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Abstract: PO1006

Early Change in Albuminuria with Canagliflozin (CANA) Predicts Kidney and Cardiovascular (CV) Outcomes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Oshima, Megumi, The George Institute for Global Health, UNSW Sydney, Sydney, Australia
  • Neuen, Brendon Lange, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Li, Jingwei, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Perkovic, Vlado, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • Charytan, David M., Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, New York, New York, United States
  • de Zeeuw, Dick, Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Edwards, Robert, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Greene, Tom, Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, United States
  • Levin, Adeera, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
  • De Nicola, Luca, Department of Advanced Medical and Surgical Sciences, Nephrology and Dialysis Unit, University Vanvitelli, Naples, Italy
  • Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  • Rosenthal, Norm, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Wheeler, David C., The George Institute for Global Health, UNSW Sydney, Sydney, Australia
  • Jardine, Meg J., The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia
  • L Heerspink, Hiddo Jan, The George Institute for Global Health, UNSW Sydney, Sydney, Australia
Background

The association between early changes in albuminuria and kidney and CV events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association is similar with sodium-glucose cotransporter 2 inhibitors.

Methods

In this post-hoc analysis of the CREDENCE trial in patients with type 2 diabetes and chronic kidney disease, we assessed the effect of CANA versus placebo on albuminuria at week 26, and the association of early changes in urinary albumin:creatinine ratio (UACR) for the first 26 weeks with kidney and CV outcomes using multivariable Cox regression. Kidney and CV outcomes were defined as (1) end-stage kidney disease, doubling of serum creatinine or death due to kidney disease, (2) major adverse cardiovascular events (MACE) and (3) hospitalization for heart failure (HHF) or CV death.

Results

This analysis included 3836 participants (87.2%) with complete data for early changes in UACR. CANA lowered UACR by 31% (95%CI 27–36%) at week 26 and increased the likelihood of achieving a 30% UACR reduction (OR 2.69, 95%CI 2.35–3.07). We observed log-linear associations of early changes in UACR during 26 weeks with kidney and CV outcomes (all p trend <0.001; Table). Each 30% UACR reduction was independently associated with a lower hazard for clinical outcomes, overall and in each treatment arm (all p <0.001).

Conclusion

In people with type 2 diabetes and CKD, canagliflozin results in early and sustained reductions in albuminuria, which was independently associated with long-term kidney and cardiovascular outcomes.