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

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

Recombinant human erythropoietin in sports: a review

Erythropoietin is an endogenous hormone of glicoproteic nature secreted by the kidneys and is the main regulator of the erythropoiesis. An alteration in its production generates a disturbance in the plasmatic concentration giving rise to several types of pathologies related to the hematopoietic system. The recombinant forms of erythropoietin have indiscriminately been used by athletes, mainly in endurance sports, by increasing the erythrocytes concentration, generating a better delivery of oxygen to the muscle tissue. The administration of recombinant erythropoietin was prohibited by the International Olympic Committee and its use considered as doping. This review has the intention to describe the physical, biological and pharmacokinetic properties of the endogenous erythropoietin, as well as its recombinant form, describing also its use in sports and the process of searching methodologies for its detection in doping control