Inflammation and resistance to treatment with recombinant human erythropoietin

J Ren Nutr. 2005 Jan;15(1):137-41. doi: 10.1053/j.jrn.2004.09.024.


Despite an increase in the use and average dose of recombinant human EPO (rh-EPO) over the last 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. The definition of rh-EPO resistance has been introduced to identify those patients in whom the target hemoglobin level is not attained despite a greater-than-usual dose of erythropoietin-stimulating agent (ESA). In recent years, increasing attention has been paid to the relationship between dialysis, increased inflammatory stimulus, malnutrition, and ESA response. About 35% to 65% of hemodialysis patients show signs of inflammation that could be a cause of anemia through the suppression of bone marrow erythropoiesis by a number of cytokines. A large proportion of chronic kidney disease patients also have protein-energy malnutrition and wasting; low serum albumin levels, together with other more specific nutritional markers, are predictors of rh-EPO response. A diminished nutritional state could then be a feature of patients who are resistant to ESA treatment, with malnutrition probably being a consequence of a chronic inflammatory state. Starting from the hypothesis that anemia, partially attributable to a reduced response to ESA, could be the link among malnutrition, inflammation, and the poor outcome of chronic kidney disease patients, we designed a multicenter observational study, the Malnutrition-Inflammation-Resistance-Treatment Outcome Study (MIRTOS), aimed at evaluating the impact and possible causes of resistance to ESA in a large sample of hemodialysis patients. We hope the results of MIRTOS will represent a step forward toward a better understanding of the factors influencing the response to ESA in hemodialysis patients.

Publication types

  • Comparative Study

MeSH terms

  • Anemia / drug therapy
  • Anemia / etiology
  • Chronic Disease
  • Darbepoetin alfa
  • Drug Resistance*
  • Epoetin Alfa
  • Erythropoietin / administration & dosage
  • Erythropoietin / analogs & derivatives
  • Erythropoietin / therapeutic use*
  • Hemoglobins / analysis
  • Humans
  • Inflammation* / complications
  • Kidney Diseases / complications*
  • Kidney Diseases / therapy
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Malnutrition
  • Protein-Energy Malnutrition / etiology
  • Recombinant Proteins
  • Renal Dialysis


  • Hemoglobins
  • Recombinant Proteins
  • epoetin beta
  • Erythropoietin
  • Darbepoetin alfa
  • Epoetin Alfa