Recombinant human erythropoietin versus placebo or no treatment for the anaemia of chronic kidney disease in people not requiring dialysis

Cochrane Database Syst Rev. 2016 Jan 20;2016(1):CD003266. doi: 10.1002/14651858.CD003266.pub3.


Background: Treatment with recombinant human erythropoietin (rHuEPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHuEPO use in predialysis patients which may accelerate the deterioration of kidney function. However the opposing view is that if rHuEPO is as effective in predialysis patients, improving the patient's sense of well-being may result in the onset of dialysis being delayed. This is an update of a review first published in 2001 and last updated in 2005.

Objectives: The objective of this review was to ascertain the effects of rHuEPO treatment in predialysis patients primarily in terms of the timing of the onset of dialysis; but also that predialysis rHuEPO: 1) corrects haemoglobin/haematocrit (markers of anaemia); 2) improves quality of life; and 3) is not associated with an increased incidence of adverse events such as hastening of the onset of dialysis, increased hypertension, clotting of arterio-venous fistulae or seizures.

Search methods: We searched the Cochrane Kidney and Transplant's Specialised Register (up to 29 June 2015) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: Randomised controlled trials (RCTs) or quasi-RCTs comparing the use of rHuEPO with no treatment or placebo in predialysis patients.

Data collection and analysis: Only published data were used. Quality assessment was performed by two assessors independently. Data were abstracted by a single author onto a standard form, a sample of which was checked by another author. Results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).

Main results: Nineteen studies (enrolling 993 participants) were included. Due to the age of the included studies (most performed prior to 2000) the risk of bias was judged to be unclear in the majority of the studies for most of the domains. There was an improvement in haemoglobin (MD 1.90 gm/L, 95% CI -2.34 to -1.47) and haematocrit (MD 9.85%, 95% CI 8.35 to 11.34) with treatment and a decrease in the number of patients requiring blood transfusions (RR 0.32, 95% CI 0.12 to 0.83). The data from studies reporting quality of life or exercise capacity demonstrated an improvement in the treatment group. Most of the measures of progression of kidney disease showed no statistically significant difference. No significant increase in adverse events was identified.

Authors' conclusions: Treatment with rHuEPO in predialysis patients corrects anaemia, avoids the requirement for blood transfusions and also improves quality of life and exercise capacity. We were unable to assess the effects of rHuEPO on progression of kidney disease, delay in the onset of dialysis or adverse events. Based on the current evidence, decisions on the putative benefits in terms of quality of life are worth the extra costs of predialysis rHuEPO need careful evaluation.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anemia / blood
  • Anemia / drug therapy*
  • Anemia / etiology
  • Disease Progression
  • Erythropoietin / adverse effects
  • Erythropoietin / therapeutic use*
  • Hematocrit
  • Humans
  • Kidney Failure, Chronic / complications*
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use


  • Recombinant Proteins
  • Erythropoietin