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Abstract: TH-PO687

Erythropoiesis-Stimulating Agent (ESA) Hyporesponsiveness and Major Adverse Cardiovascular Events: Results From ASCEND-D

Session Information

  • Anemia and Iron Metabolism
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • McCausland, Finnian R., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Waikar, Sushrut S., Boston University School of Medicine, Boston, Massachusetts, United States
  • Claggett, Brian, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • McMahon, Gearoid M., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Vieira Neto, Osvaldo Merege, Serviço de Nefrologia de Ribeirao Preto, São Paulo, Brazil
  • Rastogi, Anjay, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, United States
  • Praditpornsilpa, Kearkiat, Chulalongkorn University, Bangkok, Bangkok, Thailand
  • Correa-Rotter, Ricardo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico, Mexico
  • Kher, Vijay K., Medanta The Medicity Medanta Institute of Kidney and Urology, Gurugram, Haryana, India
  • Del Vecchio, Lucia, Sant'Anna Hospital, Como, Italy
  • Singh, Ajay K., Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Hyporesponsiveness to ESAs is associated with adverse cardiovascular (CV) outcomes. Although several definitions exist, data examining associations with CV outcomes in clinical trials are limited.

Methods

ASCEND-D (NCT02879305) randomized 2,964 patients on chronic dialysis to daprodustat or conventional ESAs. All received an ESA for at least 6 weeks prior to randomization and were managed with dosing algorithms for iron and randomized treatment. Three definitions of hyporesponsiveness were prespecified: 1)erythropoietin resistance index (ERI) ≥2U/kg/wk/g/L or prior ESA dose/estimated dry weight ≥450U/kg/wk; 2) ERI ≥1.5U/kg/wk/g/L; 3) baseline ESA dose (U/week) in top 20th %ile. Cox models examined associations of each definition with the CV composite (death, myocardial infarction, stroke), adjusted for dialysis modality, region, age, sex, race, dialysis vintage, CV disease, diabetes, serum albumin, SBP, hemoglobin, and C-reactive protein. Interaction terms were included to assess for effect modification by randomized treatment.

Results

Baseline ESA hyporesponsiveness was present in 12%, 20%, and 20% of patients for definitions HypoR1, HypoR2, and HypoR3, respectively. Compared to no hyporesponsiveness, all definitions had quantitatively similar associations with the CV outcome: hazard ratio [HR] 1.54 (95%CI 1.24-1.91) for HypoR1 (Figure); HR 1.46; 95%CI 1.22-1.76) for HypoR2; HR 1.45 (95%CI 1.21-1.74) for HypoR3. There was no evidence for effect modification by treatment (P-interaction >0.40 for all).

Conclusion

Baseline ESA hyporesponsiveness is a potent predictor of CV outcomes in ASCEND-D. All pre-specified definitions provided similar predictive abilities.

Funding

  • Commercial Support