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Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348461/ https://www.ncbi.nlm.nih.gov/pubmed/36794422 http://dx.doi.org/10.1210/clinem/dgad088 |
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author | Biancalana, Edoardo Rossi, Chiara Raggi, Francesco Distaso, Mariarosaria Tricò, Domenico Baldi, Simona Ferrannini, Ele Solini, Anna |
author_facet | Biancalana, Edoardo Rossi, Chiara Raggi, Francesco Distaso, Mariarosaria Tricò, Domenico Baldi, Simona Ferrannini, Ele Solini, Anna |
author_sort | Biancalana, Edoardo |
collection | PubMed |
description | 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 time-control 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. |
format | Online Article Text |
id | pubmed-10348461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-103484612023-07-15 Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects Biancalana, Edoardo Rossi, Chiara Raggi, Francesco Distaso, Mariarosaria Tricò, Domenico Baldi, Simona Ferrannini, Ele Solini, Anna J Clin Endocrinol Metab Clinical Research Article 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 time-control 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. Oxford University Press 2023-02-16 /pmc/articles/PMC10348461/ /pubmed/36794422 http://dx.doi.org/10.1210/clinem/dgad088 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Research Article Biancalana, Edoardo Rossi, Chiara Raggi, Francesco Distaso, Mariarosaria Tricò, Domenico Baldi, Simona Ferrannini, Ele Solini, Anna Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects |
title | Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects |
title_full | Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects |
title_fullStr | Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects |
title_full_unstemmed | Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects |
title_short | Empagliflozin and Renal Sodium-Hydrogen Exchange in Healthy Subjects |
title_sort | empagliflozin and renal sodium-hydrogen exchange in healthy subjects |
topic | Clinical Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348461/ https://www.ncbi.nlm.nih.gov/pubmed/36794422 http://dx.doi.org/10.1210/clinem/dgad088 |
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