Kidney Week

Abstract: TH-OR08

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

Session Information

• Breakthroughs in Anemia and Iron Management
  October 22, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Anemia and Iron Metabolism

• 200 Anemia and Iron Metabolism

Authors

• Singh, Ajay K., Brigham and Women's Hospital, Boston, Massachusetts, United States

Ajay K. Singh, MD



Dr Ajay Singh is a member of the Renal Division at the Brigham and Women's Hospital and faculty and Senior Associate Dean for Postgraduate Medical Education at Harvard Medical School. Dr. Singh was PI for the CHOIR Study, a member of the executive committee for the TREAT study and DRIVE study. Currently, he chairs the executive steering committee for the ASCEND Clinical Trial Program sponsored by GSK. The ASCEND program includes two large global cardiovascular outcome trials in maintenance dialysis and non-dialysis CKD patients and one smaller trial in incident dialysis patients that aims to test the efficacy and safety of the daprodustat, a novel PHI.

• Blackorby, Allison, GlaxoSmithKline, Research Triangle Park, North Carolina, United States

Allison Blackorby,

• Cizman, Borut, GlaxoSmithKline, Collegeville, Pennsylvania, United States

Borut Cizman,

• Cobitz, Alexander Ralph, GlaxoSmithKline, Collegeville, Pennsylvania, United States

Alexander Ralph Cobitz,

• Godoy, Sergio Ariel, George Clinical, Pilar, Argentina

Sergio Ariel Godoy,

• Jha, Vivekanand, George Institute for Global Health, Sydney, New South Wales, Australia

Vivekanand Jha,

• Johansen, Kirsten L., Hennepin Healthcare, Minneapolis, Minnesota, United States

Kirsten L. Johansen,

• McMahon, Gearoid M., Brigham and Women's Hospital, Boston, Massachusetts, United States

Gearoid M. McMahon,

• Meadowcroft, Amy M., GlaxoSmithKline, Research Triangle Park, North Carolina, United States

Amy M. Meadowcroft,

• Obrador, Gregorio T., Universidad Panamericana, Mexico, DF, Mexico

Gregorio T. Obrador,

• Wong, Muh Geot, Royal North Shore Hospital, St Leonards, New South Wales, Australia

Muh Geot Wong,

• Macdougall, Iain C., King's College Hospital, London, London, United Kingdom

Iain C. Macdougall,

Background

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.

Methods

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.

Results

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).

Conclusion

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.

Funding

• Commercial Support –