Effects of Empagliflozin on Fluid Overload, Weight and Blood Pressure in Chronic Kidney Disease

Mayne, Kaitlin J; Staplin, Natalie; Keane, David F; Wanner, Christoph; Brenner, Susanne; Cejka, Vladimir; Stegbauer, Johannes; Judge, Parminder K; Preiss, David; Emberson, Jonathan; Trinca, Daniele; Dayanandan, Rejive; Lee, Ryonfa; Nolan, John; Omata, Akiko; Green, Jennifer B; Cherney, David ZI; Hooi, Lai Seong; Pontremoli, Roberto; Tuttle, Katherine R; Lees, Jennifer S; Mark, Patrick B; Davies, Simon J; Hauske, Sibylle J; Steubl, Dominik; Brückmann, Martina; Landray, Martin J; Baigent FMedSci, Colin; Haynes, Richard; Herrington, William G

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.

Citation

Mayne, K. J., Staplin, N., Keane, D. F., Wanner, C., Brenner, S., Cejka, V., …Herrington, W. G. (2023). Effects of Empagliflozin on Fluid Overload, Weight and Blood Pressure in Chronic Kidney Disease. Journal of the American Society of Nephrology, 35(2), 202-215. https://doi.org/10.1681/asn.0000000000000271

• Journal Article Type: Article
• Acceptance Date: Dec 12, 2023
• Online Publication Date: Dec 12, 2023
• Publication Date: Dec 12, 2023
• Deposit Date: Jan 8, 2024
• Journal: Journal of the American Society of Nephrology
• Print ISSN: 1046-6673
• Electronic ISSN: 1533-3450
• Publisher: American Society of Nephrology
• Peer Reviewed: Peer Reviewed
• Volume: 35
• Issue: 2
• Pages: 202-215
• DOI: https://doi.org/10.1681/asn.0000000000000271
• Keywords: BP; cardiovascular; CKD; clinical trial; diabetes; heart failure