Steffen Flindt Nielsen, Camilla Lundgreen Duus, Niels Henrik Buus, Jesper Nørgaard Bech, Frank Holden Mose
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引用次数: 0
Abstract
Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) exert cardiorenal benefits in type 2 diabetes (T2D) and chronic kidney disease (CKD), possibly mediated by natriuresis and changes in fluid balance. We examined the effects of empagliflozin on fluid and electrolyte balance.
Methods: Employing a randomized, double-blind, placebo-controlled crossover design, we conducted three identical trials examining patients with T2D with and without CKD and non-diabetic CKD, respectively. A total of 49 participants were randomized to 4 weeks of empagliflozin 10 mg/day or matching placebo and crossed over to the opposite treatment after a wash-out. We measured body composition, 24-h ambulatory blood pressure (BP) and several markers of fluid and electrolyte balance.
Results: In the combined cohort, empagliflozin reduced extracellular body water by 0.29 l [95% confidence interval (CI) -0.54 to -0.03, P = .03] and tended towards reducing overhydration [-0.23 l (95% CI -0.51-0.05), P = .10]. Change in overhydration was correlated to changes in BP (R = 0.38, P = .008). Sodium excretion and urine volume was unchanged, but copeptin, a surrogate of antidiuretic hormone (ADH), increased by 30% (P > .0001), aquaporin-2 excretion increased by 8% (P = .04) and free water clearance decreased (P = .0001). Renin levels increased (P = .02) with non-significant increases in aldosterone (P = .05) and epithelial sodium channel excretion (P = .08).
Conclusion: SGLT2i could exert diuretic effects that, although compensated for by increased ADH and renin-angiotensin-aldosterone system activity, causes lasting changes in fluid balance.
Trial registration: EU Clinical Trials Register 2019-004303-12, 2019-004447-80 and 2019-004467-50.
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About the Journal
Clinical Kidney Journal: Clinical and Translational Nephrology (ckj), an official journal of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association), is a fully open access, online only journal publishing bimonthly. The journal is an essential educational and training resource integrating clinical, translational and educational research into clinical practice. ckj aims to contribute to a translational research culture among nephrologists and kidney pathologists that helps close the gap between basic researchers and practicing clinicians and promote sorely needed innovation in the Nephrology field. All research articles in this journal have undergone peer review.
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