Effects of dapagliflozin in stage 4 chronic kidney disease

Glenn M. Chertow, Priya Vart, Niels Jongs, Robert D. Toto, Jose Luis Gorriz, Fan Fan Hou, John J.V. McMurray, Ricardo Correa-Rotter, Peter Rossing, C. David Sjöström, Bergur V. Stefánsson, Anna Maria Langkilde, David C. Wheeler, Hiddo J.L. Heerspink

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPACKD) 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 Adultswith eGFR of 25-75 ml/min per 1.73m2 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 patientswith stage 4 CKD (eGFR,30ml/min per 1.73m2) at baseline. The primary end pointwas 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]: 22 to 47%) reduction in the primary composite endpoint, and 29% (22 to 51%), 17% (253 to 55%), and 32% (221 to 61%) reductions in the kidney, cardiovascular and mortality endpoints, respectively, relative to placebo. Interaction P-valueswere 0.22, 0.13, 0.63, and 0.95, respectively, comparingCKDstages 4 versus 2/3. The eGFR slope declined by 2.15 and 3.38 ml/min per 1.73m2 per year in the dapagliflozin and placebo groups, respectively (P50.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Conclusions Among patientswith stage 4 CKD and albuminuria, the effects of dapagliflozinwere consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

Original languageEnglish (US)
Pages (from-to)2352-2361
Number of pages10
JournalJournal of the American Society of Nephrology
Volume32
Issue number9
DOIs
StatePublished - Sep 2021

ASJC Scopus subject areas

  • Nephrology

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