Pediatric Use of Recombinant Human Erythropoietin
Recombinant human erythropoietin (rHuEPO), also referred to as epoetin alfa, has Food and Drug Administration (FDA) approval for the treatment of anemia in pediatric patients with chronic renal failure (CRF) requiring dialysis. Literature is also available supporting its use in children with anemia associated with cancer chemotherapy, prematurity, or chronic illness. Recombinant human erythropoietin is generally well tolerated and may offer the benefit of reducing the need for blood transfusions in these pediatric populations. This article will review the use of rHuEPO in infants and children.
Erythropoietin is a glycoprotein which is essential in the production of red blood cells. It is produced in the kidney and stimulates the division and differentiation of erythroid progenitors in the bone marrow. Hypoxia and anemia increase the production of erythropoietin. Since rHuEPO is recombinant human erythropoietin, it has the same biological effects as endogenous erythropoietin.
There are many clinical studies describing the efficacy of rHuEPO in adult patients with anemia pre-dialysis, during hemodialysis (HD) or peritoneal dialysis (PD), and after transplant. The body of literature in pediatrics is smaller, but supportive. In 1994, Jabs and colleagues reported the results of a randomized, placebo-controlled, multicenter trial of rHuEPO in 113 HD (42%) and PD (58%) patients between 5 and 17 years of age. The initial rHuEPO dose was 50 units/kg three times weekly, intravenously (IV) for HD patients or subcutaneously (SC) for PD patients. At 12 weeks, the mean Hct had increased in the rHuEPO group (HD: 21% to 28%, PD: 23% to 34%) and remained unchanged in the placebo group. There were no significant differences between groups in adverse effects. Following the initial 12-week trial, all patients were given rHuEPO. After 24 weeks of rHuEPO, mean Hct was 31% in HD and PD patients. However, the average dose required in HD patients was significantly higher compared to PD patients (155 units/kg/week versus 91 units/kg/week). The dose in PD patients was significantly higher in children < 5 years old than in those 5-17 years old. Systolic and diastolic blood pressures significantly increased in HD patients, while only the diastolic blood pressure increased in PD patients. In addition, iron deficiency worsened during treatment.
A prospective, randomized study in 1999 by Brandt and colleagues evaluated the use of rHuEPO in 44 children (4 months to 21 years of age) with chronic renal disease. There were 25 pre-dialysis patients, 10 PD, and 9 HD patients. The children were randomized to either low-dose rHuEPO (150 units/kg/week) or high-dose (450 units/kg/week) divided three times weekly for 12 weeks or until an age-determined target hemoglobin (Hgb) was reached. Dose was then titrated to a normal Hgb. Hemodialysis patients received IV rHuEPO and children on PD or who were pre-dialysis received SC rHuEPO.
Eighty-two percent of patients achieved target Hgb at a mean of 7.9 weeks; 95% of patients in the high-dose group and 66% in the low-dose group reached target within 12 weeks. The overall median dose of rHuEPO required to maintain a normal Hgb was 150 units/kg per week. Although, there were no significant differences, HD patients tended to have higher dosage requirements (median 250 units/kg/week). The increase in Hgb was significant for all groups except the low-dose PD group. Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks, although there were no significant differences between groups. Hypertension occurred in 30% of patients and was significantly more common in HD patients (66%) than in PD (33%) or pre-dialysis (16%) patients. Iron deficiency was found in 30% of patients.
Recombinant human erythropoietin (rHuEPO), also referred to as epoetin alfa, has Food and Drug Administration (FDA) approval for the treatment of anemia in pediatric patients with chronic renal failure (CRF) requiring dialysis. Literature is also available supporting its use in children with anemia associated with cancer chemotherapy, prematurity, or chronic illness. Recombinant human erythropoietin is generally well tolerated and may offer the benefit of reducing the need for blood transfusions in these pediatric populations. This article will review the use of rHuEPO in infants and children.
Erythropoietin is a glycoprotein which is essential in the production of red blood cells. It is produced in the kidney and stimulates the division and differentiation of erythroid progenitors in the bone marrow. Hypoxia and anemia increase the production of erythropoietin. Since rHuEPO is recombinant human erythropoietin, it has the same biological effects as endogenous erythropoietin.
There are many clinical studies describing the efficacy of rHuEPO in adult patients with anemia pre-dialysis, during hemodialysis (HD) or peritoneal dialysis (PD), and after transplant. The body of literature in pediatrics is smaller, but supportive. In 1994, Jabs and colleagues reported the results of a randomized, placebo-controlled, multicenter trial of rHuEPO in 113 HD (42%) and PD (58%) patients between 5 and 17 years of age. The initial rHuEPO dose was 50 units/kg three times weekly, intravenously (IV) for HD patients or subcutaneously (SC) for PD patients. At 12 weeks, the mean Hct had increased in the rHuEPO group (HD: 21% to 28%, PD: 23% to 34%) and remained unchanged in the placebo group. There were no significant differences between groups in adverse effects. Following the initial 12-week trial, all patients were given rHuEPO. After 24 weeks of rHuEPO, mean Hct was 31% in HD and PD patients. However, the average dose required in HD patients was significantly higher compared to PD patients (155 units/kg/week versus 91 units/kg/week). The dose in PD patients was significantly higher in children < 5 years old than in those 5-17 years old. Systolic and diastolic blood pressures significantly increased in HD patients, while only the diastolic blood pressure increased in PD patients. In addition, iron deficiency worsened during treatment.
A prospective, randomized study in 1999 by Brandt and colleagues evaluated the use of rHuEPO in 44 children (4 months to 21 years of age) with chronic renal disease. There were 25 pre-dialysis patients, 10 PD, and 9 HD patients. The children were randomized to either low-dose rHuEPO (150 units/kg/week) or high-dose (450 units/kg/week) divided three times weekly for 12 weeks or until an age-determined target hemoglobin (Hgb) was reached. Dose was then titrated to a normal Hgb. Hemodialysis patients received IV rHuEPO and children on PD or who were pre-dialysis received SC rHuEPO.
Eighty-two percent of patients achieved target Hgb at a mean of 7.9 weeks; 95% of patients in the high-dose group and 66% in the low-dose group reached target within 12 weeks. The overall median dose of rHuEPO required to maintain a normal Hgb was 150 units/kg per week. Although, there were no significant differences, HD patients tended to have higher dosage requirements (median 250 units/kg/week). The increase in Hgb was significant for all groups except the low-dose PD group. Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks, although there were no significant differences between groups. Hypertension occurred in 30% of patients and was significantly more common in HD patients (66%) than in PD (33%) or pre-dialysis (16%) patients. Iron deficiency was found in 30% of patients.