Effects of empagliflozin on fluid overload, weight and blood pressure in chronic kidney disease

Mayne, K. J. et al. (2023) Effects of empagliflozin on fluid overload, weight and blood pressure in chronic kidney disease. Journal of the American Society of Nephrology, (doi: 10.1681/ASN.0000000000000271) (PMID:38082486) (Early Online Publication)

Abstract

Background: Chronic kidney disease (CKD) is associated with fluid excess which can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived “Fluid Overload” and adiposity in a CKD population. Methods: EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy’s primary outcome was the study-average difference in absolute “Fluid Overload” (an estimate of excess extracellular water) analyzed using a mixed-model repeated measures approach. Results: The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute “Fluid Overload” was 0.4±1.7 L. Compared to placebo, the overall mean absolute “Fluid Overload” difference among those allocated empagliflozin was -0.24 L (95%CI -0.38, -0.11), with similar-sized differences at 2- and 18-months, and in pre-specified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95%CI -0.69, -0.30, including the -0.24 L “Fluid Overload” difference); and a -0.30 L (95%CI -0.57, -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 [95%CI -1.41, 0.85] kg). The between-group difference in weight was -0.7 kg (95%CI -1.3, -0.1). Conclusions: In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

• Item Type: Articles
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Preiss, Dr David and Mark, Professor Patrick and Lees, Jennifer and Mayne, Dr Kaitlin
• Authors: Mayne, K. J., Staplin, N., Keane, D. F., Wanner, C., Brenner, S., Cejka, V., Stegbauer, J., Judge, P. K., Preiss, D., Emberson, J., Trinca, D., Dayanandan, R., Lee, R., Nolan, J., Omata, A., Green, J. B., Cherney, D. Z.I., Hooi, L. S., Pontremoli, R., Tuttle, K. R., Lees, J. S., Mark, P. B., Davies, S. J., Hauske, S. J., Steubl, D., Brückmann, M., Landray, M. J., Baigent, C., Haynes, R., and Herrington, W. G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of the American Society of Nephrology
• Publisher: American Society of Nephrology
• ISSN: 1046-6673
• ISSN (Online): 1533-3450
• Published Online: 12 December 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of the American Society of Nephrology 2023
• Publisher Policy: Reproduced under a Creative Commons License