Kidney Week

Abstract: SA-OR96

Efficacy and Safety of Dapagliflozin in Patients with CKD Stages 4-5

Session Information

• High-Impact Clinical Trials - 2
  October 26, 2024 | Location: Hall D, Convention Center
  Abstract Time: 12:00 PM - 12:15 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Hung, Chi-Chih, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Chi-Chih Hung, MD

• Chiu, Yi-Wen, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Yi-Wen Chiu, MD

• Hwang, Shang-Jyh, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Shang-Jyh Hwang, MD

Group or Team Name

• DAPA advKD Trial Investigators.

Background

Importance: Dapagliflozin improves renal outcome in patients with chronic kidney disease (CKD), but the effect of late initiating dapagliflozin when estimated glomerular filtration rate (eGFR) <25 mL/min/1.73m² remains uncertain.
Objective: To evaluate the efficacy and safety of dapagliflozin in patients with CKD stage 4 and 5.

Methods

Design: Dapagliflozin and Renal Surrogate Outcomes in Advanced Chronic Kidney Disease (DAPA advKD) trial (NCT05196347) was an investigator-led, randomized, open-label, trial designed to recruit 180 patients with eGFR 10-30 mL/min/1.73m² and eGFR decline ≥2.5 mL/min/1.73m²/yr.
Interventions: Patients were randomized 2:1 to dapagliflozin (5-10 mg/d) + integrated CKD care or integrated CKD care alone.
Main outcomes: The primary outcome was a preservation of eGFR decline ≥0.75 ml/min/1.73m²/yr. The 1^st secondary outcome (renal endpoint) was a composite of renal replacement therapy, eGFR <5 mL/min/1.73m², renal or cardiovascular (CV) death, or a >50% decline in eGFR. The 2^nd secondary outcome (renal and CV endpoint) was a composite of renal outcome as above, acute kidney injury (AKI) and heart failure. Predefined safety outcomes were measured.

Results

Over a median of 1.62 years, total eGFR slope (mL/min/1.73m²/yr) were -2.24 (-4.70 to -0.62) and -3.67 (-7.16 to -1.25) in the dapagliflozin and control groups, respectively; the primary outcome of eGFR slope difference was 1.06 (0.10 to 2.32) (p=0.019, linear mixed model). The secondary (renal) outcome occurred in 24/120 (20%) and 21/60 (35%) participants in the dapagliflozin and control groups, respectively (hazard ratio, 0.50 (0.28 to 0.89), p=0.019). The secondary (renal and CV) outcome occurred in 25/120 (21%) and 21/60 (35.0%) participants in the dapagliflozin and control groups, respectively (hazard ratio, 0.52 (0.29 to 0.93), p=0.028). There were higher incidence of AKI and heart failure in the control group, but higher incidence of eGFR dip in the dapagliflozin group. There was no difference of 5p- major adverse CV event and electrolyte imbalance.

Conclusion

Among patients with eGFR 10-30 mL/min/1.73m², the risks of eGFR decline and composite renal outcomes were lower with dapagliflozin than with control group.

Funding

• Other NIH Support – AstraZeneca