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Abstract: TH-OR08

Regional Variation of Erythropoietin-Stimulating Agent Hyporesponsiveness in the Global Daprodustat Dialysis Study (ASCEND-D)

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism


  • Singh, Ajay K., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Blackorby, Allison, GlaxoSmithKline, Research Triangle Park, North Carolina, United States
  • Cizman, Borut, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Cobitz, Alexander Ralph, GlaxoSmithKline, Collegeville, Pennsylvania, United States
  • Godoy, Sergio Ariel, George Clinical, Pilar, Argentina
  • Jha, Vivekanand, George Institute for Global Health, Sydney, New South Wales, Australia
  • Johansen, Kirsten L., Hennepin Healthcare, Minneapolis, Minnesota, United States
  • McMahon, Gearoid M., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Meadowcroft, Amy M., GlaxoSmithKline, Research Triangle Park, North Carolina, United States
  • Obrador, Gregorio T., Universidad Panamericana, Mexico, DF, Mexico
  • Wong, Muh Geot, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  • Macdougall, Iain C., King's College Hospital, London, London, United Kingdom

Hyporesponsiveness to erythropoiesis-stimulating agents (ESA) is present in 10%–15% of the prevalent dialysis population. We explored baseline characteristics and predictors of ESA hyporesponsiveness in a global randomized cardiovascular outcomes study comparing an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), daprodustat, with conventional ESA treatment.


ASCEND-D (NCT02879305) recruited 2964 prevalent dialysis patients receiving ESA treatment (standardized to weekly intravenous [IV] epoetin) who were iron replete at baseline. Primary ESA hyporesponsiveness definition: ESA Resistance Index (ERI, ESA Units/kg/week/hemoglobin g/L) ≥2 or IV ESA equivalent dose ≥450 Units/kg/week. Predictors of ESA hyporesponsiveness were determined using a multivariable regression model. Alternate hyporesponder definitions were explored.


Using the primary definition, 354 (12%) patients were ESA hyporesponsive. Selected baseline characteristics in the overall population and by ESA responsiveness, along with the results from the multivariable analysis, are shown below. Additional predictors of ESA hyporesponsiveness include a history of heart failure (0.013), dialysis vintage (0.033), smoking status (0.046), aspirin use (0.039), and ACEi/ARB use (0.081).


This is the first global HIF-PHI study to report pre-specified definitions and predictors of ESA hyporesponsiveness. While most of the strong predictors identified in our study have been previously reported, geographic region stands out as an unexpected finding that requires further investigation.


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