A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function

Heerspink, H. J.L. et al. (2022) A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function. Kidney International, 101(1), pp. 174-184. (doi: 10.1016/j.kint.2021.09.005) (PMID:34560136)

Abstract

This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high risk patients based on having chronic kidney disease (CKD) and severe albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m ) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.

• Item Type: Articles
• Keywords: Dapagliflozin, acute kidney injury, SGLT2 inhibitors, chronic kidney disease.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Heerspink, H. J.L., Cherney, D., Postmus, D., Stefánsson, B. V., Chertow, G. M., Dwyer, J. P., Greene, T., Kosiborod, M., Langkilde, A. M., McMurray, J. J.V., Correa-Rotter, R., Rossing, P., Sjöström, C. D., Toto, R. D., and Wheeler, D. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Kidney International
• Publisher: Elsevier
• ISSN: 0085-2538
• ISSN (Online): 1523-1755
• Published Online: 22 September 2021
• Copyright Holders: Copyright © 2021 International Society of Nephrology
• First Published: First published in Kidney International 101(1): 174-184
• Publisher Policy: Reproduced under a Creative Commons License