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Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

Chertow, GM; Vart, P; Jongs, N; Toto, RD; Gorriz, JL; Hou, FF; McMurray, JJV; ... DAPA-CKD Trial Committees and Investigators, .; + view all (2021) Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. Journal of the American Society of Nephrology , 32 (9) pp. 2352-2361. 10.1681/ASN.2021020167. Green open access

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Abstract

BACKGROUND: 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. METHODS: Adults with eGFR of 25-75 ml/min per 1.73 m2 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 m2) 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. RESULTS: 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 m2 per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. CONCLUSIONS: 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.

Type: Article
Title: Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1681/ASN.2021020167
Publisher version: https://doi.org/10.1681/ASN.2021020167
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: SGLT2 inhibitor, chronic kidney disease, dapagliflozin, stage 4 CKD, Aged, Benzhydryl Compounds, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Glucosides, Humans, Male, Middle Aged, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10140986
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