@article{605619a4644440369b5288296c00e166,
title = "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",
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 substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that 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/1.73m2) 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.",
keywords = "acute kidney injury, chronic kidney disease, dapagliflozin, SGLT2 inhibitors",
author = "{DAPA-CKD Trial Committees and Investigators} and Heerspink, {Hiddo J.L.} and David Cherney and Douwe Postmus and Stef{\'a}nsson, {Bergur V.} and Chertow, {Glenn M.} and Dwyer, {Jamie P.} and Tom Greene and Mikhail Kosiborod and Langkilde, {Anna Maria} and McMurray, {John J.V.} and Ricardo Correa-Rotter and Peter Rossing and Sj{\"o}str{\"o}m, {C. David} and Toto, {Robert D.} and Wheeler, {David C.} and Glenn Chertow and Hou, {Fan Fan} and John McMurray and Robert Toto and Bergur Stefansson and Maffei, {L. E.} and P. Raffaele and Solis, {S. E.} and Arias, {C. A.} and D. Aizenberg and C. Luquez and C. Zaidman and N. Cluigt and M. Mayer and A. Alvarisqueta and A. Wassermann and R. Maldonado and J. Bittar and M. Maurich and Gaite, {L. E.} and N. Garcia and L. Sivak and Ramallo, {P. O.} and Santos, {J. C.} and {Garcia Duran}, R. and Oddino, {J. A.} and A. Maranon and Maia, {L. N.} and Avila, {D. D.} and Barros, {E. J.G.} and Vidotti, {M. H.} and D. Panarotto and Noronha, {I. D.L.} and Turatti, {L. A.A.} and J. Wada",
note = "Funding Information: The authors thank all investigators, trial teams, and patients for their participation in the trial. The authors thank David J Smeijer and Sjoukje van der Hoek for their assistance recording the precipitating factors for AKI. The authors acknowledge Nicola Truss and Marco Emanuele Favretto, from inScience Communications, London, UK, for assistance in editing and styling, preparation of figures, and submission of the manuscript—this support was funded by AstraZeneca. This study was funded by AstraZeneca. HJLH and DC were involved in the study design, conduct of the study, data analysis, and interpretation of the data; and they wrote the first draft of the manuscript. DCW, GMC, JJVM, TG, RC-R, PR, and RDT are members of the study's executive committee and were involved in the study design, data collection, and analysis/interpretation of the data. DP performed the data analyses. AML, CDS, and BVS were involved in the study design, conduct of the study, and interpretation of data. JPD was involved in data collection and interpretation. MK was involved in the interpretation of the data. All the authors reviewed the manuscript drafts for important intellectual content, provided approval of the final version for submission, and take responsibility for the accuracy and integrity of the data, including ensuring that any questions are appropriately investigated and resolved. HJLH is the guarantor and corresponding author, and as such accepts full responsibility for the overall content of the work and conduct of the study, had access to the data, and attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding Information: HJLH is consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Gilead, Janssen Pharmaceuticals, Merck, Mundipharma, Mitsubishi Tanabe, Novo Nordisk, and Retrophin; and has received research support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen Pharmaceuticals. DC has received honoraria from Boehringer Ingelheim, Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, AbbVie, Janssen Pharmaceuticals, Bayer, Prometic, Bristol Myers Squibb, and Novo Nordisk; and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen Pharmaceuticals, Sanofi, AstraZeneca, and Novo Nordisk. DP has nothing to declare. BVS, CDS, and AML are employees and stockholders of AstraZeneca. GMC has received fees from AstraZeneca for the DAPA-CKD trial steering committee, and research grants from the National Institute of Diabetes and Digestive and Kidney Diseases and Amgen; is on the board of directors for Satellite Healthcare; has received fees for advisory boards for Baxter, Cricket, DiaMedica, and Reata; holds stock options for Ardelyx, CloudCath, Durect, DxNow, and Outset; has received fees from Akebia, Sanifit, and Vertex for trial steering committees; and has received fees for Data Safety Monitoring Board service from Angion, Bayer, and ReCor. JPD has received fees from AstraZeneca for the conduct of this study; has received fees from Sanofi-Aventis and CSL Behring as part of a steering committee; has received fees from Novo Nordisk for outcome adjudication for a trial; has received fees from Goldfinch Bio, Birdrock Bio, and Boehringer Ingelheim for study design; and received personal fees from Bayer. TG has received grants for statistical consulting from AstraZeneca, CSL, and Boehringer Ingelheim; and personal fees from Janssen Pharmaceuticals, DURECT Corporation, and Pfizer for statistical consulting. MK reports receiving research grants from Boehringer Ingelheim and AstraZeneca; other research support from AstraZeneca; and honoraria from Boehringer Ingelheim, AstraZeneca, Sanofi, Amgen, Novo Nordisk, Merck (Diabetes), Janssen Pharmaceuticals, Bayer, GlaxoSmithKline, and Applied Therapeutics. JJVM reports payments to his employer, Glasgow University, for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Cardurion, Cytokinetics, GlaxoSmithKline, Novartis, Pfizer, and Theracos; and personal lecture fees from the Corpus, Abbott, Hickma, Sun Pharmaceuticals, and Medsca. RC-R has received honoraria from AstraZeneca, GlaxoSmithKline, Medtronic, and Boehringer Ingelheim; has lectured for Amgen, Janssen Pharmaceuticals, and Boehringer Ingelheim; and has received research support from GlaxoSmithKline, Novo Nordisk, and AstraZeneca. PR has received honoraria paid to Steno Diabetes Center Copenhagen for consultancy from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Sanofi, Eli Lilly, and research support from AstraZeneca and Novo Nordisk. RDT is a consultant for AstraZeneca, Amgen, Akebia, Quest Diagnostic, Bayer, Boehringer Ingelheim, Reata, and Relypsa. DCW provides ongoing consultancy services to AstraZeneca and has received honoraria and/or consultancy fees from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen Pharmaceuticals, Napp, Mundipharma, Merck Sharp and Dohme, Reata, Tricida, and Vifor Fresenius. Publisher Copyright: {\textcopyright} 2021 International Society of Nephrology",
year = "2022",
month = jan,
doi = "10.1016/j.kint.2021.09.005",
language = "English",
volume = "101",
pages = "174--184",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",
}