Kidney Week

Abstract: PO2366

Quételet (Body Mass) Index and Effects of Dapagliflozin in CKD

Session Information

• CKD: Insights from Recent Clinical Trials and Large Real-World Effectiveness Studies
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

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

Authors

• Chertow, Glenn Matthew, Stanford University School of Medicine, Stanford, California, United States

Glenn Matthew Chertow, MD, MPH, FASN

• Vart, Priya, University Medical Center Groningen, Groningen, Netherlands

Priya Vart,

• Langkilde, Anna Maria, AstraZeneca, Gothenburg, Sweden

Anna Maria Langkilde,

• McMurray, John, University of Glasgow, Glasgow, Glasgow, United Kingdom

John McMurray,

• Correa-Rotter, Ricardo, The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico

Ricardo Correa-Rotter,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

• Sjostrom, David, AstraZeneca, Gothenburg, Sweden

David Sjostrom,

• Stefansson, Bergur V., AstraZeneca, Gothenburg, Sweden

Bergur V. Stefansson,

• Toto, Robert D., UT Southwestern Medical Center, Dallas, Texas, United States

Robert D. Toto,

• Greene, Tom, University of Utah Health, Salt Lake City, Utah, United States

Tom Greene,

• Wheeler, David C., University College London, London, London, United Kingdom

David C. Wheeler,

• L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink,

Background

The DAPA-CKD trial (NCT03036150) demonstrated a reduction of the risk of kidney and cardiovascular (CV) events with dapagliflozin in patients with chronic kidney disease (CKD) and albuminuria with and without type 2 diabetes . We aimed to assess the effects of the SGLT2 inhibitor dapagliflozin in patients stratified by Quételet (body mass) index (BMI).

Methods

We randomized 4304 adult patients with estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73m² and urinary albumin-to-creatinine ratio 200–5000 mg/g to dapagliflozin 10 mg or placebo once daily. The primary outcome was a composite of sustained decline in eGFR of ≥50%, kidney failure, or death from kidney or CV causes. Secondary outcomes were a kidney composite endpoint, a CV composite endpoint, and all-cause mortality. We categorized patients according to World Health Organization criteria: lean or ideal (BMI <25 kg/m²), overweight (BMI 25 to <30 kg/m²), grade 1 obesity (BMI 30 to <35 kg/m²), and grade 2/3 obesity (BMI ≥35 kg/m²).

Results

Among 4296 (99.8%) randomized patients with available height and weight data, 888 (20.7%), 1491 (34.7%), 1136 (26.4%), and 781 (18.2%) were categorized as lean or ideal, overweight, grade 1 obesity, and grade 2/3 obesity, respectively. Hazard ratios (HRs) (dapagliflozin versus placebo) and 95% confidence intervals (CIs) for the primary composite endpoint were 0.60 (0.43–0.85), 0.55 (0.40–0.75), 0.71 (0.49–1.04), and 0.57 (0.37–0.87), among patients in the lean or ideal, overweight, grade 1 obesity, and grade 2/3 obesity groups (interaction p=0.72), respectively, indicating no significant heterogeneity in the dapagliflozin treatment effect. Corresponding HRs (95%CI) for the kidney composite endpoint: 0.55 (0.38–0.80), 0.54 (0.37–0.78), 0.51 (0.32–0.83), and 0.60 (0.36–0.98) (interaction p=0.98); CV composite endpoint: 0.88 (0.44–1.74), 0.72 (0.44–1.19), 0.94 (0.60–1.48), and 0.46 (0.27–0.77) (interaction p=0.21); and all-cause mortality: 0.78 (0.44–1.40), 0.51 (0.33–0.79), 0.98 (0.60–1.62), and 0.65 (0.36–1.18) (interaction p=0.27).

Conclusion

Among patients with CKD and albuminuria, with or without type 2 diabetes, kidney and CV benefits of dapagliflozin were evident across the spectrum of body size.

Funding

• Commercial Support – AstraZeneca