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Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates


Dame, Christof; Langer, Juliane; Koller, Brigitte M; Fauchère, Jean-Claude; Bucher, Hans Ulrich (2012). Urinary erythropoietin concentrations after early short-term infusion of high-dose recombinant epo for neuroprotection in preterm neonates. Neonatology, 102(3):172-177.

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.
OBJECTIVES: 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.

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.
OBJECTIVES: 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neonatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:21 Feb 2013 09:48
Last Modified:16 Jun 2016 12:17
Publisher:Karger
ISSN:1661-7800
Publisher DOI:https://doi.org/10.1159/000339283
PubMed ID:22776958

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