Anaemia and resistance to erythropoiesis-stimulating agents as prognostic factors in haemodialysis patients: results from the RISCAVID study

Nephrol Dial Transplant. 2011 Aug;26(8):2641-8. doi: 10.1093/ndt/gfq802. Epub 2011 Feb 16.


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.

MeSH terms

  • Aged
  • Anemia / complications*
  • Anemia / drug therapy*
  • Anemia / mortality
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Drug Resistance*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Hematinics / adverse effects*
  • Humans
  • Inflammation / etiology*
  • Inflammation / mortality
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / mortality*
  • Kidney Failure, Chronic / therapy
  • Kidney Function Tests
  • Male
  • Prognosis
  • Renal Dialysis / adverse effects*
  • Renal Dialysis / methods
  • Survival Rate


  • Biomarkers
  • Hematinics
  • C-Reactive Protein