© 1991 S. Karger AG, Basel 0028 -2766/91/0574-0485S2.75/0
Nephron 1991:57:485-486
Recombinant Human Erythropoietin in Anemic Patients on Maintenance Hemodialysis: Comparison between Intravenous and Subcutaneous Administration C. Zehnder, A. Blumberg Division of Nephrology, Department of Medicine, Kantonsspital Aarau, Switzerland
Recombinant human erythropoietin (r-huEPO) is now an established therapy for the anemia of hemodialy sis patients [1-3]. In a previous study [4], we compared the effectiveness of intravenous (i.v.) and subcutaneous (s.c.) r-huEPO in maintaining in 9 hemodialysis patients a stable hemoglobin level of 10-13 g/dl during two 3-month periods, s.c. r-huEPO twice weekly was found to be as effective at a lower dose as i.v. r-huEPO administred thrice weekly. In order to confirm these results over a longer period, the s.c. r-huEPO dosage necessary to maintain a target hemoglobin level of 10-13 g/dl was followed in 14 pa tients. For 3 months hemoglobin was kept at the target level with individually titrated i.v. r-huEPO administered thrice weekly after each hemodialysis. Patients were then switched to s.c. r-huEPO. Initially, approximately 50% of the previous weekly i.v. dose was given as twice weekly s.c. injections. The dosage was adapted to maintain the desirable hemoglobin concentration: with hemoglobin concentrations < 10 g/dl r-huEPO was increased every 2 weeks by a third of the weekly dose; with hemoglobin concentrations > 13 g/dl the dose was reduced by a third. Seven patients were followed during 9,4 during 6 and 3 during 3 months of s.c. r-huEPO administration. The last 3 patients did not complete the study, 2 because of severe anemia due to intercurrent operations (femoropopliteal bypass, reanastomosis of a colostomy and crea tion of a new a-v hemodialysis fistula) requiring an increase in r-huEPO not compatible with the s.c. route, and I because of a kidney transplant.
Table 1. r-huEPO doses: comparison between the last i.v. and s.c. doses after 3, 6 and 9 months Patient No.
i.v. r-huEl>0 U /kg/w et ;k
s.c. r-huEPO U/kg/week 3 months
6 months
9 months
69 43 111 154 67 51 42 59 90 208 96
69 43 111 204 67 72 42
1 2 3 4 5 6 7 8 9 10 II 12 13 14
92 90 200 225 150 336 218 III 167 195 216 286 442 278
68 43 110 117 72 154 73 59 86 132 96 156 230 280
Mean ± SD
215+98*
120 ±68
90 ±51
87 ±57
* p < 0.001 for difference i.v. versus s.c.
Table 1gives a comparison between the last individual i.v. and the s.c. r-huEPO doses after 3, 6 and 9 months. The hemoglobin levels of the patients are shown in table 2. The s.c. doses were increased in 3/14 patients at 3 months of treatment. One of these patients needed an other rise of the dose after 5 months. Patient No. 4 needed
Downloaded by: Glasgow Univ.Lib. 130.209.6.61 - 11/22/2017 11:00:57 AM
Dear Sir,
Zehnder/Blumberg
486
Patient No.
Hb. g/dl i.v. r-huEPO
s.c. r-huEPO 3 months
6 months
9 months
9.9 11.4 11.6 11.0 12.4 12.3 12.6 11.4 13.0 10.7 12.6
11.5 11.9 12.4 9.2 12.0 11.5 12.4
10.3 11.1 11.8 10.9 13.7 11.1
12 13 14
10.6 10.9 11.2 11.4 11.9 11.3 10.7 10.6 11.8 11.2 11.4 9.8 11.5 10.9
M ean±SD
11.1 ±0.6*
II.5 ±1.0
1
2 3 4 5 6 7 8 9 10 11
*
11.0
11.0
13.0 12.8 11.0
11.0
10.5 9.9 11.7 ± 1.1
11.4 ± 1.1
Not significant for difference i.v. versus s.c.
higher doses after 4, 6 and 8 months. In 11/14, 9/11 and 6/7 the doses remained stable or could even be reduced in some patients at 3, 6 and 9 months, respectively. In these latter patients s.c. doses amounted to (mean ± SD) 49 ±6, 45 ± 18 and 44 ±21% of the last i.v. doses. During the observation period no patient needed more s.c. then i.v. r-huEPO. Apart from small s.c. hematomas no local and general side effects were observed.
Subcutaneous administration of r-huEPO twice weekly is effective in the treatment of the anemia of hemodialysis patients. For each patient the optimal dose needs to be established by titration. In the present study the maintenance s.c. r-huEPO doses were between 42 and 280 U/kg/week. In comparison with the i.v. route s.c. administration is more economical, practical, safe and well accepted by hemodialysis patients.
References 1 Eschbach JW, Egrie JC, Downing MR. et al: Correction of the anemia of end stage renal disease with recombinant human erythropoietin. N Engl J Med 1987;316:73-78. 2 Winearls CG. Oliver DO, Pippard MJ. et al: Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986; ii: 1175-1177. 3 Zehnder C, Blumberg A: Human recombinant erythropoietin treatment in transfusion dependent anemic patients on mainte nance hemodialysis. Clin Nephrol 1989:31:55-59. 4 ZehnderC, Blumberg A: Behandlung der Anämie von Hämodi alysepatienten mit rekombinantem humanem Erythropoietin: Vergleich zwischen intravenöser und subkutaner Verabrei chung. Schweiz Med Wochenschr 1990:120:217-220.
Dr. C. Zehnder Division of Nephrology Department of Medicine Kantonsspital Aarau CH-5001 Aarau (Switzerland)
Downloaded by: Glasgow Univ.Lib. 130.209.6.61 - 11/22/2017 11:00:57 AM
Table 2. Hemoglobin levels during i.v. and s.c. r-huEPO admini stration
Nephron 1991:57:485-486
Recombinant Human Erythropoietin in Anemic Patients on Maintenance Hemodialysis: Comparison between Intravenous and Subcutaneous Administration C. Zehnder, A. Blumberg Division of Nephrology, Department of Medicine, Kantonsspital Aarau, Switzerland
Recombinant human erythropoietin (r-huEPO) is now an established therapy for the anemia of hemodialy sis patients [1-3]. In a previous study [4], we compared the effectiveness of intravenous (i.v.) and subcutaneous (s.c.) r-huEPO in maintaining in 9 hemodialysis patients a stable hemoglobin level of 10-13 g/dl during two 3-month periods, s.c. r-huEPO twice weekly was found to be as effective at a lower dose as i.v. r-huEPO administred thrice weekly. In order to confirm these results over a longer period, the s.c. r-huEPO dosage necessary to maintain a target hemoglobin level of 10-13 g/dl was followed in 14 pa tients. For 3 months hemoglobin was kept at the target level with individually titrated i.v. r-huEPO administered thrice weekly after each hemodialysis. Patients were then switched to s.c. r-huEPO. Initially, approximately 50% of the previous weekly i.v. dose was given as twice weekly s.c. injections. The dosage was adapted to maintain the desirable hemoglobin concentration: with hemoglobin concentrations < 10 g/dl r-huEPO was increased every 2 weeks by a third of the weekly dose; with hemoglobin concentrations > 13 g/dl the dose was reduced by a third. Seven patients were followed during 9,4 during 6 and 3 during 3 months of s.c. r-huEPO administration. The last 3 patients did not complete the study, 2 because of severe anemia due to intercurrent operations (femoropopliteal bypass, reanastomosis of a colostomy and crea tion of a new a-v hemodialysis fistula) requiring an increase in r-huEPO not compatible with the s.c. route, and I because of a kidney transplant.
Table 1. r-huEPO doses: comparison between the last i.v. and s.c. doses after 3, 6 and 9 months Patient No.
i.v. r-huEl>0 U /kg/w et ;k
s.c. r-huEPO U/kg/week 3 months
6 months
9 months
69 43 111 154 67 51 42 59 90 208 96
69 43 111 204 67 72 42
1 2 3 4 5 6 7 8 9 10 II 12 13 14
92 90 200 225 150 336 218 III 167 195 216 286 442 278
68 43 110 117 72 154 73 59 86 132 96 156 230 280
Mean ± SD
215+98*
120 ±68
90 ±51
87 ±57
* p < 0.001 for difference i.v. versus s.c.
Table 1gives a comparison between the last individual i.v. and the s.c. r-huEPO doses after 3, 6 and 9 months. The hemoglobin levels of the patients are shown in table 2. The s.c. doses were increased in 3/14 patients at 3 months of treatment. One of these patients needed an other rise of the dose after 5 months. Patient No. 4 needed
Downloaded by: Glasgow Univ.Lib. 130.209.6.61 - 11/22/2017 11:00:57 AM
Dear Sir,
Zehnder/Blumberg
486
Patient No.
Hb. g/dl i.v. r-huEPO
s.c. r-huEPO 3 months
6 months
9 months
9.9 11.4 11.6 11.0 12.4 12.3 12.6 11.4 13.0 10.7 12.6
11.5 11.9 12.4 9.2 12.0 11.5 12.4
10.3 11.1 11.8 10.9 13.7 11.1
12 13 14
10.6 10.9 11.2 11.4 11.9 11.3 10.7 10.6 11.8 11.2 11.4 9.8 11.5 10.9
M ean±SD
11.1 ±0.6*
II.5 ±1.0
1
2 3 4 5 6 7 8 9 10 11
*
11.0
11.0
13.0 12.8 11.0
11.0
10.5 9.9 11.7 ± 1.1
11.4 ± 1.1
Not significant for difference i.v. versus s.c.
higher doses after 4, 6 and 8 months. In 11/14, 9/11 and 6/7 the doses remained stable or could even be reduced in some patients at 3, 6 and 9 months, respectively. In these latter patients s.c. doses amounted to (mean ± SD) 49 ±6, 45 ± 18 and 44 ±21% of the last i.v. doses. During the observation period no patient needed more s.c. then i.v. r-huEPO. Apart from small s.c. hematomas no local and general side effects were observed.
Subcutaneous administration of r-huEPO twice weekly is effective in the treatment of the anemia of hemodialysis patients. For each patient the optimal dose needs to be established by titration. In the present study the maintenance s.c. r-huEPO doses were between 42 and 280 U/kg/week. In comparison with the i.v. route s.c. administration is more economical, practical, safe and well accepted by hemodialysis patients.
References 1 Eschbach JW, Egrie JC, Downing MR. et al: Correction of the anemia of end stage renal disease with recombinant human erythropoietin. N Engl J Med 1987;316:73-78. 2 Winearls CG. Oliver DO, Pippard MJ. et al: Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986; ii: 1175-1177. 3 Zehnder C, Blumberg A: Human recombinant erythropoietin treatment in transfusion dependent anemic patients on mainte nance hemodialysis. Clin Nephrol 1989:31:55-59. 4 ZehnderC, Blumberg A: Behandlung der Anämie von Hämodi alysepatienten mit rekombinantem humanem Erythropoietin: Vergleich zwischen intravenöser und subkutaner Verabrei chung. Schweiz Med Wochenschr 1990:120:217-220.
Dr. C. Zehnder Division of Nephrology Department of Medicine Kantonsspital Aarau CH-5001 Aarau (Switzerland)
Downloaded by: Glasgow Univ.Lib. 130.209.6.61 - 11/22/2017 11:00:57 AM
Table 2. Hemoglobin levels during i.v. and s.c. r-huEPO admini stration
