title: Anaemia and resistance to erythropoiesis-stimulating agents as prognostic factors in haemodialysis patients: results from the RISCAVID study.
abstract: BACKGROUND
  Resistance to erythropoiesis-stimulating agents (ESAs) is often associated with chronic inflammation. Here, we investigated how anaemia, ESA resistance and the plasma levels of biological markers of inflammation could influence all-cause and cardiovascular disease morbidity and mortality.
  
  
  METHODS
  Seven hundred and fifty-three haemodialysis (HD) patients (mean age 66 ± 14.2 years, mean dialytic age 70 ± 77 months and diabetes 18.8%) were enrolled and followed-up for 36 months. Demographic, clinical and laboratory data, co-morbidity conditions, administered drugs, all-cause mortality and fatal/non-fatal cardiovascular (CV) events were recorded. We measured ESA resistance index, C-reactive protein (CRP) and interleukin-6 (IL-6).
  
  
  RESULTS
  Six hundred and fifty-one patients (86.4%) received ESAs. Patients with haemoglobin level <11 g/dL (n = 225) showed increased risk of CV [relative risk (RR) 1.415, 95% confidence interval (CI) 1.046-1.914] and overall mortality (RR 1.897, 95% CI 1.423-2.530) versus patients with haemoglobin levels >11 g/dL. ESA resistance values categorized into quartiles (Quartile I <5.6, Quartile II 5.7-9.6, Quartile III 9.7-15.4 and Quartile IV >15.4) correlated with all-cause mortality and fatal/non-fatal CV events (RR 1.97, 95% CI 1.392-2.786; RR 1.619, 95% CI 1.123-2.332, respectively). Furthermore, albumin was significantly reduced versus reference patients and correlated with all-cause mortality and CV events; CRP levels were higher in hyporesponders (Quartile IV) (P < 0.001) and predicted all-cause mortality and CV events. IL-6 but not CRP was a strong predictor of ESA resistance.
  
  
  CONCLUSIONS
  ESA responsiveness can be considered a strong prognostic factor in HD patients and seems to be tightly related to protein-energy wasting and inflammation.
authors.affiliation: Nephrology and Dialysis Versilia Hospital, Versilia, Italy. vpanichi@usl12.toscana.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panichi
authors.forename: Alberto
authors.initials: A
authors.lastname: Rosati
authors.forename: Roberto
authors.initials: R
authors.lastname: Bigazzi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Paoletti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mantuano
authors.forename: Sara
authors.initials: S
authors.lastname: Beati
authors.forename: Valentina
authors.initials: V
authors.lastname: Marchetti
authors.forename: Giada
authors.initials: G
authors.lastname: Bernabini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Grazi
authors.forename: Giovanni Manca
authors.initials: GM
authors.lastname: Rizza
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Migliori
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giusti
authors.forename: Alberto
authors.initials: A
authors.lastname: Lippi
authors.forename: Aldo
authors.initials: A
authors.lastname: Casani
authors.forename: Giuliano
authors.initials: G
authors.lastname: Barsotti
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
mesh_terms: D000368:Aged; D000740:Anemia / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006397:Hematinics / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000401:mortality; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy; D007677:Kidney Function Tests; D008297:Male; D011379:Prognosis; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D006397:Hematinics; D002097:C-Reactive Protein