title: Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates.
abstract: BACKGROUND
  High-dose recombinant human erythropoietin (rEpo) has first been administered in clinical trials for neuroprotection in very preterm neonates at high risk of brain injury and in (near-) term neonates with hypoxic-ischemic encephalopathy. However, recent trials in adults raised concerns about the safety of high-dose rEpo for neuro- and cardioprotection.
  
  
  OBJECTIVE
  To evaluate the putative accumulation or renal leakage of Epo as a function of developmental stage after repetitive early short-term infusion of high-dose rEpo (3 × 3,000 U/kg within 42 h after birth; NCT00413946) for neuroprotection in very preterm infants.
  
  
  METHODS
  Epo concentrations were measured using the ELISA technique in the first two consecutive urine specimens after each rEpo infusion.
  
  
  RESULTS
  Renal Epo excretion was significantly higher in preterm infants with gestational ages <29 weeks than in more mature infants and reached up to 23% of the administered rEpo within 8 h after each infusion. The urinary Epo concentration did not increase after three repetitive infusions of high-dose rEpo. The ratio of urinary Epo to total protein concentrations was the same in infants with gestational ages <29 weeks and in those with gestational ages ≥29 weeks.
  
  
  CONCLUSIONS
  Our data suggest that the higher renal Epo excretion in more immature infants may be attributed to a higher glomerular filtration leakage due to the lower maturation of the kidneys and argue against saturation kinetics after multiple doses of 3,000 U/kg rEpo. This information should be considered in future trials on the use of rEpo for neuroprotection in neonates.
authors: Department of Neonatology, Charité - Universitätsmedizin Berlin, Germany. christof.dame@charite.de
authors: Christof
authors: C
authors: Dame
authors: Juliane
authors: J
authors: Langer
authors: Brigitte M
authors: BM
authors: Koller
authors: Jean-Claude
authors: JC
authors: Fauchère
authors: Hans Ulrich
authors: HU
authors: Bucher
mesh_terms: D000751:Anemia, Neonatal / Q000378:metabolism / Q000517:prevention & control* / Q000652:urine; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology / Q000652:urine*; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000517:prevention & control / Q000652:urine; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology / Q000523:psychology; D007260:Infusion Pumps; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000652:urine; D009994:Osmolar Concentration; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000652:urine; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D010919:Placebos; D011994:Recombinant Proteins; D004921:Erythropoietin