title: High-dose erythropoietin for tissue protection.
abstract: BACKGROUND
  The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction. Experimental studies have been favourable, but the clinical efficacy has yet to be validated.
  
  
  METHODS
  We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of rHuEPO for this indication. A systematic literature search was performed using the PubMed/MEDLINE database for randomized, placebo-controlled clinical trials.
  
  
  RESULTS
  Twenty-six randomized controlled trials that enrolled 3176 patients were included. The majority of trials (20 trials including 2724 patients) reported no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality.
  
  
  CONCLUSIONS
  Evidence is sparse to support a tissue-protective benefit of rHuEPO in humans. Moreover, a number of studies indicate that short-term administration of high-dose rHuEPO is associated with an increased risk of mortality and serious adverse events. Further work is needed to elucidate the mechanisms of toxicity of rHuEPO in humans.
authors.affiliation: Department of Neuroscience and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anton
authors.initials: A
authors.lastname: Lund
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
authors.forename: Niels V
authors.initials: NV
authors.lastname: Olsen
mesh_terms: D002316:Cardiotonic Agents / Q000008:administration & dosage; D019610:Cytoprotection / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D007674:Kidney Diseases / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D002316:Cardiotonic Agents; D006397:Hematinics; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: Cardioprotection; erythropoiesis stimulating agent; erythropoietin; nephroprotection; neuroprotection