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Kidney Week

Abstract: TH-PO1202

Canagliflozin (CANA) Slows Declines in Kidney Function in People with Baseline (BL) eGFR <30 mL/min/1.73 m2

Session Information

Category: Diabetic Kidney Disease

Authors

  • Bakris, George L., Department of Medicine, University of Chicago Medicine, Chicago, Chicago, Illinois, United States
  • Oshima, Megumi, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia
  • Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
  • Brenner, Barry M., Renal Division and Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School and Baim Institute for Clinical Research, Wellesley, Massachusetts, United States
  • Charytan, David M., Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, New York, NY, USA and Baim Institute for Clinical Research, Bronx, New York, United States
  • Levin, Adeera, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
  • Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
  • Wheeler, David C., Department of Renal Medicine, UCL Medical School, London, London, United Kingdom
  • Zhang, Hong, Renal Division of Peking University First Hospital, Beijing, China
  • Greene, Tom, Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, United States
  • Capuano, George, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Edwards, Robert, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Oh, Richard, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Rosenthal, Norm, Janssen Research & Development, LLC, Raritan, New Jersey, United States
  • Jardine, Meg J., The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia
  • Perkovic, Vlado, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia
Background

The CREDENCE trial demonstrated that the SGLT2 inhibitor CANA significantly reduced kidney failure and cardiovascular (CV) events in participants with type 2 diabetes and chronic kidney disease. During the study, participants continued treatment until initiation of dialysis or kidney transplantation. The efficacy and safety of CANA in the subgroup of participants with BL eGFR <30 mL/min/1.73 m2 were evaluated.

Methods

While eligibility, in part, required a screening eGFR of 30-90 mL/min/1.73 m2, BL assessment of eGFR performed at the randomization visit could fall outside of the indicated range. Efficacy and incidence of selected adverse events were examined in those with a BL eGFR <30 mL/min/1.73 m2, a subgroup defined post hoc. Effects of on-treatment eGFR slope were analyzed using a piecewise, 2-slope linear mixed effects model with a knot at week 3, with compound symmetry fitted where unstructured models did not converge. Treatment effects for other renal outcomes are expressed hazard ratios (HRs) with 95% CI.

Results

Overall, 174 (4%) participants had BL eGFR <30 mL/min/1.73 m2. Mean annual change in eGFR for placebo- and CANA-treated participants was –4.00 and –1.50 mL/min/1.73 m2 (placebo-subtracted difference: 2.50 mL/min/1.73 m2, 95% CI: 0.55–4.44). Numerical trends favoring CANA were noted for ESKD (HR: 0.67; 95% CI: 0.35–1.27], primarily driven by risk reduction in time to eGFR <15 mL/min/1.73 m2 (HR: 0.50; 95% CI: 0.25–1.02) as compared to initiation of dialysis/kidney transplantation (HR: 0.90; 95% CI: 0.39–2.06). Doubling of serum creatinine similarly favored CANA (HR: 0.72; 95% CI: 0.34–1.54). CV outcomes were not different between groups, although results were broadly consistent with the overall population. Acute kidney injury events were similar for CANA compared with placebo (10.7% and 11.1%).

Conclusion

Among a subgroup of participants with BL eGFR <30 mL/min/1.73 m2, CANA reduced the rate of eGFR decline and slowed progression to ESKD. The renal and CV outcome comparisons were consistent with results in the overall study population.

Funding

  • Commercial Support