9 and 9.0 + 0.9 g/dl in groups A,B, and C respectively. Mean dose of EPO to achieve target hemoglobin was 120 ± 42.2, 42.6 + 16.2 and 36.6 + 11.1 U/Kg/week in groups A, B, and C respectively. Our observation illustrates that once weekly s.c. EPO is equally effective as i.v. EPO albeit at reduced dose and hence saving costs substantially without compromising patient care. Also, it maintains hemoglobin in target range in patients already stabilized on i.v. EPO.

Keywords: Hemodialysis, Anemia, Subcutaneous, Erythropoietin, Intravenous.

How to cite this article:
Bernieh B, Sirwal IA, Wafa A, Abbade MA, Ahmed M. Once Weekly Low Dose Subcutaneous Erythropoietin: An Economic Solution for the Management of Anemia of End-stage Renal Disease. Saudi J Kidney Dis Transpl 1995;6:407-11

How to cite this URL:
Bernieh B, Sirwal IA, Wafa A, Abbade MA, Ahmed M. Once Weekly Low Dose Subcutaneous Erythropoietin: An Economic Solution for the Management of Anemia of End-stage Renal Disease. Saudi J Kidney Dis Transpl [serial online] 1995 [cited 2020 Aug 12];6:407-11. Available from: http://www.sjkdt.org/text.asp?1995/6/4/407/40559

   Introduction Top


Erythropoietin (EPO) deficiency is consi­dered to be the major cause of anemia in patients with end-stage renal disease (ESRD) [1],[2] . Prior to the advent of recombinant, human EPO these patients were dependent on blood transfusion with its attendant risk of transmitting blood-borne infections, sensitization to HLA antigens and iron overload [3] . The efficacy of EPO in correcting anemia of chronic renal failure has been demonstrated in several studies [4],[5],[6],[7] . However, the drug is expensive and alternative methods are being sought to minimize the cost of treatment. The purpose of this study was to determine whether the hemoglobin level can be maintained within the acceptable range in patients on hemo­dialysis (HD) by once weekly subcutaneous (s.c.) administration of low dose EPO or on switching from the intravenous (i.v.) to the s.c. route in patients with already stabilized hemoglobin levels.


   Material and Methods Top


Forty patients with ESRD on maintenance HD were included in the study. They were divided into three groups: Group A (18 patients) receiving i.v. EPO three times per week, Group B (11 patients) switched from three times per week i.v. to once weekly s.c. EPO and Group C (11 patients) receiving s.c. EPO right from the beginning. The salient characteristics of these groups are shown in [Table - 1]. Patients who had evidence of blood loss, chronic infection, hemolysis or severe secondary hyperpara­thyroidism were excluded from the study. The dose of EPO was titrated to achieve a target hemoglobin of 9 to 10.5 g/dl. In group B, once the hemoglobin level was in the target range on i.v. EPO, the route of administration was changed to once weekly s.c. using one third of the i.v. dose. All patients with low serum ferritin levels received oral iron supplementation. The investigations that were carried out included: complete blood count, blood urea, serum creatinine, electrolytes, calcium and phosphates, liver function tests, serum iron and ferritin. The blood count was repeated twice monthly while the other investigations were performed once a month. All patients were carefully observed for side effects of EPO and the results were analyzed after six months of treatment.


   Dosage of Erythropoietin Top


Group A:

These patients were initially started on 50 U/kg three times per week administered i.v. at the end of each HD session. The dose was increased by 25 U/kg at four weekly intervals if an adequate response was not observed.

Group B:

Patients whose hemoglobin levels were stabilized on a certain i.v. dose of EPO, were switched on to s.c. administration using 1/3 the total weekly .i.v. dose.

Group C:

Patients were started initially on 50 U/kg once weekly s.c. EPO. The dose was sub­sequently titrated to achieve the target hemo­globin. Erythropoietin was administered at the end of the last dialysis session of the week.


   Results Top


The etiology of ESRD in the study patients is given in [Table - 2]. During treatment with EPO all the 40 patients in the three groups showed an increase in hemoglobin to the target level (9 to 10.5 g/dl) irrespective of age, sex and etiology of ESRD. The results are summarized in [Table - 3]. In some group B patients, there was an initial decrease in hemoglobin levels after switching over to s.c. administration. Subsequently, the target levels could be achieved. The mean dose of EPO in units/kg body weight/week required to achieve target hemoglobin was 120 ± 42.2 in group A, 42.6 ± 16.2 in group B and 36.6 + 11.1 in group C. The difference in the dose of EPO among groups A and C and groups A and B was statistically significant (P < 0.001) for achieving the same target hemoglobin [Figure - 1]. Blood transfusion requirements were reduced and all patients reported improvement in general well being. Three patients reported the disappearance of anginal attacks they were experiencing previously, after treatment with EPO was, initiated and correction of anemia was achieved. Erythropoietin was well tolerated by all patients. Three patients showed a rise in blood pressure to above normal levels. All the three were receiving i.v. EPO and were easily managed with anti-hypertensive medications. None of the patients from groups B and C developed or showed worsening of previously controlled hypertension. Two patients did not like the s.c. injection and complained of pain at the injection site. However, this did not necessitate changing the route of administration. None of the study patients had major EPO side effects like seizures, reduced dialysis efficiency, encephalopathy or clotting phenomenon. Thus, changing the route of administration of EPO from i.v. to s.c. permitted a reduction in the dose to 1/3 or 1/4 the earlier dose without compromising on the efficacy.


   Discussion Top


Erythropoietin improves anemia in majority of patients with ESRD [4] . Its efficacy in correcting anemia in patients on HD, continuous ambulatory peritoneal dialysis as well as pre-dialysis patients has been demonstrated in several studies [4],[5],[6],[7] . With the expanding use of EPO and the high cost involved, the major question is related to the most effective dose and route of administration. Also, the optimal hemo­globin level to aim for in these patients is as yet unclear. In our study, the target hemo­globin decided upon was lower than what is reported in other studies. However, we noticed that there was a good improvement in feeling of well being among our patients after achieving the target hemoglobin of 9 to 10.5 g/L suggesting that perhaps higher levels are not required.

Initial clinical trials used high doses of i.v. EPO to achieve the target hemoglobin [8],[9] . An even higher total dose was needed when EPO was administered once weekly [10] . Aswad, et al reported good results with a fixed i.v. dose of EPO (50 U/kg) thrice weekly in HD patients [11] . In a subsequent study, it was demonstrated that the dose of EPO could be reduced by 50% when the drug was given s.c. 2-3 times a week [12] . Pharmacokinetic and pharmacodynamic studies have shown that for a given target response, less EPO is required when the s.c. route is used [12] . The dose response to EPO is non-linear after either i.v. or s.c. administration. Also, the duration for which EPO levels are maintained, and not the absolute peak, is the primary determinant of efficacy [11] . The beneficial effect of s.c. EPO has led to switching of patients from the i.v. to the s.c. route of administration with good results [11],[13],[14] . Reduced dose requirements have been noted consistently while using the s.c. route either daily [15],[16] , 2-3 times per week [17] , twice weekly [18] or once a week [19],[20] . Horl analyzed a number of studies and found that s.c. administration could allow a dose reduction of about 50% [21] . In another study, reduction of the dose to 1/ 3 of the total weekly i.v. dose was demonstrated [19] .

The results of our study suggest that switching from the i.v. to the s.c. route or starting EPO s.c. from the beginning can maintain hemoglobin in the target range at 1/3 of the i.v. dose. It can lead to substantial cost saving without compromising the clinical efficacy.

 
   References Top

1.Adamson JW, Eschbach J, Finch CA. The kidney and erythropoiesis. Am J Med 1968;44:725-33.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Gurney CW, Jaoobson LO, Goldwasser E. The physiologic and clinical significance of erythropoietin. Ann Intern Med 1958;49:363-70.  Back to cited text no. 2    
3.Schafer Al, Cheron RG, Dluhy R, et al. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med 1981;319-24.  Back to cited text no. 3    
4.Eschbach JW, Adamson JW. Correction of anemia of hemodialysis patients with recombinant human erythropoietin: Result of a multicenter study. Kidney Int 1988;33:189(A).  Back to cited text no. 4    
5.Auer J, Simon G, Stevens J, et al. Quality of life improvements in CAPD patients treated with subcutaneously administered erythropoietin for anemia. Perit Dial Int 1992; 12:40-2.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Shaheen FAM, El-Aqeil N, Badawi L, et al. Correction of anemia by erythropoietin in predialysis patients. Saudi Kidney Dis Transplant Bull 1993;4(3):215-9.  Back to cited text no. 6    
7.Souqiyyeh MZ, Ojjeh A. Usage of recom­binant human erythropoietin (r-HuEPO) in predialysis patients. Saudi Kidney Dis Transplant Bull 1993;4(3): 231-3.  Back to cited text no. 7    
8.Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med 1987;316:73-8.  Back to cited text no. 8    
9.Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986;2:1175-8.  Back to cited text no. 9  [PUBMED]  
10.Bommer J, Alexiou C, Muller-Buhl U, Eifert J, Ritz E. Recombinant human erythropoietin therapy in haemodialysis patients - dose determination and clinical experience. Nephrol Dial Transplant 1987;2:238-42.  Back to cited text no. 10    
11.Aswad S, Rahman ARA, Moulana MAR, Babiker MAR, Huraib SO. Treatment of anemia of hemodialysis patients with small doses of erythro poietin. Saudi Kidney Dis Transplant Bull 1990;l(l):6-9.  Back to cited text no. 11    
12.Besarab A, Flaharty KK, Erslev AJ, et al. Clinical pharmacology and economics of recombinant human erythropoietin in end­stage renal disease: the case for subcutaneous administration. J Am Soc Nephrol 1992;2(9): 1405-16.  Back to cited text no. 12    
13.Besarab A, Vlasses P, Carol J, et al. Subcutaneous administration of recombinant human erythropoietin for treatment of ESRD anemia. Kidney Int 1990;37:236. Abstract.  Back to cited text no. 13    
14.Tomson CR, Feehally J, Walls J. Crossover comparison of intravenous and subcutaneous erythropoietin in haemodialysis patients. Nephrol Dial Transplant 1992;7:129-32.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Bommer J, Ritz E, Weinreich T, Bommer G, Ziegler T. Subcutaneous erythropoietin. Lancet 1988;2:406.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Bommer J, Barth HP, Zeier M, et al. Efficacy comparison of intravenous and subcutaneous recombinant human erythropoietin administration in hemodialysis patients. Contrib Nephrol 1991;88:136-43.  Back to cited text no. 16  [PUBMED]  
17.Shaheen FAM. Al Aqeil N, Badawi L, et al.Erythropoietin in hemodialysis patients: intravenous or subcutaneous. Saudi Kidney Dis transplant Bull 1993;4(l):13-7.  Back to cited text no. 17    
18.McMahon LP, Dawborn JK. Experience with low dose intravenous and sub­cutaneous administration of recombinant human erythropoietin. Am J Nephrol 1990;10:404-8.  Back to cited text no. 18  [PUBMED]  
19.Parker KP, Sands JM. "Weekly subcuta­neous erythropoietin maintains hematocrit in chronic hemodialysis patients. J Am Soc Nephrol 1993;3(10):1717-8.  Back to cited text no. 19    
20.Zappacosta AR. Weekly subcutaneous recombinant human erythropoietin corrects anemia of progressive renal failure. Am J Med 1991;91:229-32.  Back to cited text no. 20    
21.Horl WH. Optimal route of administration of erythropoietin in chronic renal failure patients: intravenous versus subcutaneous. Acta Haematol 1992;87 (Suppl l):16-9.  Back to cited text no. 21    

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Correspondence Address:
Bassam Bernieh
Nephrology Department, King Fahd Hospital, Madinah Al Munawarah
Saudi Arabia
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PMID: 18583749

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    Abstract
    Introduction
    Material and Methods
    Dosage of Erythr...
    Results
    Discussion
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