Pediatr Nephrol (1990) 4:618-622 9 IPNA 1990 Pediatric Nephrology Original article Recombinant human erythropoietin therapy in children maintained by haemodialysis Susan P. A. Rigden l, Giovanni Montini 1, Max Morris 1, Kenneth G. A. Clark 2, George B. Haycock 1, Cyril Chantlerl, and Ronald C. HilP I Department of Paediatrics, Evelina Children's Hospital and 2 Department of Haematology,Guy's Hospital, London SE1 9RT, UK 3 Medical Department, Cilag Ltd, Saunderton, High Wycombe,Bucks, UK Received October 17, 1989; received after revision April 6; accepted April 10, 1990 Abstract. Six children (aged 3 years 11 months to 15 years 9 months) with end-stage renal failure and anaemia (mean haemoglobin 7.1 g/dl, range 6.3-7.7 g/dl) on thrice- weekly haemodialysis were treated with recombinant human erythropoietin (rHuEPO), given as an intravenous bolus in an escalating dose regime after dialysis. All re- sponded with an increase in reticulocyte count and haemoglobin concentration in a mean time of 11 weeks (range 9-13 weeks) and at a dose of 100 or 150 units/kg thrice weekly. The dose of rHuEPO was then adjusted to maintain the haemoglobin concentration within the lower half of the normal range for the child's age and sex. The mean haemoglobin after 12 weeks treatment was 10.9 g/dl (range 8.5-12.1 g/dl) and after 24 weeks, 10.5 g/dl (range 7.9-13.3 g/dl). Four children had no further need for blood transfusion and are thus no longer at risk of blood-borne infection, iron overload and serfsitisation to HLA his- tocompatibility antigens. Serum ferritin fell in the three patients with evidence of iron overload; the three with low or normal iron stores at the onset of treatment maintained erythropoiesis with oral iron supplementation. HLA anti- bodies decreased in all patients. The only serious compli- cation encountered was thrombosis of vascular access in one child. No child became seriously hypertensive or developed cerebral symptoms. The benefits of rHuEPO therapy for children with end-stage renal failure are poten- tially considerable and with careful monitoring, the risks low. Key words: Recombinant human erythropoietin - End-stage renal failure - Haemodialysis - Anaemia - Iron overload - HLA antibodies Offprint requests to: S. R A. Rigden, 9th Floor Guy's Tower, Guy's Hospital, St. Thomas' Street, London SE1 9RT, UK Introduction Anaemia is a major debilitating complication of end-stage renal disease. The pathophysiology of this anaemia is com- plex and may include shortened red-cell survival, inhibi- tion of erythropoiesis by uraemic toxins, aluminium toxic- ity, iron and folate deficiency and blood loss on dialysis [1]. However the most important factor appears to be in- adequate production of erythropoietin [2], and human erythropoietin derived from recombinant DNA (rHuEPO) has now been used in clinical trials to correct the anaemia of adult patients with end-stage renal failure maintained by chronic haemodialysis [3, 4]. Children with end-stage renal disease tend to be more anaemic than adult patients, and are more likely to be transfusion dependent [5] with the attendant risks of blood- borne infection, iron overload and sensitisation to HLA antigens [6], which may reduce the chance of subsequent successful renal transplantation. This study was designed to assess the efficacy and safety of rHuEPO therapy in children with end-stage renal failure maintained on chronic haemodialysis. Patients and methods Six children with end-stage renal failure were studied; all were clinically stable and had been maintained by thrice weekly hospital haemodialysis for at least 3 months. Signed informed consent was obtained from their parents and, if appropriate, from the children. The study was approved by the hospital ethical committee.Patient details are snmmarisedin Table i. No child had any other cause for anaemia, any systemic disease that might mask a response to rHuEPO, uncontrolled hypertension, severe secondary hyperparathyroidism, evidence of aluminium toxicity, liver dysfunction, hepatitis B or human immunodeficiency virus infection. Pregnancy was excluded in the post-pubertal female patient. The trial was designed as an open-label non-randomised study with an escalating dose regime. After a 2-week placebo period during which only the diluent was given and base line data were collected, rHuEPO was commenced in a dose of 10 units/kg thrice weekly, given as an intravenous bolus at the end of dialysis. The children were admitted for 24 h following administration of the first dose for monitoring of vital signs (temperature, blood pressure, pulse and respiration rates). There-