title: Inflammation and resistance to treatment with recombinant human erythropoietin.
abstract: 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.
authors.affiliation: Department of Nephrology and Dialysis, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Vecchio
authors.forename: Pietro
authors.initials: P
authors.lastname: Pozzoni
authors.forename: Simeone
authors.initials: S
authors.lastname: Andrulli
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D002908:Chronic Disease; D000068256:Darbepoetin alfa; D004351:Drug Resistance; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000150:complications; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D044342:Malnutrition; D011502:Protein-Energy Malnutrition / Q000209:etiology; D011994:Recombinant Proteins; D006435:Renal Dialysis
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa