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Abstract: FR-OR51

The Effect of Dapagliflozin on Rate of Kidney Function Decline in Patients with CKD: A Prespecified Analysis from the DAPA-CKD Trial

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • L Heerspink, Hiddo Jan, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Jongs, Niels, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
  • Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States
  • Langkilde, Anna Maria, AstraZeneca, Gothenburg, Sweden
  • McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom
  • Correa-Rotter, Ricardo, The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Sjostrom, David, AstraZeneca, Gothenburg, Sweden
  • Stefansson, Bergur V., AstraZeneca, Gothenburg, Sweden
  • Toto, Robert D., UT Southwestern Medical Center, Dallas, Texas, United States
  • Wheeler, David C., University College London, London, London, United Kingdom
  • Greene, Tom, University of Utah Health, Salt Lake City, Utah, United States
Background

Dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease (CKD) with and without type 2 diabetes in the DAPA-CKD trial (NCT03036150). This pre-specified analysis assessed the effect of dapagliflozin on the rate of change in estimated glomerular filtration rate (eGFR) slope.

Methods

DAPA-CKD randomized 4304 participants with urinary albumin-to-creatinine ratio (UACR) 200–5000 mg/g and eGFR 25–75 mL/min/1.73m2 to dapagliflozin 10 mg or placebo once daily, added to standard care. We analysed eGFR slope using mixed effect models with different slopes from baseline to Week 2 (acute change); Week 2 to end-of-treatment (chronic eGFR slope); and baseline to end-of-treatment at median 2.3 years (total eGFR slope).

Results

In the overall cohort, dapagliflozin compared to placebo slowed mean eGFR decline from baseline to end-of-treatment by 0.9 mL/min/1.73m2/year (95%CI 0.6–1.3). Dapagliflozin compared with placebo caused an acute eGFR decline of 2.6 mL/min/1.73m2 (95%CI 2.2–3.1) and 2.0 mL/min/1.73m2 (95%CI 1.4–2.7), in patients with and without type 2 diabetes, respectively. Thereafter, dapagliflozin compared to placebo reduced the mean rate of eGFR decline by a greater amount in patients with type 2 diabetes (chronic eGFR slope mean difference 2.3 mL/min/1.73m2/year [95%CI 1.9–2.6]) than in those without type 2 diabetes (1.3 mL/min/1.73m2/year [95%CI 0.7–1.8]; interaction p=0.005). The effect of dapagliflozin compared to placebo on total slope in patients with and without type 2 diabetes was 1.2 mL/min/1.73m2/year (95%CI 0.8–1.6) and 0.5 mL/min/1.73m2/year (95%CI −0.1–1.0; interaction p=0.04), respectively. The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the beneficial effect of dapagliflozin on eGFR slope was also more pronounced in patients with higher baseline HbA1c and UACR.

Conclusion

Dapagliflozin significantly slowed long-term eGFR decline in patients with CKD. The mean difference in eGFR slope between dapagliflozin- and placebo-treated patients was greater in patients with type 2 diabetes, with higher baseline HbA1c and higher UACR.

Funding

  • Commercial Support –