Intraperitoneal administration of recombinant human erythropoietin in children on continuous ambulatory peritoneal dialysis

In 16 children treated by continuous ambulatory peritoneal dialysis (CAPD) recombinant human erythropoietin was administered intraperitoneally for the treatment of renal anaemia. The mean treatment period was 8.3 months. Mean haemoglobin values increased from 4.9 mmol/l at start of therapy to 6.2 after 6 months. While 11 out of 16 children needed a total of 22 transfusions during the 6 months prior to therapy, no transfusions were needed after initiation of therapy. Patients started with a dose of 300 units/kg per week. After 6 months of therapy, the mean dose was 370 and after 12 months 279 units/kg per week. No major side-effects were observed. The incidence of peritonitis was not increased. We conclude that intraperitoneal administration of erythropoietin is effective in the treatment of renal anaemia in children treated by CAPD.     

Deferoxamine for the treatment of hemosiderosis during CAPD

The effects of chelation therapy by intravenous and intraperitoneal administration of deferoxamine were compared during maintenance continuous ambulatory peritoneal dialysis (CAPD) in a child with end stage renal disease and hemosiderosis. We demonstrate that intraperitoneally administered deferoxamine is safer, more practical and efficient than weekly intravenously administered deferoxamine for the treatment of iron overload in the pediatric patient undergoing CAPD.     

Blood sampling in very low birth weight infants receiving different levels of intensive care

Sixty very low birth weight infants (birth weight 560–1450g) were studied during the first 28 days of life. The infants were classified as group A (n=19 infants who never required ventilator support), group B (n=20 infants mechanically ventilated for minor respiratory problems), and group C (n=21 infants ventilated for respiratory distress syndrome). Diagnostic blood sampling was measured, infants were checked for clinical symptoms and laboratory signs of anaemia 24 h before and after the transfusion of packed red cells. A total of 7998 punctures (average: 4.8 per infant per day) were performed, the mean blood loss due to diagnostic sampling was 50.3 ml/kg per 28 days (range 7–142) for all infants. A high correlation (r _s=+0.91) was found between the blood volumes sampled and transfused. In group A, the mean blood loss was 24 ml/kg, and a total of 29 blood transfusions were administered. The most frequent symptoms of anaemia were poor weight gain and apnoeic spells. In group B, the mean blood loss was 60 ml/kg and a total of 97 blood transfusions were administered. In group C, the mean blood loss was 67 ml/kg and a total of 116 blood transfusions were administered. In both groups B and C, poor weight gain, pallor and distended abdomen were the most frequent symtoms of anaemia. Following the blood transfusion, haematocrit rose and blood pressure remained unchanged. The symptoms that responded most favourably to the blood transfusion were: poor weight gain, oxygen requirement, and distended abdomen. The results emphasize the need for miniaturizing laboratory techniques and monitoring blood sampling.Abbreviations RDS respiratory distress syndrome - Hb haemoglobin     

Serum immunoreactive erythropoietin of children in health and disease

Serum immunoreactive erythropoietin (siEPO) was determined in cord serum from neonates (n=97, gestational age 36–43 weeks), in healthy children from birth to adolescence (n=260) and in children with haematological (n=30), renal (n=10) and congenital heart diseases (n=70). In healthy children siEPO levels decreased after birth (geometric mean cord siEPO 35.6 mU/ml with 95% range of 17–56 mU/ml in eutrophic, nondistressed fetuses) and reached lowest values during the first 2 months (geometric mean siEPO 11.5 mU/ml). Thereafter siEPO levels increased slightly and were constant between 2 months and adolescence. The geometric mean siEPO for healthy children after birth was 18.8 mU/ml with 95% range of 7–47 mU/ml. These estimates were not significantly different from normal adult values. In newborns with fetal distress (n=15) cord siEPO was significantly elevated (geometric mean 63.0 mU/ml;P<0.001). In children with haematological disease, siEPO and Hb concentration were inversely correlated (log siEPO (mU/ml)=4.1–0.20×Hb (g/dl);r=–0.62;P<0.0005). This relationship was significantly different in children with chronic renal failure (log siEPO (mU/ml)=0.67+0.035×Hb (g/dl);r=0.50;P=0.1). In children with heart disease the geometric mean siEPO was 19.2 mU/ml with 95% range 8–65 mU/ml for cyanotic (SaO₂<94%) and 17.7 mU/ml with 95% range of 12–36 mU/ml for acyanotic patients. In this group siEPO values were inversely correlated to the arterial oxygen content (log siEPO (mU/ml) =1.61–2.04×oxygen content (l/l);r=–0.28;P<0.02).     

Erythropoietin in children with chronic renal failure on dialytic and non-dialytic therapy

The serum values of erythropoietin and relationship with hemoglobin was studied in 29 children with chronic renal failure. 10 of the patients were receiving continuous ambulatory peritoneal dialysis (CAPD), 12 were on regular haemodialysis treatment (RHT) and 7 children were not on any form of dialysis treatment (ND). Serum erythropoietin was estimated using fetal mouse liver bioassay. The mean serum erythropoietin concentration in the three groups of patients were within the normal range but were inappropriately low for the degree of anemia (CAPD 19.6 +/- 8.0 mu/ml, RHT 25.7 +/- 13.2 mu/ml, ND 21.9 +/- 11.0 mu/ml. The haemoglobin value of (7.0 +/- 1.3 gm/dl) in the CAPD group was higher than in the RHT group (6.4 +/- 1.5 gm/dl), but this difference was not statistically significant (p greater than 0.1). In the non-dialysed patients, the mean haemoglobin value was 11.32 +/- 2.31 gm/dl and this was significantly higher than the values in the CAPD and RHT patients (p less than 0.05). No correlation was found between serum erythropoietin and haemoglobin in the three groups of patients.     

Preliminary Study of Autologous Blood Predonation in Pediatric Open-Heart Surgery

We applied an autologous blood predonation protocol using recombinant human erythropoietin in pediatric open-heart surgery. The study included 69 children weighing 8 kg or more. Twice before operation, 8 ml/kg of blood was taken. At each donation, 100 (group 1; n = 20), 200 (group 2; n = 11), or 300 (group 3; n = 13) units/kg of erythropoietin was given subcutaneously. In group 4 (n = 25), 300 units/kg of erythropoietin was given 1 week prior to the first donation, followed by 300 units/kg given at each donation. No harmful events occurred during the donation period. During the donation period, the patients hematocrit decreased but the hematocrit 1 day after the operation remained at 32.1 ± 0.6% and was 33.3 ± 0.6% 2 weeks later. The decrease in hematocrit was minimal in group 4 (39.0 ± 0.6% before donation to 37.5 ± 0.5% before operation) compared with that of the other three groups. Among those who completed the protocol, 58 patients (93.5%) were discharged without homologous blood transfusion. We consider our protocol of autologous blood predonation using erythropoietin to be safe and effective for avoiding homologous blood transfusion in pediatric patients. The early infusion of erythropoietin prior to the first donation minimizes the decrease in hematocrit level before operation.     

Endothelin concentrations in preterm infants treated with human recombinant erythropoietin

BACKGROUND: Increased endothelin-1 (ET-1) production following recombinant erythropoietin (Epo) administration is a presumed etiology for the hypertension reported in some adults. It is unknown whether Epo has similar effects in preterm infants. METHODS: Serum ET-1 and Epo concentrations were measured prior to study, and following the second and third doses in 20 preterm infants receiving intravenous (IV) or subcutaneous (SC) Epo. Blood pressures were monitored prior to Epo administration and during the first, second, and third dose. RESULTS: Infants (963 +/- 54 g birth weight, 27.4 +/- 0.6 weeks gestational age, 18 +/- 3 days of life; mean +/- SEM) had baseline Epo concentrations of 5.5 +/- 1.3 mU/ml and ET-1 concentrations below the lower limits of detection (<1 pg/ml). Epo concentrations were 1,848 +/- 274 and 1,672 +/- 295 mU/ml following the second and third IV dose, respectively, while Epo concentrations were 420 +/- 92 and 290 +/- 35 mU/ml after the second and third SC dose, respectively (p < 0.005, SC versus IV). ET-1 concentrations remained below the limits of detection in all but 6 infants, whose concentrations were <3.3 pg/ml. Blood pressures did not increase above baseline in either group during the study period. CONCLUSION: Despite the wide range of Epo concentrations measured, no correlation was observed between Epo concentrations, ET-1 concentrations, and blood pressure during the 1-week study period. The long-term effects of Epo on ET-1 concentrations and blood pressure in preterm infants require further study.     

Role of nitric oxide and cyclooxygenase pathway in lipopolysaccharide-induced intussusception

The etiology of intussusception (IN) remains largely obscure. In lipopolysaccharide (LPS)-induced IN, an experimental model in mice, IN is considered to be the consequence of altered intestinal motility as a result of increased nitric oxide (NO) along various inflammatory mediators. These could be decreased via cyclooxygenase (COX) inhibition by indomethacin. N--nitro-L-arginine methyl ester (L-NAME) inhibits nitric oxide synthase (NOS) and NO production. Indomethacin is known to prevent IN; however, the reason is unknown. In this study we aimed to determine the role of NO, the effects of inhibition of its production by L-NAME and indomethacin, and whether preventive effects of indomethacin on LPS-induced IN were related to NO inhibition. A total of 113 mice were divided into seven groups. In the control group (n=6), no procedure was done. In the sham group (n=6), 1 ml saline was given; in the indomethacin group (n=6), 10 mg/kg of indomethacin was given; and in the LPS group (n=30), 12 mg/kg of LPS was administered intraperitoneally (IP). In the LPS+indomethacin group (n=32), 10 mg/kg of indomethacin was administered IP simultaneously with 12 mg/kg of LPS. In the L-NAME group (n=6), 20 mg/kg of L-NAME was administered subcutaneously. In LPS+L-NAME group (n=27), 20 mg/kg of L-NAME was administered subcutaneously with 12 mg/kg of LPS IP. All animals were laparotomized 6 h following injections. Existence of IN was noted and blood specimens were obtained. NO was quantified by measurements of nitrite and nitrate, obtaining a total of NO metabolites (NOx). The results were compared using the Mann–Whitney U-test and Spearman correlation test. A value of p<0.05 was considered significant. A total of 17 mice (one in control, 10 in LPS, four in LPS+indomethacin, and two in LPS+L-NAME groups) were excluded from the study because of death or insufficient blood collection. LPS (12 mg/kg, IP) induced IN at a rate of 30% (n=6) in the LPS group. Mean NOx levels were statistically higher in the LPS group (186.67±20.06) compared with other groups (p<0.05). Mean NOx levels were significantly higher in the group of mice with IN than in those without in the LPS group of this study (295.46±16.42, 140.05±15.44, respectively, p<0.05). The mean NOx levels were statistically lower in the LPS+L-NAME(23.94±3.39) group than the LPS+indomethacin (106.77±24.54) group, with no IN detected in neither of these two groups. Increased NOx levels induced by LPS correlated well with the occurrence of IN, and decreasing these levels via COX inhibition by indomethacin or NOS inhibition by L-NAME totally prevented IN from forming in this study. By these observations, it could be concluded that NO is probably involved in the pathophysiology of IN in this experimental model of LPS-induced IN.     

Antipyretic effectiveness of acetaminophen in febrile seizures: Ongoing prophylaxis versus sporadic usage

A controlled clinical study compared the antipyretic effectiveness of acetaminophen administered at regular 4 h intervals (group 1,n=53) versus sproadic usage contingent upon a body temperature above 37.9°C (group 2,n=51) in 104 children presenting with simple febrile convulsions. The incidence of febrile episodes or temperature values were similar in spite of significantly larger amounts of acetaminophen administered to patients in group 1. Four and 4 children in groups 1 and 2, respectively, had a second episode of febrile seizures, in all of them within the first 24 h of admission. We conclude that the prophylactic administration of acetaminophen in children with febrile seizures is not effective in the prevention of fever, the reduction of its degree, or in preventing the early recurrence of febrile seizures.     

Safe use of power injectors with central and peripheral venous access devices for pediatric CT

Purpose. We report our experience in the safe use of power injectors with central and small-gauge peripheral venous access devices for intravenous administration of contrast agent to children undergoing computed tomography (CT) examinations.Materials and methods. We reviewed the medical records of 500 patients randomly selected from the 3121 children who underwent intravenous contrast-enhanced CT examinations at our institution from November 1993 through July 1995.Results. The group of 500 patients, all younger than 18 years of age, accounts for 16 % of the contrast-enhanced CT examinations performed during the study period. Medrad MCT 311 Mark V or Medrad MCT Plus 311 power injectors were used to intravenously administer Omnipaque 300 (2 ml/kg, maximum dose = 150 ml) through venous access devices. These devices comprised Hickman or Broviac lines (n = 228), subcutaneous Port-A-Caths (n = 55), small-gauge butterfly needles (n = 215), and percutaneous intravenous central lines (n = 2). Two complications, one involving a Hickman line and the other a subcutaneous Port-A-Cath, occurred in the study population. These complications correspond to a frequency of 0.4 %. Six cases of contrast extravasation, all of them with the use of 23- (n = 1) and 25-gauge (n = 5) butterfly catheters (frequency = 0.2 %), occurred among the remaining 2621 cases.Conclusion. In light of the low frequency of complications, power injectors and central venous access devices or small-gauge butterfly catheters are safe systems for delivery of intravenous contrast material to pediatric patients. We feel that our strict adherence to manufacturers' guidelines and previously reported techniques partially accounts for our success with these modes of delivery.     

Age effect on whole blood cyclosporine concentrations following oral administration in children with nephrotic syndrome

The aim of this study was to investigate age-related pharmacokinetic differences of cyclosporine (CyA) in children with nephrotic syndrome. Whole blood concentrations of CyA were monitored for a total of 96 times in 36 cases. The 25 male and 11 female patients ranged in age from 1.9 to 19.7 years with a mean age of 9.1 years. Renal biopsy showed minimal change in 33 patients and focal segmental glomerulosclerosis in three patients. CyA was orally administered in two divided doses just before meals. The doses of CyA administered were adjusted such that the target value for blood concentration at 2 h post-dose (C2) was 400–450 ng/ml. The 96 subjects were divided into three groups according to age: group I, 1–5 years (n = 30); group II, 6–10 years (n = 34); and group III, ≥ 11 years (n = 32). In all subjects, peak levels (Cmax) of CyA were reached at C1 or C2. There was no significant difference between the groups for C2, area under the whole blood concentration–time curve up to 4 h post-dose (AUC0–4), and Cmax. The mean CyA doses of groups I, II, and III were 4.8 ± 1.0 mg/kg/day, 3.8 ± 0.9 mg/kg/day, and 3.0 ± 0.6 mg/kg/day, respectively, and there were significant differences between every two groups. In addition, the dose-normalized Cmax (Cmax/dose) and AUC0–4 (AUC0–4/dose) values were significantly lower in the younger group than in the older group. These findings suggested that in children, when the same concentration is targeted, the required CyA dose would vary according to age but would be significantly higher for the younger children.     

Modification of peritoneal ultrafiltration capacity in children undergoing peritoneal dialysis

Eleven children (7 girls and 4 boys) 2 1/2 to 17 years and 8 months of age were treated with CAPD for periods ranging from 6 to 31 months. All children were treated with commercially available dialysate solutions containing lactate. Peritoneal ultrafiltration capacity (PUFC) decreased progressively in all children without accompanying decrease in peritoneal urea and creatinine clearances. Five children developed membrane failure with negative ultrafiltration. One episode of peritonitis occurred in one of these 5 children and in 4 of them only 1.5% glucose solutions had been used. After an initial period (ranging from 14 to 31 months) of CAPD, 2 children were treated with Intermittent Ambulatory Peritoneal Dialysis (IAPD) and two others with Intermittent Cycling Peritoneal Dialysis (ICPD). In these 4 children, PUFC increased within one month from -3.75 ml/kg/day to + 5 ml/kg/day. By providing a shorter dwell time, IAPD and ICPD may allow a reduction in net inward transport of glucose, the maintenance of osmolar gradient and preservation of ultrafiltration capacity. Furthermore, periods of rest may allow some recovery from the progressive deterioration of the peritoneum resulting from long-term irrigation of the peritoneal cavity. These results indicate that IAPD and CPD may be superior to CAPD to maintain the ultrafiltration capacity of the peritoneum.     

Erythropoietin,erythropoesis and iron status in children after major surgical stress

The aim of our study was to evaluate bone marrow stimulation and bone marrow response to post-operative anaemia in children after open heart surgery. In 16 children (age 5.7±0.9 years, weight 20.1±3.2 kg) serum erythropoietin, haematocrit, reticulocyte count, ferritin, transferrin saturation and C-reactive protein were assessed perioperatively after cardiopumonary bypass for surgical repair of atrial septal defect. Erythropoietin increased seven fold from 14±6.2 (7–30) to 80±49 (20–171) mU/ml (P<0.05) and the reticulocyte count a 1.7-fold from 11.1±3.1 (6–19) to 18.4±5.9 (10–31) (P<0.05). Transferrin saturation was inversely correlated to C-reactive protein.Conclusion These findings suggest adequate bone marrow stimulation but an inadequate bone marrow response during the immediate perioperative period, caused by inhibition of erythropoesis by acute postoperative inflammation in children after open heart surgery.     

Pelvic ultrasonography: Early differentiation between isolated premature thelarche and central precocious puberty

We examined 55 girls with isolated premature thelarche between the ages of 0.3 and 7.3 years (group A), 20 children with central precocious puberty between 2.1 and 7.7 years of age and 101 age-matched controls. The children with precocious puberty were divided according to distribution of pubic hair into group B (Tanner stages PH1, B2–3;n=11), representing an early stage of the disorder, and group C (stages PH2–3, B3–4;n=9), representing an advanced stage. Uterine and ovarian volumes were measured sonographically, peak serum levels of luteinizing hormone and folliclestimulating hormone were determined after intravenous administration of luteinizing hormone-releasing hormone. The mean uterine and ovarian volumes were significantly greater in children with precocious puberty than in controls (group B: uterine volume: 3.8±2.0 ml vs 0.9±0.3 ml for controls,P<0.001; ovarian volume: 2.2±1.3 ml vs 0.6±0.2 ml for controls,P<0.01; group C: uterine volume: 8.0±4.4 ml vs 1.0±0.3 ml for controls,P<0.01; ovarian volume: 2.6±1.3 ml vs 0.4±0.1 ml,P<0.01). No significant differences were found between children with premature thelarche and the control group. As a diagnostic method for the early detection of central precocious puberty, ultrasound measurement of uterine volume had a sensitivity and specificity of 100% (cut-off value, 1.8 ml), while ultrasound determination of ovarian volume had a sensitivity of 82% and a specificity of 95% (cut-off value, 1.2 ml). In contrast, as a diagnostic criterion the ratio of levels of luteinizing hormone to follicle-stimulating hormone as determined following stimulation with luteinizing hormone releasing hormone had a sensitivity of 33% and a specificity of 100% (cut-off value, 1.0). Conclusion: ultrasonographic measurement of uterine and ovarian volume offers a reliable means of distinguishing between isolated premature thelarche and early stages of central precocious puberty.     

Evaluation of 25-hydroxyvitamin D and vitamin D binding protein losses in thirteen children on continuous ambulatory peritoneal dialysis

Thirteen children, 6 females, 7 males, aged 2 to 13 years were studied. At the time of study they were on continuous ambulatory peritoneal dialysis (CAPD) for 1 to 22 months. 25-(OH)D loss in daily dialysate fluids represented 2 to 22 micrograms/day. A significant correlation was found between 25-(OH)D plasma concentration and 25-(OH)D dialysate concentration. 25-(OH)D clearance was correlated to 25-(OH)D binding protein clearance (p less than 0.001). These findings of important 25-(OH)D losses in the dialysate fluid of children on CAPD demonstrate the necessity of carefully adapted vitamin D intakes with such a treatment.     

Efficacy of Once Weekly Erythropoietin Therapy in Children on Continuous Ambulatory Peritoneal Dialysis

The efficacy of recombinant human erythropoietin (rHuEPO) on 10 anemic children undergoing continuous ambulatory peritoneal dialysis (CAPD) was evaluated. A mean dose of 93 U/kg of rHuEPO was given once a week for 24 weeks, either intravenously to 5 children or subcutaneously to the other 5. Anemia improved in all children by this therapy. The mean hemoglobin and hematocrit levels increased gradually but significantly from 6.9 g/dl and 20.2% to 9.4 g/dl and 30.1%, respectively, at the end of the study. Elevation of blood pressure or other side effects were not noted in any patient. The present study indicates that the once-a-week injection of rHuEPO by the intravenous or subcutaneous route is effective in children undergoing CAPD.     

Subcutaneous bolus injection of deferoxamine is an alternative method to subcutaneous continuous infusion

The objective of this study was to compare the short- and long-term efficacy of deferoxamine (DFO) given by subcutaneous (SC) continuous infusion over 10 hours via a pump (n = 10) versus a twice-daily subcutaneous bolus injection of the same overall dose (n = 10) in 20 thalassemic children. Urinary iron excretion was measured in 24-hour urine samples after DFO treatment in the 20 patients. The patients were randomized to two groups: 10 patients continued SC continuous infusion with a pump and the remaining 10 received the same overall dose of DFO by twice-daily SC bolus injection for a year. Serum ferritin levels and T1-weighted spin-echo and T2-weighted fast spin-echo signal intensities of liver and paraspinal muscle were determined at initiation and 1 year after initiation of the therapy. In 12 patients, six from each group, liver biopsies were performed and hepatic iron concentration was determined at initiation of therapy and 1 year after treatment. A similar and significant decrease in ferritin levels and improvement in signal intensities of the liver were observed in response to chelation therapy with DFO in both groups (P < 0.01, within each group). Hepatic iron concentration decreased in all patients in the SC bolus injection group (P < 0.05) and in four patients in the SC continuous infusion group (P > 0.05). Hepatic iron concentration was noted to be slightly increased in two patients in the SC continuous infusion group, which may be due to poor compliance. Based on these results, twice-daily SC bolus injection of DFO is as effective as administration via SC continuous infusion using a pump. Subcutaneous bolus injection, being more convenient for the patient, may be a more preferable method of DFO administration.     

Erythropoietin concentrations and erythropoiesis in newborns suffering from renal agenesis and congenital kidney diseases

We studied serum concentrations of erythropoietin (EPO) in the cord blood of 31 newborns. In patients with renal agenesis (n=6), the EPO levels were 68.2 (23–177) mU/ml (median, range). These values are clearly above EPO levels in the reference groups (median/range: <30 weeks 11.0 (5.5–17.5) mU/ml; 30–32 weeks 18.1 (5.5–136) mU/ml; 33–34 weeks 17.7 (8.3–423) mU/ml; 35–37 weeks 17.3 (5.5–272) mU/ml; 38 weeks 17.8 (8.7–40.3) mU/ml). Neonates with polycystic kidney diseases (n=12, EPO 23.5 (9.7–491) mU/ml) and with severe bilateral hydronephrosis due to obstructive uropathy (n=13, 18.6 (7.5–30.7) mU/ml) showed no difference to the reference groups. In all groups there were only slight differences in haemoglobin/haematocrit values.Conclusion In spite of renal agenesis and severe congenital kidney diseases, erythropoiesis is sufficiently maintained during fetal life. The liver of congenitally kidney-damaged fetuses is sufficiently able to compensate the reduction in — or lack of — renal EPO production.     

Subcutaneous recombinant erythropoietin in preterminal renal insufficiency

Recombinant human erythropoietin was given to eight children and adolescents with stable chronic renal failure in the predialysis state. The hormone was administered subcutaneously, twice weekly for 12 weeks, at a starting dose of 50 U/kg per week. The dosage was adapted evekry 4th week. Target haemoglobin was 10.5–11.5 g/dl, and the target haematocrit 32%–35%. Baseline haemoglobin levels of 8.20±0.93 g/dl increased to 9.17±1.10, 10.38±1.18 and 11.19±0.84 g/dl (mean±SD) after 4, 8 and 12 weeks respectively. Serum ferritin levels decreased progressively despite iron supplementation. No side-effects were observed: creatinine clearances remained stable, blood pressure did not increase and none of the patients displayed either convulsions or thrombotic features. The study shows that subcutaneous recombinant human erythropoietin is both effective and safe in anaemic children and adolescents with chronic renal insufficiency.     

Short term correction of anaemia with recombinant human erythropoietin and reduction of cardiac output in end stage renal failure.

Children with end stage renal failure and anaemia have an increased cardiac index and often gross ventricular hypertrophy. The contribution of anaemia to these abnormalities is uncertain. Eleven children with end stage renal failure and anaemia (haemoglobin concentration < 90 g/l) were enrolled into a single blind, placebo controlled, crossover study to assess the cardiovascular effects of reversing anaemia using subcutaneous human recombinant erythropoietin (r-HuEpo). Each limb lasted 24 weeks; seven children completed both limbs of the study. Haemoglobin increased with r-HuEpo, remaining above 100 g/l for a mean of 11 weeks. Cardiac index fell as a result of a reduction in both left ventricular stroke volume and heart rate. Left ventricular end diastolic diameter also decreased. In five children left ventricular wall thickness and left ventricular mass decreased with r-HuEpo, but this failed to reach significance for the whole group. Blood pressure did not change in six normotensive children completing an r-HuEpo limb; the decrease in cardiac index was therefore balanced by an increase in peripheral vascular resistance. Three children were taking anti-hypertensive treatment at the start of the study; one required an increase, and one a decrease, in treatment during the r-HuEpo limb. Short term treatment with r-HuEpo reduces cardiac index. A longer study is needed to determine whether this will, in time, result in a significant reduction in left ventricular hypertrophy.