Quételet (body mass) index and effects of dapagliflozin in chronic kidney disease

Aim: To assess the effects of dapagliflozin in patients with chronic kidney disease (CKD) and albuminuria, with and without type 2 diabetes, stratified by the Quételet (body mass) index (BMI). Methods: We randomized 4304 adult patients with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73m² and urinary albumin-to-creatinine ratio of 200-5000 mg/g to dapagliflozin 10 mg/day or placebo. The primary outcome was a composite of sustained decline in eGFR of 50% or more, kidney failure, or death from kidney or cardiovascular causes. Secondary outcomes included kidney composite endpoint (primary composite endpoint without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure/ cardiovascular death), and all-cause mortality. We categorized participants according to World Health Organization BMI criteria: lean/ideal (<25 kg/m²), overweight (25-< 30 kg/m²), grade 1 obesity (30-<35 kg/m²), and grade 2/3 obesity (≥35 kg/m²). Results: Of 4296 (99.8%) randomized participants, 888 (20.7%), 1491 (34.7%), 1136 (26.4%), and 781 (18.2%) were categorized as lean/ideal, overweight, grade 1 obesity, and grade 2/3 obesity, respectively. Median follow-up was 2.4 years. Benefits of dapagliflozin were observed independent of baseline BMI for primary and secondary endpoints. Hazard ratios (95% CI) for dapagliflozin versus placebo 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 participants in the lean/ideal, overweight, grade 1 obesity, and grade 2/3 obesity groups (interaction P =.72). Conclusion: Among participants with CKD and albuminuria, with or without type 2 diabetes, kidney and cardiovascular benefits of dapagliflozin were evident and consistent across the BMI spectrum.