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- Title
Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects.
- Authors
Biancalana, Edoardo; Rossi, Chiara; Raggi, Francesco; Distaso, Mariarosaria; Tricò, Domenico; Baldi, Simona; Ferrannini, Ele; Solini, Anna
- Abstract
Context: Sodium glucose co-transporter-2 inhibitors exert clinically relevant cardiorenal protection. Among several mechanisms, inhibition of sodium-hydrogen exchanger-3 (NHE3) in proximal renal tubules has been proposed in rodents. Demonstration of this mechanism with the associated electrolyte and metabolic changes in humans is lacking. Objective: The present proof-of-concept study was designed to explore the involvement of NHE3 in modulating the response to sodium glucose co-transporter-2 inhibitors in humans. Methods: Twenty healthy male volunteers received 2 tablets of empagliflozin 25 mg during a standardized hydration scheme; freshly voided urines and blood samples were collected at timed intervals for 8 hours. Protein expression of relevant transporters was examined in exfoliated tubular cells. Results: Urine pH levels increased after empagliflozin (from 5.81 ± 0.5 to 6.16 ± 0.6 at 6 hours, P = .008) as did urinary output (from median, 1.7; interquartile range [IQR, 0.6; 2.5] to 2.5 [IQR, 1.7; 3.5] mL/min−1, P = .008) and glucose (from median, 0.03 [IQR, 0.02; 0.04] to 34.8 [IQR, 31.6; 40.2] %, P < .0001), and sodium fractional excretion rates (from median, 0.48 [IQR, 0.34; 0.65] to 0.71 [IQR, 0.55; 0.85] %, P = .0001), whereas plasma glucose and insulin concentrations decreased and plasma and urinary ketones increased. Nonsignificant changes in NHE3, phosphorylated NHE3, and membrane-associated protein 17 protein expression were detected in urinary exfoliated tubular cells. In a timecontrol study in 6 participants, neither urine pH nor plasma and urinary parameters changed. Conclusions: In healthy young volunteers, empagliflozin acutely increases urinary pH while inducing a substrate shift toward lipid utilization and ketogenesis, without significant changes in renal NHE3 protein expression.
- Subjects
EMPAGLIFLOZIN; GLUCOSE
- Publication
Journal of Clinical Endocrinology & Metabolism, 2023, Vol 108, Issue 8, pe567
- ISSN
0021-972X
- Publication type
Academic Journal
- DOI
10.1210/clinem/dgad088