title: Erythropoietin resistance and survival in non-dialysis patients with stage 4-5 chronic kidney disease and heart disease.
abstract: BACKGROUND
  Patients with chronic kidney disease (CKD) frequently suffer from heart disease as well. The combination of the two processes can exacerbate inflammation, resulting in increases in both resistance to erythropoietin (EPO) and mortality.
  
  
  OBJECTIVE
  The aim of this study was to determine the prevalence of heart disease in a representative group of non-dialysis patients with stage 4-5 CKD, and the influence of that entity on EPO requirements and on mortality during a period of 36 months.
  
  
  METHODS
  134 patients (68% on EPO at the beginning, increasing to 72.3% during follow-up) were monitored for 36 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI) calculated as the weekly weight-adjusted dose of EPO divided by the haemoglobin level. The ERI was determined both initially and during the last six months before the end of the study.
  
  
  RESULTS
  39 patients (29.1%) had history of heart disease; 22 (16.4%) had suffered from heart failure (HF). The ERI was higher in patients with a history of heart disease or HF and those treated with drugs acting on the renin-angiotensin system (ACE inhibitors or ARBs). Using ERI as the dependent variable in the multivariate analysis, the variables that composed the final model were ferritin, haemoglobin, glomerular filtration rate and history of HF. The 36 month mortality rate (n=39 patients) was higher in the group having ERI above the median (2.6IU/week/kg/gram of haemoglobin in 100ml) (P=.002), and in the groups with heart disease (P=.001) or HF (P=.001) according to the Kaplan-Meier survival analysis.
  
  
  CONCLUSIONS
  Patients with history of heart disease or HF have a higher ERI, and all of these characteristics are associated with lower survival. ERI can be considered a marker for risk of death in the short to-medium term.
authors.affiliation: Nefrología. Hospital Virgen del Rocio, Sevilla, Spain. mguerrerror@yahoo.es
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Guerrero-Riscos
authors.forename: Rafael
authors.initials: R
authors.lastname: Montes-Delgado
authors.forename: María
authors.initials: M
authors.lastname: Seda-Guzmán
authors.forename: Juan M
authors.initials: JM
authors.lastname: Praena-Fernández
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001327:Autoimmune Diseases / Q000453:epidemiology; D059347:Cardio-Renal Syndrome / Q000097:blood / Q000401:mortality*; D002317:Cardiovascular Agents / Q000627:therapeutic use; D015897:Comorbidity; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005293:Ferritins / Q000097:blood; D005919:Glomerular Filtration Rate; D006331:Heart Diseases / Q000188:drug therapy / Q000453:epidemiology; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012720:Severity of Illness Index
chemical_list: D002317:Cardiovascular Agents; D006454:Hemoglobins; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D005293:Ferritins