Quételet (body mass) index and effects of dapagliflozin in chronic kidney disease
Glenn M. Chertow, Priya Vart, Niels Jongs, Anna Maria Langkilde, John J.V. McMurray, Ricardo Correa‐Rotter, Peter Rossing, C. David Sjöström, Bergur V. Stefánsson, Robert D. Toto, David C. Wheeler, Hiddo J.L. Heerspink
Abstract
Abstract 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/1.73m 2 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/m 2 ), overweight (25‐< 30 kg/m 2 ), grade 1 obesity (30‐<35 kg/m 2 ), and grade 2/3 obesity (≥35 kg/m 2 ). 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.