Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

• Published in: Journal of the American Society of Nephrology Vol. 32; no. 9; pp. 2352 - 2361
• Main Authors: Chertow, Glenn M, Vart, Priya, Jongs, Niels, Toto, Robert D, Gorriz, Jose Luis, Hou, Fan Fan, McMurray, John J V, Correa-Rotter, Ricardo, Rossing, Peter, Sjöström, C David, Stefánsson, Bergur V, Langkilde, Anna Maria, Wheeler, David C, Heerspink, Hiddo J L
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.09.2021
• Subjects: Aged; Benzhydryl Compounds - therapeutic use; Cardiovascular Diseases - epidemiology; Clinical Research; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetic Nephropathies - diagnosis; Diabetic Nephropathies - epidemiology; Female; Glomerular Filtration Rate; Glucosides - therapeutic use; Humans; Male; Middle Aged; Renal Insufficiency, Chronic - diagnosis; Renal Insufficiency, Chronic - epidemiology; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; stage 4 CKD; chronic kidney disease; SGLT2 inhibitor; dapagliflozin
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2021020167

In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized, placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in patients with CKD with or without type 2 diabetes. Adults with eGFR of 25-75 ml/min per 1.73 m and urinary albumin-to-creatinine ratio of 200-5000 mg/g had been randomized to receive dapagliflozin 10 mg/d or placebo. Here, we conducted a prespecified analysis of dapagliflozin's effects in patients with stage 4 CKD (eGFR,30 ml/min per 1.73 m ) at baseline. The primary end point was a composite of time to ≥50% sustained decline in eGFR, ESKD, or kidney or cardiovascular death. Secondary end points were a kidney composite (same as the primary end point but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. A total of 293 participants with stage 4 CKD received dapagliflozin and 331 received placebo. Patients with stage 4 CKD randomized to dapagliflozin experienced a 27% (95% confidence interval [95% CI]: -2 to 47%) reduction in the primary composite endpoint, and 29% (-2 to 51%), 17% (-53 to 55%), and 32% (-21 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-values were 0.22, 0.13, 0.63, and 0.95, respectively, comparing CKD stages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73 m per year in the dapagliflozin and placebo groups, respectively ( =0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Among patients with stage 4 CKD and albuminuria, the effects of dapagliflozin were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.