Kidney Week

Abstract: PO1001

Acute Declines in eGFR During Treatment with Canagliflozin (CANA) and Its Implications for Clinical Practice: Insights from CREDENCE

Session Information

• Diabetic Kidney Disease: Clinical - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• L Heerspink, Hiddo Jan, The George Institute for Global Health, Sydney, Australia

Hiddo Jan L Heerspink,

• Oshima, Megumi, The George Institute for Global Health, Sydney, Australia

Megumi Oshima,

• Jardine, Meg J., The George Institute for Global Health, Sydney, New South Wales, Australia

Meg J. Jardine,

• Agarwal, Rajiv, Indiana University School of Medicine and Veterans Affairs Medical Center, Indianapolis, Indiana, United States

Rajiv Agarwal,

• Bakris, George L., Department of Medicine, University of Chicago Medicine, Chicago, Illinois, United States

George L. Bakris,

• Cannon, Christopher P., Cardiovascular Division, Baim Institute for Clinical Research, Boston, Massachusetts, United States

Christopher P. Cannon,

• Charytan, David M., Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, New York, New York, United States

David M. Charytan,

• de Zeeuw, Dick, Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Dick de Zeeuw,

• Edwards, Robert, Janssen Research & Development, LLC, Raritan, New Jersey, United States

Robert Edwards,

• Greene, Tom, Division of Biostatistics, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah, United States

Tom Greene,

• Levin, Adeera, Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada

Adeera Levin,

• Mahaffey, Kenneth W., Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, California, United States

Kenneth W. Mahaffey,

• Neal, Bruce, The George Institute for Global Health, Sydney, New South Wales, Australia

Bruce Neal,

• Pollock, Carol A., Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales, Australia

Carol A. Pollock,

• Rosenthal, Norm, Janssen Research & Development, LLC, Raritan, New Jersey, United States

Norm Rosenthal,

• Wheeler, David C., Department of Renal Medicine, UCL Medical School, London, United Kingdom

David C. Wheeler,

• Zhang, Hong, Renal Division of Peking University First Hospital, Beijing, China

Hong Zhang,

• Zinman, Bernard, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

Bernard Zinman,

• Perkovic, Vlado, The George Institute for Global Health, Sydney, New South Wales, Australia

Vlado Perkovic,

Background

CANA slows progression of chronic kidney disease (CKD) in people with type 2 diabetes. CANA also induces a reversible acute decline in estimated glomerular filtration rate (eGFR), which is believed to be a hemodynamic effect. Predictors of the initial decline and its association with long-term eGFR trajectories and safety outcomes are unknown.

Methods

This post hoc study of CREDENCE included 4289 patients with type 2 diabetes and CKD who had eGFR measured at both baseline and week 3. Participants were categorized by percentage decline in eGFR at week 3: greater than 10% decline; between 0 and 10% decline; and no decline. Baseline characteristics associated with acute eGFR drop >10% were evaluated using logistic regression. Long-term eGFR decline and safety outcomes were estimated in each eGFR decline category by linear mixed effects models and Cox regression after adjustment for laboratory measures and medication use.

Results

More participants in the CANA (956 [45%]) versus placebo (PBO) group (450 [21%]) had an acute eGFR decline >10% (p<0.001). A >30% decline occurred infrequently (89 [4%] with CANA and 39 [2%] with PBO; p<0.001). In the CANA but not in the PBO group, older age (OR CANA 1.17, 95% CI 1.05–1.31; per 10 years) and history of heart failure (OR CANA 0.77, 0.59–0.99) were associated with a higher and lower likelihood of an acute eGFR decline >10%, respectively (both p interaction<0.05). Following the initial eGFR change, long-term eGFR trajectories were similar across eGFR decline categories (all p>0.05). Safety profiles were also similar except when the drop unusually exceeded 30%, in which case adverse events and renal related adverse events occurred more frequently. Results were consistent in subgroup analysis by baseline eGFR (30-<45, 45-<60, and 60-<90 mL/min/1.73m²).

Conclusion

Although acute eGFR declines >10% occurred in nearly half of all patients following initiation of CANA, the benefit of CANA compared with PBO was observed regardless of the acute eGFR decline and safety profiles were similar.

Funding

• Commercial Support –