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Kidney Week

Abstract: TH-PO184

Autoantibodies to Erythropoietin Receptor and Clinical Outcomes in Patients with Type 2 Diabetes and CKD: A Post Hoc Analysis of the CREDENCE Trial

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Koshino, Akihiko, University Medical Center Groningen, Groningen, Netherlands
  • Neuen, Brendon Lange, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Oshima, Megumi, Kanazawa University, Kanazawa, Ishikawa, Japan
  • Toyama, Tadashi, Kanazawa University, Kanazawa, Ishikawa, Japan
  • Hara, Akinori, Kanazawa University, Kanazawa, Ishikawa, Japan
  • Arnott, Clare Gabrielle, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Neal, Bruce, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Jardine, Meg, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Badve, Sunil, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, California, United States
  • Pollock, Carol A., Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
  • Hansen, Michael K., Janssen Research and Development LLC, Spring House, Pennsylvania, United States
  • Wada, Takashi, Kanazawa University, Kanazawa, Ishikawa, Japan
  • Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands
Background

Anti-erythropoietin receptor (EPOR) antibodies have been identified in patients with various kidney diseases. This study aimed to assess the association of anti-EPOR antibodies with kidney, cardiovascular and mortality outcomes in the CREDENCE trial, and to determine whether the effects of canagliflozin on hemoglobin and hematocrit were modified by anti-EPOR antibodies.

Methods

Patients with type 2 diabetes (T2D) and CKD were randomly assigned to receive canagliflozin 100mg daily or a matching placebo. Serum anti-EPOR antibodies at baseline were measured using an indirect enzyme-linked immunosorbent assay. The primary composite outcome consisted of a doubling of serum creatinine, end-stage kidney disease, or death from kidney or cardiovascular reasons. The secondary outcome was death from any cause. Multivariable adjusted Cox proportional hazard regression was used to estimate associations between anti-EPOR antibodies and outcomes. The effects of canagliflozin on hemoglobin and hematocrit over time were assessed with a repeated measures mixed effect model.

Results

Of 2600 (59.1%) CREDENCE participants with available samples, 191 (7.3%) were positive for anti-EPOR antibodies. During a median follow-up of 2.8 years, the primary composite outcome and all-cause death occurred in 348 (13.4%) and 227 (8.7%) individuals, respectively. Higher baseline levels of anti-EPOR antibodies were independently associated with increased risk of the primary outcome (HR per 1-SD increase 1.12 [95%CI 1.01, 1.24], p=0.04) and all-cause death (HR 1.27 [95%CI 1.08, 1.48], p<0.01). Canagliflozin, compared to placebo, increased hemoglobin and hematocrit by 7.0 g/L (95%CI 6.2, 7.9, p<0.01) and 2.4% (95%CI 2.2, 2.7, p<0.01), respectively. These effects were consistent in patients with and without anti-EPOR antibodies (p-interaction=0.39 and 0.70).

Conclusion

In patients with T2D and CKD, anti-EPOR antibodies were associated with the composite kidney and cardiovascular outcome and all-cause mortality. Canagliflozin increased hemoglobin and hematocrit regardless of the presence of anti-EPOR antibodies.

Funding

  • Commercial Support – Janssen Research and Development