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Updated: Jul 8, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD
Kaitlin J Mayne1,2, Natalie Staplin1, David F Keane3
1Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Significance Statement:
SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived "Fluid Overload" at recruitment. Empagliflozin induced a prompt and sustained reduction in "Fluid Overload," irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.
Background:
CKD is associated with fluid excess that 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 with placebo, the overall mean absolute "Fluid Overload" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L "Fluid Overload" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -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.
Trial Registration:
Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).
Insights
Empagliflozin significantly reduced fluid overload in chronic kidney disease (CKD) patients, measured by bioimpedance spectroscopy. This SGLT2 inhibitor treatment did not affect body fat mass, suggesting fluid shifts may contribute to its cardiovascular benefits.
Area of Science:
- Nephrology
- Cardiology
- Metabolic Diseases
Background:
- Chronic kidney disease (CKD) is often linked to fluid overload, detectable via bioimpedance spectroscopy.
- The precise mechanisms by which SGLT2 inhibitors benefit patients with CKD and cardiovascular disease remain under investigation.
Purpose of the Study:
- To evaluate the impact of sodium-glucose co-transporter 2 (SGLT2) inhibition with empagliflozin on bioimpedance-derived fluid overload and adiposity in individuals with CKD.
Main Methods:
- The EMPA-KIDNEY trial's bioimpedance substudy involved 660 CKD patients receiving either empagliflozin (10 mg daily) or a placebo.
- Bioimpedance measurements were taken at baseline, 2 months, and 18 months to assess absolute "Fluid Overload" (excess extracellular water) and fat mass.
Main Results:
- Empagliflozin treatment led to a statistically significant reduction in "Fluid Overload" by -0.24 L compared to placebo, sustained over 18 months.
- This reduction in fluid overload was consistent across various subgroups and included decreases in both extracellular and intracellular water.
- No significant changes in bioimpedance-derived fat mass or adipose tissue were observed with empagliflozin treatment.
Conclusions:
- Empagliflozin effectively and persistently reduces fluid overload in a diverse CKD population.
- The drug's impact on body water, rather than fat mass, may be a key factor in its cardiovascular protective effects in CKD patients.
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