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Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial

BACKGROUND: The sodium/glucose cotransporter 2 inhibitor empagliflozin has cardiorenal protective properties through mechanisms beyond glucose control. In this study we assessed whether empagliflozin modifies renal oxygenation as a possible mechanism of renal protection, and determined the metabolic...

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Autores principales: Zanchi, Anne, Burnier, Michel, Muller, Marie‐Eve, Ghajarzadeh‐Wurzner, Arlène, Maillard, Marc, Loncle, Nicolas, Milani, Bastien, Dufour, Nathalie, Bonny, Olivier, Pruijm, Menno
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670540/
https://www.ncbi.nlm.nih.gov/pubmed/32567439
http://dx.doi.org/10.1161/JAHA.119.016173
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author Zanchi, Anne
Burnier, Michel
Muller, Marie‐Eve
Ghajarzadeh‐Wurzner, Arlène
Maillard, Marc
Loncle, Nicolas
Milani, Bastien
Dufour, Nathalie
Bonny, Olivier
Pruijm, Menno
author_facet Zanchi, Anne
Burnier, Michel
Muller, Marie‐Eve
Ghajarzadeh‐Wurzner, Arlène
Maillard, Marc
Loncle, Nicolas
Milani, Bastien
Dufour, Nathalie
Bonny, Olivier
Pruijm, Menno
author_sort Zanchi, Anne
collection PubMed
description BACKGROUND: The sodium/glucose cotransporter 2 inhibitor empagliflozin has cardiorenal protective properties through mechanisms beyond glucose control. In this study we assessed whether empagliflozin modifies renal oxygenation as a possible mechanism of renal protection, and determined the metabolic, renal, and hemodynamic effects of empagliflozin in nondiabetic subjects. METHODS AND RESULTS: In this double‐blind, randomized, placebo‐controlled study, 45 healthy volunteers underwent blood and urine sampling, renal ultrasound, and blood‐oxygenation‐level–dependent magnetic resonance imaging before and 180 minutes after administration of 10 mg empagliflozin (n=30) or placebo (n=15). These examinations were repeated after 1 month of daily intake. Cortical and medullary renal oxygenation were not affected by the acute or chronic administration of empagliflozin, as determined by 148 renal blood‐oxygenation‐level–dependent magnetic resonance imaging examinations. Empagliflozin increased glucosuria (24‐hour glucosuria at 1 month: +50.1±16.3 g). The acute decrease in proximal sodium reabsorption, as determined by endogenous fractional excretion of lithium (−34.6% versus placebo), was compensated at 1 month by a rise in plasma renin activity (+28.6%) and aldosterone (+55.7%). The 24‐hour systolic and diastolic ambulatory blood pressures decreased significantly after 1 month of empagliflozin administration (−5.1 and −2.0 mm Hg, respectively). Serum uric acid levels decreased (−28.4%), hemoglobin increased (+1.7%), and erythropoietin remained the same. CONCLUSIONS: Empagliflozin has a rapid and significant effect on tubular function, with sustained glucosuria and transient natriuresis in nondiabetic normotensive subjects. These effects favor blood pressure reduction. No acute or sustained changes were found in renal cortical or medullary tissue oxygenation. It remains to be determined whether this is the case in nondiabetic or diabetic patients with congestive heart failure or kidney disease. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03093103.
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spelling pubmed-76705402020-11-23 Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial Zanchi, Anne Burnier, Michel Muller, Marie‐Eve Ghajarzadeh‐Wurzner, Arlène Maillard, Marc Loncle, Nicolas Milani, Bastien Dufour, Nathalie Bonny, Olivier Pruijm, Menno J Am Heart Assoc Original Research BACKGROUND: The sodium/glucose cotransporter 2 inhibitor empagliflozin has cardiorenal protective properties through mechanisms beyond glucose control. In this study we assessed whether empagliflozin modifies renal oxygenation as a possible mechanism of renal protection, and determined the metabolic, renal, and hemodynamic effects of empagliflozin in nondiabetic subjects. METHODS AND RESULTS: In this double‐blind, randomized, placebo‐controlled study, 45 healthy volunteers underwent blood and urine sampling, renal ultrasound, and blood‐oxygenation‐level–dependent magnetic resonance imaging before and 180 minutes after administration of 10 mg empagliflozin (n=30) or placebo (n=15). These examinations were repeated after 1 month of daily intake. Cortical and medullary renal oxygenation were not affected by the acute or chronic administration of empagliflozin, as determined by 148 renal blood‐oxygenation‐level–dependent magnetic resonance imaging examinations. Empagliflozin increased glucosuria (24‐hour glucosuria at 1 month: +50.1±16.3 g). The acute decrease in proximal sodium reabsorption, as determined by endogenous fractional excretion of lithium (−34.6% versus placebo), was compensated at 1 month by a rise in plasma renin activity (+28.6%) and aldosterone (+55.7%). The 24‐hour systolic and diastolic ambulatory blood pressures decreased significantly after 1 month of empagliflozin administration (−5.1 and −2.0 mm Hg, respectively). Serum uric acid levels decreased (−28.4%), hemoglobin increased (+1.7%), and erythropoietin remained the same. CONCLUSIONS: Empagliflozin has a rapid and significant effect on tubular function, with sustained glucosuria and transient natriuresis in nondiabetic normotensive subjects. These effects favor blood pressure reduction. No acute or sustained changes were found in renal cortical or medullary tissue oxygenation. It remains to be determined whether this is the case in nondiabetic or diabetic patients with congestive heart failure or kidney disease. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03093103. John Wiley and Sons Inc. 2020-06-20 /pmc/articles/PMC7670540/ /pubmed/32567439 http://dx.doi.org/10.1161/JAHA.119.016173 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Zanchi, Anne
Burnier, Michel
Muller, Marie‐Eve
Ghajarzadeh‐Wurzner, Arlène
Maillard, Marc
Loncle, Nicolas
Milani, Bastien
Dufour, Nathalie
Bonny, Olivier
Pruijm, Menno
Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial
title Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial
title_full Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial
title_fullStr Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial
title_full_unstemmed Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial
title_short Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo‐Controlled Trial
title_sort acute and chronic effects of sglt2 inhibitor empagliflozin on renal oxygenation and blood pressure control in nondiabetic normotensive subjects: a randomized, placebo‐controlled trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670540/
https://www.ncbi.nlm.nih.gov/pubmed/32567439
http://dx.doi.org/10.1161/JAHA.119.016173
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