Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients

PLoS One. 2016 Mar 3;11(3):e0148938. doi: 10.1371/journal.pone.0148938. eCollection 2016.


Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients.

MeSH terms

  • Aged
  • Anemia / blood
  • Anemia / complications
  • Anemia / pathology
  • Anemia / therapy*
  • Darbepoetin alfa / blood
  • Darbepoetin alfa / therapeutic use*
  • Disease Management
  • Erythropoiesis / drug effects
  • Female
  • Ferric Compounds / blood
  • Ferric Compounds / therapeutic use*
  • Ferric Oxide, Saccharated
  • Glucaric Acid / blood
  • Glucaric Acid / therapeutic use*
  • Hematinics / blood
  • Hematinics / therapeutic use*
  • Hemoglobins / biosynthesis*
  • Humans
  • Injections, Intravenous
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Models, Statistical*
  • Neural Networks, Computer
  • Renal Dialysis
  • Retrospective Studies


  • Ferric Compounds
  • Hematinics
  • Hemoglobins
  • Darbepoetin alfa
  • Ferric Oxide, Saccharated
  • Glucaric Acid

Grant support

The authors have no support or funding to report.