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Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial

AIM: Sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) improve cardiorenal outcomes in patients with chronic kidney disease (CKD), with and without type 2 diabetes. The molecular mechanisms underlying these pleiotropic effects remain unclear, yet it is speculated that SGLT‐2i elicit a neurohormon...

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Autores principales: Antlanger, Marlies, Domenig, Oliver, Kaltenecker, Christopher C., Kovarik, Johannes J., Rathkolb, Vincent, Müller, Martin M., Schwaiger, Elisabeth, Hecking, Manfred, Poglitsch, Marko, Säemann, Marcus D., Kopecky, Chantal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305250/
https://www.ncbi.nlm.nih.gov/pubmed/34984822
http://dx.doi.org/10.1111/dom.14639
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author Antlanger, Marlies
Domenig, Oliver
Kaltenecker, Christopher C.
Kovarik, Johannes J.
Rathkolb, Vincent
Müller, Martin M.
Schwaiger, Elisabeth
Hecking, Manfred
Poglitsch, Marko
Säemann, Marcus D.
Kopecky, Chantal
author_facet Antlanger, Marlies
Domenig, Oliver
Kaltenecker, Christopher C.
Kovarik, Johannes J.
Rathkolb, Vincent
Müller, Martin M.
Schwaiger, Elisabeth
Hecking, Manfred
Poglitsch, Marko
Säemann, Marcus D.
Kopecky, Chantal
author_sort Antlanger, Marlies
collection PubMed
description AIM: Sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) improve cardiorenal outcomes in patients with chronic kidney disease (CKD), with and without type 2 diabetes. The molecular mechanisms underlying these pleiotropic effects remain unclear, yet it is speculated that SGLT‐2i elicit a neurohormonal modulation resulting in renin‐angiotensin system (RAS) activation. We hypothesized that combined SGLT‐2 and angiotensin‐converting enzyme inhibition (ACEi) favours RAS regulation towards the beneficial angiotensin‐(1‐7)‐driven axis. MATERIALS AND METHODS: This randomized controlled prospective study investigated the effect of 12 weeks treatment with the SGLT‐2i empagliflozin on top of ACEi on the molecular RAS dynamics in 24 diabetic and 24 non‐diabetic patients with CKD. Systemic RAS peptides were quantified by mass spectrometry. RESULTS: In patients with type 2 diabetes, combined SGLT‐2i and ACEi significantly upregulated plasma renin activity [pre‐treatment median and interquartile range 298.0 (43.0‐672.0) pmol/L versus post‐treatment 577.0 (95.0‐1543.0) pmol/L; p = .037] and angiotensin I levels [pre‐treatment 289.0 (42.0‐668.0) pmol/L versus post‐treatment 573.0 (93.0‐1522.0) pmol/L; p = .037], together with a significant increase of angiotensin‐(1‐7) levels [pre‐treatment 14.0 (2.1‐19.0) pmol/L versus post‐treatment 32.0 (5.7‐99.0) pmol/L; p = .012]. Empagliflozin treatment resulted in a 1.5 to 2‐fold increase in main RAS peptides in patients with diabetes compared with placebo. No significant effect of empagliflozin on top of ACEi on RAS peptides was found in patients with CKD without diabetes. CONCLUSION: A distinct RAS modulation by SGLT‐2i occurs in diabetic kidney disease reflected by enhancement of the beneficial angiotensin‐(1‐7) providing a molecular background for this renoprotective therapeutic approach.
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spelling pubmed-93052502022-07-28 Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial Antlanger, Marlies Domenig, Oliver Kaltenecker, Christopher C. Kovarik, Johannes J. Rathkolb, Vincent Müller, Martin M. Schwaiger, Elisabeth Hecking, Manfred Poglitsch, Marko Säemann, Marcus D. Kopecky, Chantal Diabetes Obes Metab Original Articles AIM: Sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) improve cardiorenal outcomes in patients with chronic kidney disease (CKD), with and without type 2 diabetes. The molecular mechanisms underlying these pleiotropic effects remain unclear, yet it is speculated that SGLT‐2i elicit a neurohormonal modulation resulting in renin‐angiotensin system (RAS) activation. We hypothesized that combined SGLT‐2 and angiotensin‐converting enzyme inhibition (ACEi) favours RAS regulation towards the beneficial angiotensin‐(1‐7)‐driven axis. MATERIALS AND METHODS: This randomized controlled prospective study investigated the effect of 12 weeks treatment with the SGLT‐2i empagliflozin on top of ACEi on the molecular RAS dynamics in 24 diabetic and 24 non‐diabetic patients with CKD. Systemic RAS peptides were quantified by mass spectrometry. RESULTS: In patients with type 2 diabetes, combined SGLT‐2i and ACEi significantly upregulated plasma renin activity [pre‐treatment median and interquartile range 298.0 (43.0‐672.0) pmol/L versus post‐treatment 577.0 (95.0‐1543.0) pmol/L; p = .037] and angiotensin I levels [pre‐treatment 289.0 (42.0‐668.0) pmol/L versus post‐treatment 573.0 (93.0‐1522.0) pmol/L; p = .037], together with a significant increase of angiotensin‐(1‐7) levels [pre‐treatment 14.0 (2.1‐19.0) pmol/L versus post‐treatment 32.0 (5.7‐99.0) pmol/L; p = .012]. Empagliflozin treatment resulted in a 1.5 to 2‐fold increase in main RAS peptides in patients with diabetes compared with placebo. No significant effect of empagliflozin on top of ACEi on RAS peptides was found in patients with CKD without diabetes. CONCLUSION: A distinct RAS modulation by SGLT‐2i occurs in diabetic kidney disease reflected by enhancement of the beneficial angiotensin‐(1‐7) providing a molecular background for this renoprotective therapeutic approach. Blackwell Publishing Ltd 2022-01-24 2022-05 /pmc/articles/PMC9305250/ /pubmed/34984822 http://dx.doi.org/10.1111/dom.14639 Text en © 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://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 Articles
Antlanger, Marlies
Domenig, Oliver
Kaltenecker, Christopher C.
Kovarik, Johannes J.
Rathkolb, Vincent
Müller, Martin M.
Schwaiger, Elisabeth
Hecking, Manfred
Poglitsch, Marko
Säemann, Marcus D.
Kopecky, Chantal
Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial
title Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial
title_full Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial
title_fullStr Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial
title_full_unstemmed Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial
title_short Combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial
title_sort combined sodium glucose co‐transporter‐2 inhibitor and angiotensin‐converting enzyme inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: results of a randomized, double‐blind, placebo‐controlled exploratory trial
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305250/
https://www.ncbi.nlm.nih.gov/pubmed/34984822
http://dx.doi.org/10.1111/dom.14639
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